WO2012135397A2 - Lactate-and ketones-induced gene signatures and use the same for diagnosing disease and predicting clinical outcome - Google Patents

Abstract

The present invention, at least in part, is directed to a method for discovering a biological marker (biomarker) of any cancer whose growth may be modulated by mitochondrial oxidative metabolism. In certain embodiments, the method comprises (a) contacting a set of at least one or more metabolites (e.g., 3-hydroxybutyrate or lactate or acetoacetate or oxaloacetate or citrate or a-ketoglutarate or glutamine or combinations thereof) to a first sample of a cancer cell line, a test cancer cell line; (b) assessing a level of gene expression pattern in the test cancer cell line; and (c) comparing the level of gene expression pattern of the test cancer cell line with a level of gene expression pattern in a second sample of the same cancer cell line not treated with the set of one or more metabolites, a control cancer cell line, whereby a difference between the level of the gene expression pattern in the test cancer cell line and the level of gene expression pattern in the control cancer cell line is a biomarker indicating mitochondrial oxidative metabolism in the cancer represented by the cancer cell.

Description

LACTATE- AND KETONES-INDUCED GENE SIGNATURES AND USE OF THE

SAME FOR DIAGNOSING DISEASE AND PREDICTING CLINICAL OUTCOME

FIELD OF THE INVENTION

[0100] This invention relates to the fields of oncology and medicine. More specifically, the invention provides biomarkers and methods of use thereof which aid the clinician in identifying those patients most likely to benefit from certain treatment regimens. The markers disclosed herein are also useful in assays to identify therapeutic agents useful for the treatment of malignancy.

BACKGROUND OF THE INVENTION [0101] The pharmaceutical industry spends billions worldwide on research and development of new drugs, but only a handful, 5 to 10%, of drugs entering the clinical phase of drug

development get approved for marketing. Consequently, the average cost per successful drug development program remains unacceptably high. This average cost per successful drug development is high in part because most of the invested capital spent per drug is related to drug failures along the pipeline development path.

[0102] An important reason for the high failure rate in clinical trials is the poor predictive value of currently used screening technologies for biological validation, pharmacological testing, and screening for success or failure of chemical entities and biologies in clinical trials involving human subjects. These screening technologies are based on in vitro cell-based screening models and in vivo animal models, which often lack or inadequately represent the clinical disease phenotype of the patients in which the tested chemical entities or biologies are intended to be used in the future. Therefore, success of these chemical entities or biologies in these models does not necessarily translate into clinical success in patients. Hence, the majority of chemical entities or biologies, while successful in these preceding screening and animal models, fail in clinical trials, particularly in late phase II and phase III trials (see, e.g., New Drug Development: A Regulatory Overview, Revised 5th edition. Ed. Mathieu M. Parexel, publishers). It has been estimated that more than 90% of new chemical entities (NCEs) fail in clinical trials, of which approximately two thirds fail for pharmacodynamic reasons (lack of efficacy and/or an unacceptable adverse event profile), the remaining third fail for pharmacokinetic reasons (see, e.g., Houlihan, Lokey, Howard& Zukin, Advanced Valuation Techniques in Life Sciences, February 2001).

DB1/ 69437₅16.1 [0103] Accordingly, many needs remain unmet in various aspects of drug development and disease treatment, including drug discovery, validation of candidate therapeutic targets, diagnosis and/or clinical classification of patients.

BRIEF SUMMARY OF THE INVENTION [0104] The invention provides, at least in part, biomarkers and methods of use thereof which aid the clinician in identifying those patients most likely to benefit from certain treatment regimens. The markers disclosed herein are also useful in assays to identify therapeutic agents useful for the treatment of malignancy, including breast cancer and prostate cancer.

[0105] In one aspect, the application discloses gene sets comprising genes which are differentially expressed in test samples derived from subjects having cancer, including subjects having different classes of cancer or subtypes of the same cancer, including subjects having different subtypes of breast cancer. In certain embodiments, the cancer subtypes are associated with different clinical outcomes or prognoses. Depending on the expression level of the genes in a test sample (derived from the cancer patients or from NCI-60 cell lines), the cancer (e.g., breast cancer) subtype is predicted to be associated with a good prognosis, a mixed prognosis or a poor prognosis. In alternative embodiments, the cancer subtypes are differentially associated with recurrence and/or metastasis and/or overall survival.

[0106] Accordingly, in one aspect, the application provides a method of diagnosing a cancer, including breast cancer, and/or a cancer subtype in a cancer patient. [0107] In another embodiment the application provides a method of providing a prognosis. In one embodiment, the method comprises (a) culturing cancer cells derived from a sample obtained from a cancer patient in the presence of a set of at least one high-energy metabolite; and (b) assessing gene expression levels in the cultured cancer cells; and (c) comparing the gene expression levels of the cancer cell culture with the gene expression levels in a control sample, whereby a difference between the gene expression levels in the cancer cell culture and the gene expression levels of the control cell culture is indicative of the clinical outcome. In one embodiment, the application provides a method of predicting or diagnosing recurrence. In another embodiment the application provides a method of predicting metastasis. In yet another embodiment the application provides a method of predicting decreased overall survival. [0108] In some embodiments, the application provides genes whose expression levels correlate to benign or malignant states in various cells and/or tissues, including the epithelial cells, including mammary epithelial cells (e.g., carcinoma), the bone, the muscle and other connective

DB 1/ 09437516.1 tissues (e.g., sarcoma), the lymphatic system (e.g., lymphoma), the blood cells and/or blood precursor cells (e.g., leukemia) and the pigment-providing cells (e.g., melanoma). In some embodiments the tumor cell is breast cancer tumor cell.

[0109] Another aspect of the present invention provides a method for selecting a therapeutic strategy for treating a cancer patient, the method comprising identifying a therapeutic agent which inhibits metabolite-induced gene expression pattern of at least a set of genes selected from those listed in at least one table from selected from Tables 1-7, wherein the set of genes are expressed cancer cells, derived from the cancer patient, cultured in the presence of at least one or more metabolites, wherein the therapeutic agent which inhibits metabolite-induced gene expression pattern is selected for treating the cancer patient.

[0110] A method for evaluating gene expression, the method comprising treating an in vitro culture of cancer cells with a set of at least one high-energy metabolite (such as ketones or lactate); and assessing changes in gene expression resulting from the treatment with said set of at least one high-energy metabolite; wherein said method comprises generating labeled

polynucleotide molecules corresponding to cancer genes having changes in expression resulting from the treatment with said set of at least one high-energy metabolite; and wherein said method further comprises applying said labeled molecules to a microarray having immobilized human genes to evaluate gene expression.

[0111] In an aspect, the present invention provides a method for identifying a set of at least one cancer associated gene, expression of which is induced by a set of at least one high-energy metabolite, the method comprising: (a) subjecting a cancer in vitro cell culture to treatment with the set of at least one high-energy metabolite; (b) thereafter assessing the level of gene expression in the cancer cell culture; and (c) comparing the level of gene expression in the cancer cell culture with the level of gene expression a control cell culture; whereby a difference between the level of gene expression in the cancer cell culture and the level of gene expression in the control cell culture is an indication that gene expression of the set of at least one cancer associated gene is induced by the set of at least one high-energy metabolite; wherein said method further comprises generating labeled polynucleotide molecules corresponding to the at least one cancer associated gene having changes in expression resulting from the treatment with said set of at least one high-energy metabolite, and wherein said method further comprises applying said labeled molecules to a microrray having immobilized human genes to identify the at least one cancer associated gene.

BRIEF DESCRIPTION OF THE DRAWINGS

DB l/ 69437516.1 [0112] Figure 1 : HeatMaps for the Intersection Between MCF7 Lactate-Induced Genes and Transcripts that are Highly Expressed in Neural Stem Cells;

[0113] Figure 2: HeatMaps for the Intersection Between MCF7 Ketone-Induced Genes and

Transcripts that are Highly Expressed in Hematopoietic Stem Cells;

[0114] Figure 3: Venn Diagrams for the Transcriptional Overlap between the Lactate-Induced and Ketone-Induced Transcriptional Profiles in MCF7 Cells;

[0115] Figure 4: HeatMaps for the Intersection Between MCF7 Lactate-Specific Genes and

Transcripts that are Highly Expressed in Poor Prognosis Cancers;

[0116] Figure 5: The Lactate-Induced Gene Signature Is Associated with ER(+) Breast Cancer and Predicts Poor Clinical Outcome;

[0117] Figure 6: The Ketone-Induced Gene Signature Is Associated with ER(+) Breast Cancer and Predicts Poor Clinical Outcome;

[0118] Figure 7: The Lactate-Induced Gene Signature Predicts Recurrence, Metastasis, and

Decreased Overall Survival in Luminal A Breast Cancers;

[0119] Figure 8: The Ketone-Induced Gene Signature Predicts Recurrence, Metastasis, and

Decreased Overall Survival in Luminal A Breast Cancers;

[0120] Figure 9: The Ketone- and Lactate-Induced "Stem Cell" Signatures Predict Decreased

Overall Survival in Luminal A Breast Cancers;

]0121] Figure 10: Survival Analysis for the Intersection Between MCF7 Lactate-Specific Genes and Transcripts that are Highly Expressed in Poor Prognosis Cancers;

[0122] Figure 11 : Lactate and Ketones Increase Histone Acetylation in MCF7 Cancer Cells.

MCF7 cells were treated with ketones and lactate;

[0123] Figure 12: Ketones and Lactate Promote the Growth of Mouse Embryonic Stem (ES)

Cells in Culture;

[0124] Figure 13: A New Metabolic Strategy for Personalized Cancer Diagnosis and Therapy;

and

[0125] Figure 14: Possible Mechanism(s) of Action of Ketones and Lactate: Converging on

Acetyl-CoA.

DB 1/ 69437516.1 DETAILED DESCRIPTION OF THE INVENTION

[0126] The present subject matter will now be described more fully hereinafter with reference to the accompanying Figures and Examples, in which representative embodiments are shown. The present subject matter can, however, be embodied in different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided to describe and enable one of skill in the art. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the subject matter pertains. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. [0127] Surprisingly, it has been discovered that a clinical outcome in cancer, in particular breast cancer, could be determined by epigenetics and energy metabolism, rather than by the accumulation of specific "classical" gene mutations. Thus, it is now possible, with the materials, procedures and methods described herein, to expedite discovery of: new cancer biomarkers, new therapeutic targets, leading to elucidation of oncogenic mechanisms; and to facilitate

classification of patients based on gene expression profile, disease prognosis and/or patients' therapeutic response.

[0128] It has been discovered that certain metabolites affect tumor cell behavior, including tumor-regenerating capacity and tumor progression. As any type of cell in the body can become a source of cancer, the tumor cell could be of any suitable cell type. Suitable tumor cell types include, but are not limited to those derived from, cancer of the epithelial cells (carcinoma), cancer of the bone, muscle or other connective tissues (sarcoma), cancer of the lymphatic system (lymphoma), cancer of blood cells or blood precursor cells (leukemia) and cancer of the pigment- providing cells (melanoma). In some embodiments the tumor cell is breast cancer tumor cell.

[0129] Tumor cells suitable for use with the methods disclosed can be derived from any cancer cells, including the NCI-60 cell lines having diverse tissue of origin: e.g., lung: NCI-H23, NCI- H522, A549-ATCC, EKVX, NCI-H226, NCI-H332M, H460, H0P62, and HOP92; colon: HT29, HCC-2998, HCT116, SW620, COLO205, HCT15, and KM12; breast: MCF7, MCF7ADRr, MDAMB231 , HS578T, MDAMB435, MDN, BT549, and T47D; ovarian: OVCAR3, OVCAR4, OVCAR5, OVCAR8, IGROV1, and SKOV3; leukemia: CCRFCEM, K562, MOLT4, HL60, RPMI8266, and SR; renal: U031, SN12C, A498, CAKI1, RXF393, 7860, ACHN, and TK10; melanoma: LOXIMVI, MALME3M, SKMEL2, SKMEL5, SKMEL28, M14, UACC62, and UACC257; prostate: PC3, DU145; CNS: SNB19, SNB75, U251, SF268, SF295, and SM539.

DB 1/ 69437516.1 [0130] Additional suitable rumor cells include: Non-Small Cell Lung (LXFL 529); Small Cell Lung (DMS 114, and SHP-77); Colon (DLD-1 and KM20L2); CNS (SNB-78, and XF 498); Melanoma (RPMI-7951 , and M19-MEL); Renal (RXF-631 and SN12K1); and Leukemia (P388, and P388/ADR). [0131] Traditionally, cancer classification has been based on histopathological and clinical data. New technologies, however, have enabled genome-wide analysis of gene expression patterns, which have suggested that individual cancer phenotypes, including leukemia and breast cancer, exhibit characteristic expression profiles (see, e.g. Golub T. R. et al. "Molecular classification of cancer: class discovery and class prediction by gene expression monitoring," Science 1999 (Wash. DC), 286, 531-537; and Gruvberger S. et al. "Estrogen receptor status in breast cancer is associated with remarkably distinct gene expression patterns," Cancer Res., 61 , 5979-5984).

[0132] Accordingly, in one aspect the present invention provides a new approach to personalized cancer medicine which incorporates features of both (i) cell metabolism and (ii) gene transcriptional profiling. In one embodiment a method is provided for identifying a mammalian cell as neoplastic or predisposed to neoplasia. The method comprising detecting metabolite-induced gene signature of a set of at least one or more genes listed in one or more of Tables 1-7 in a test cell derived from a sample obtained from a subject having cancer or suspected of having cancer. The test cell is identified as neoplastic or predisposed to neoplasia based on the detected level of the metabolite-induced gene signature(s).

[0133] Suitable metabolites include those derived from carbohydrates, fats and lipids and proteins. Suitable carbohydrates include monosaccharides, including include glucose (dextrose), fructose (levulose), galactose, xylose and ribose; disaccharides, including sucrose; and polysaccharides, including starch. [0134] Other suitable metabolites include various intermediary glycolysis products as well as end-products of glycololysis. These include: glucose-6-phosphate; fructose-6-phosphate;

fructose- 1,6-bisphosphate; fructose- 1 ,6-biphosphate; glycerone-phosphate (or dihydroxyacetone- phosphate); glyceraldehyde-3-P ("GAP"); glyceron-phosphate ("DHAP"); glycerate-1 ,3- biphosphate; glycrate-l ,3-biphosphate converted to 3-phosphoglycerate; glycerate-2 -phosphate; phosphoenolpyruvate; pyruvate; pyruvic acid; lactate; and lactic acid.

[0135] Other suitable metabolites includes glutamine and precursor compounds.

DBl/ 69437516.1 [0136] In an embodiment, the method for identifying a mammalian cell as neoplastic comprises detecting in a test mammalian cell (e.g. breast cancer cell) a level of gene expression pattern or activity, wherein the level of gene expression pattern or activity is induced by a set of at least one high-energy metabolite (e.g., 3-hydroxybutyrate or lactate); and identifying the test mammalian cell as neoplastic when a difference between the level of gene expression pattern or activity in the test mammalian cell and a corresponding level of gene expression pattern or activity in a control mammalian cell is detected.

[0137] At least two cancer models have been put forward to explain tumor heterogeneity and inherent differences of tumor-regenerating capacity (see, e.g., Visvader J. E. and Lindeman G. J. "Cancer stem cells in solid tumours: accumulating evidence and unresolved questions," Nat. Rev. Cancer. 2008, 8(10), 755-768). The clonal selection model of carcinogenesis implies that a random solitary cell undergoes malignant transformation, accumulates multiple mutations and subsequently acquires a survival advantage, which leads to clonal selection (see, e.g., Nowell P. C. "The clonal evolution of tumor cell populations," Science 1976, 194(4260), 23-28; and Campbell L. L. and Polyak K. "Breast tumor heterogeneity: cancer stem cells or clonal evolution?" Cell Cycle 2007, 6(19), 2332-2338). In contrast, the cancer stem cell ("CSC") hypothesis regards malignant transformation as a process, occurring in a subset of normal stem cells with pluripotent properties, which underlie deregulation of self-renewal pathways (see, e.g., Bonnet D. and Dick J. E. "Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell," Nat. Med. 1997, 3(7), 730-737; and Reya T. and Clevers H. "Wnt signalling in stem cells and cancer," Nature 2005, 434(7035), 843-850).

[0138] High energy metabolites, including glutamine, lactate and ketones, including 3- hydroxybutyrate, acetoacetate, possibly promote tumor cell growth and tumor metastasis in vivio (including experimental metastasis of human breast cancer cells (e.g., Michigan Cancer

Foundation-7 or MCF7) in in vivo xenograft models) by driving oxidative mitochondrial metabolism in cancer cells.

[0139] In order to understand how high energy metabolites affect tumor cell behavior, mechanistic experiments were conducted. In one experiment, MCF7 cells were cultured with lactate or ketones and then subjected to transcriptional analysis (exon-array). Transcriptional gene expressional analysis revealed differences in global gene expression profiles of tumor and normal cells. The results showed increased transcriptional expression of gene profiles normally associated with "sternness" (e.g., the ability of self-renew and differentiate), including genes upregulated in embryonic stem (ES) cells, demonstrating that the end-products of glycolysis (e.g., ketones and lactate) modulate tumor growth and metastasis.

DB1/¾437₅16.1 [0140] Accordingly, in one aspect of the present invention, the detection of inappropriate activation of sternness genetic pathways can be used to diagnose cancer and to predict the likelihood of therapy success or failure. Inappropriate activation of "sternness" genes in cancer cells is associated with aggressive clinical behavior and increased likelihood of poor clinical outcome in cancer patients, including therapy failure, recurrence of cancer, cancer metastasis and decreased survival, including overall survival. Thus, elucidation of such inappropriate activation of "sternness" gene expression can guide design of personalized medicine, wherein cancer therapy is specifically tailored to a patient's individual needs.

[0141] In another aspect of the present invention provides a method for growing stem cells. The method comprises culturing stem cells in a culture medium in presence of a set of at least one metabolite. In one embodiment, the metabolite is selected from the group consisting of glutamine, 3-hydroxybutyrate, acetoacetate and lactate.

[0142] Any type of stem cell can be used with the methods of the present invention. Suitable stem cells include mesenchymal stem cells, human embryonic stem cells, and the like. Human pluripotential cells can be created using in vitro fertilization technologies (human embryonic stem cells or HESC) (see, e.g. Thomson J. A et al. "Embryonic stem cell lines derived from human blastocysts," Science 1998, 282, 1 145-1147), from parthenogenesis the chemical activation of human oocytes (parthenogentically derived embryonic stem cells or PGESC) (see, e.g., Cibelli J. B. et al. "Parthenogenetic stem cells in nonhuman primates," Science 2002, 295, 819; and Vrana K. E. et al. "Nonhuman primate parthenogenetic stem cells," Proc. Natl. Acad. Sci. U S A 2003, 100 Suppl 1 , 11911-1 1916), from isolated human germ cells (primordial germ cells or PGC) (see, e.g., Shamblott M. J. et al. "Derivation of pluripotent stem cells from cultured human primordial germ cells," Proc Natl. Acad. Sci. USA 1998, 95, 13726-13731), or from human amniotic fluid (human amniotic fluid derived stem cells or HAFSC). [0143] In an embodiment, the neoplasm is breast cancer. Tissues in the body that are responsive to estrogens are called "estrogen-sensitive" or "estrogen-responsive" tissues and include cells of the urogenital tract, cardiovascular system and skeletal system. The cells that comprise estrogen-sensitive tissues contain estrogen receptors (ER). ER play significant roles in certain human disease states, breast cancer being one specific example. Cells in female breast tissue normally contain ER. Interaction of estrogens with ER in breast cells normally causes the breasts to grow at puberty and again during pregnancy. Since breast cells normally contain ER, it is not surprising that cells comprising tumors of the breast also contain ER. It has been estimated that 95% of all breast tumors, at least initially, have ER and are dependent on estrogens for growth. In such breast tumor cells, estrogens acting via the ER, dramatically escalate

DBl/ 69437516.1 ^{b J} proliferative and metastatic activity (Osborne, et al., 1980, Cancer, 46:2884-8). Moreover, ER (the estrogen or oestrogen receptor) negative breast tumours are general correlated with poorer prognosis than ER positive tumours (see, e.g., Baselga and Norton, Cancer Cell 2002, 1 , 319- 322). [0144] In another embodiment, a metabolite such as lactate or 3-hydroxybutyrate is administered to cultured cancer cells, and changes in gene expression resulting from said treatment with the metabolite (lactate or 3-hydroxybutyrate) are assessed. In another

embodiment, a ketone such as 3-hydroxybutyrate is administered to the cultured cancer cells, and changes in gene expression resulting from said treatment with the ketone are assessed. In another embodiment, the cancer cell cultures are exposed to a set of at least one or more metabolites of for about 12 hours to 48 hours. In yet another embodiment the level of gene expression is compared by transcriptional profiling following microarray analysis using a radio labeled probe. In yet another embodiment the levels of expression of a set at least 2000 to 5000 genes are compared. In another embodiment the level of expression of all the genes listed in Tables 1-7 are compared. In another embodiment the level of expression of a subset of all the genes listed in Tables 1-7 are compared.

[0145] In another aspect of the invention, a method is provided for reducing or inhibiting neoplastic growth of a mammalian cell which exhibits metabolite-induced transcription of a set at least one or more genes associated with a neoplasm. Expression of a polypeptide encoded by the metabolite-activated gene expression is reduced or inhibited in the mammalian cell by contacting the mammalian cell with a therapeutic agent that reduces or inhibits mitochondrial oxidative phosphorylation (e.g., an anti-oxidant). The set of genes is selected from those listed in Tables 1- 7. The growth of the cancer cells is reduced or inhibited through inhibition of upregulation of a set of at least one or more of the genes listed in Tables 1-7. [0146] Suitable therapeutic agents for use with the methods of the present invention include metformin and Monocarboxylate Transporter (MCT1) inhibitors, including AR-C117977 and AR-C155858 and pharmaceutically acceptable salts thereof. AR-C155858 has the following structural formula.

DB 1/ 69437516.1

[0147] Examples of suitable MCT1 inhibitors are disclosed in WO 2010/089580 (published 12 August 2010).

[0148] Adriamycin^® ( generic name: Doxorubicin; another brand name: Rubex^®) is another example of a therapeutic agent that can be used with the methods disclosed herein. Cancers that can be treated with Adriamycin^® include bladder, breast, head and neck, leukemia, liver, lung, lymphomas, mesothelioma, multiple myeloma, neuroblastoma, ovary, pancreas, prostate, sarcomas, stomach, testis (germ cell), thyroid and uterus.

[0149] Another aspect of the invention provides a method for selecting a therapeutic strategy for treating a cancer patient. A set of one or more genes selected from those listed in Tables 1-7, whose expression in cancer cells of the patient is inhibited by an agent that reduces or inhibit oxidative mitochondrial metabolism is identified. A therapeutic agent which inhibits expression of the set of at least one or more genes is selected for treating the cancer patient.

[0150] In another aspect, the invention pertains to a method for evaluating gene expression wherein said method comprises treating an in vitro culture of cancer cells with a set of at least one high-energy metabolite (such as ketones or lactate); and assessing changes in gene expression resulting from the treatment with said set of at least one high-energy metabolite; wherein said method comprises generating labeled polynucleotide molecules corresponding to cancer genes having changes in expression resulting from the treatment with said set of at least one high-energy metabolite; and wherein said method further comprises applying said labeled molecules to a microarray having immobilized human genes to evaluate gene expression.

[0151] In an embodiment, a set of at least one high-energy metabolite is selected from ketones and lactate. In another embodiment the in vitro culture of cancer cells is treated with the set of at least one high-energy metabolite for about 2 to 12 hours. In another embodiment the in vitro

DB 1/ 69437516.1 culture of cancer cells is treated with the set of at least one high-energy metabolite for about 12 hours.

[0152] In another aspect, the present invention provides a method for identifying a set of at least one cancer associated gene, expression of which is induced by a set of at least one high- energy metabolite, the method comprising: (a) subjecting a cancer in vitro cell culture to treatment with the set of at least one high-energy metabolite; (b) thereafter assessing the level of gene expression in the cancer cell culture; and (c) comparing the level of gene expression in the cancer cell culture with the level of gene expression a control cell culture, whereby a difference between the level of gene expression in the cancer cell culture and the level of gene expression in the control cell culture is an indication that gene expression of the set of at least one cancer associated gene is induced by the set of at least one high-energy metabolite; wherein said method further comprises generating labeled polynucleotide molecules corresponding to the at least one cancer associated gene having changes in expression resulting from the treatment with said set of at least one high-energy metabolite, and wherein said method further comprises applying said labeled molecules to a microrray having immobilized human genes to identify the at least one cancer associated gene.

[0153] In accordance with the present invention, there is provided a method for predicting a clinical outcome in a cancer patient, comprising (a) culturing cancer cells derived from a sample obtained from a cancer patient in the presence of a set of at least one high-energy metabolite; and (b) assessing gene expression levels in the cultured cancer cells; and (c) comparing the gene expression levels of the cancer cell culture with the gene expression levels in a control sample, whereby a difference between the gene expression levels in the cancer cell culture and the gene expression levels of the control cell culture is indicative of the clinical outcome.

[0154] In an embodiment, the clinical outcome is prognosis for survival. In alternative embodiments, the prognosis is a poor clinical outcome (e.g., shorter survival). In certain embodiments the poor clinical outcome is recurrence of cancer, increased/shorter survival of cancer, and/or cancer progression in the cancer patient. In alternative embodiments the clinical outcome is increased or decreased overall survival.

[0155] In accordance with another aspect, the present invention provides a method of stratifying a subject or a group of subjects having a cancer for a clinical trial, the method comprising: (a) treating an in vitro culture of cancer cells derived from a biological sample obtained from the subject or each member of the group of subjects having cancer with a set of at least one high-energy metabolite (such as ketones or lactate); (b) assessing changes in gene

DBl/ 69437516.1 expression induced by said set of at least one high-energy metabolite; (c) comparing the level of gene expression in the in vitro culture of cancer cells with a level of gene expression in a control cell culture; and (d) stratifying the subject or the group of subjects for a clinical trial on the basis of a difference between the level of gene expression in the in vitro culture of cancer cells and the level of gene expression in the control cell culture.

[0156] Those of ordinary skill in the art will be familiar with a variety of methods for assessing gene expression levels in tissue and/or biological fluid samples. In certain embodiments, assessing gene expression levels comprises (a) subjecting a spatially discrete microregion of an intact tissue sample to one or more physical or chemical treatments; and (b) assessing the gene expression levels in a nucleic acid sample from the microregion. If two or more spatially discrete microregions are assessed, then the gene expression levels of the different microregions may be compared. Assessing may also comprise immunologic detection of a gene or gene product (e.g., protein) or quantitative detection of an RNA (e.g., quantitative RT-PCR, Northern blotting) encoding a gene product (e.g., protein). [0157] As will be appreciated by those of skill in the art, proteomics techniques can be used analyze and define the biomarkers of the present invention. In other words, instead of gene expression profiling can be conducted in terms of proteins, the products of the expressed genes. Accordingly, in certain embodiments, proteomics can be used to discover suitable biomarkers for use with the present invention. Proteomics is, among other things, the study of the proteome, the protein complement of the genome. The term proteome is also used to refer to the totality of the proteins present in a sample (e.g. tissue, organism, or cell culture) at a certain point of time. Proteomics includes, among other things, study of the global changes of protein expression in a sample (also referred to as "expression proteomics")- Proteomics typically includes the following steps: (1) separation of individual proteins in a sample by 2-D gel electrophoresis (2-D PAGE); (2) identification of the individual proteins recovered from the gel, e.g. by mass spectrometry and/or N-terrninal sequencing, and (3) analysis of the data using bioinformatics. Proteomics methods are valuable supplements to other methods of gene expression profiling, and can be used, alone or in combination with other methods of the present invention, to detect the biomarkers of the present invention. I. Definitions

[0158] As used herein, the following terms have the meanings ascribed to them unless specified otherwise. The term "cancer" is intended to include any member of a class of diseases characterized by the uncontrolled growth of aberrant cells. The term includes all known cancers

DB 1/ 69437516.1 and neoplastic conditions, whether characterized as malignant, benign, soft tissue, or solid, and cancers of all stages and grades including pre- and post-metastatic cancers. Examples of different types of cancer include, but are not limited to, lung cancer (e.g., non-small cell lung cancer); digestive and gastrointestinal cancers such as colorectal cancer, gastrointestinal stromal tumors, gastrointestinal carcinoid tumors, colon cancer, rectal cancer, anal cancer, bile duct cancer, small intestine cancer, and stomach (gastric) cancer; esophageal cancer; gallbladder cancer; liver cancer; pancreatic cancer; appendix cancer; breast cancer; ovarian cancer; renal cancer (e.g., renal cell carcinoma); cancer of the central nervous system; skin cancer;

lymphomas; choriocarcinomas; head and neck cancers; osteogenic sarcomas; and blood cancers. As used herein, a "tumor" comprises one or more cancerous cells.

[0159] As used herein, the term "profile" includes any set of data that represents the distinctive features or characteristics associated with a tumor, tumor cell, and/or cancer. The term encompasses a "nucleic acid profile" that analyzes one or more genetic markers, a "protein profile" that analyzes one or more biochemical or serological markers, and combinations thereof. Examples of nucleic acid profiles include, but are not limited to, a genotypic profile, gene copy number profile, gene expression profile, DNA methylation profile, and combinations thereof. Non-limiting examples of protein profiles include a protein expression profile, protein activation profile, and combinations thereof. For example, a "genotypic profile" includes a set of genotypic data that represents the genotype of one or more genes associated with a tumor, tumor cell, and/or cancer. Similarly, a "gene copy number profile" includes a set of gene copy number data that represents the amplification of one or more genes associated with a tumor, tumor cell, and/or cancer. Likewise, a "gene expression profile" includes a set of gene expression data that represents the mRNA levels of one or more genes associated with a tumor, tumor cell, and/or cancer. In addition, a "DNA methylation profile" includes a set of methylation data that represents the DNA methylation levels (e.g., methylation status) of one or more genes associated with a tumor, tumor cell, and/or cancer. Furthermore, a "protein expression profile" includes a set of protein expression data that represents the levels of one or more proteins associated with a tumor, tumor cell, and/or cancer. Moreover, a "protein activation profile" includes a set of data that represents the activation (e.g., phosphorylation status) of one or more proteins associated with a tumor, tumor cell, and/or cancer.

[0160] With regard to nucleic acids used in the invention, the term "isolated nucleic acid" is sometimes employed. This term, when applied to DNA, refers to a DNA molecule that is separated from sequences with which it is immediately contiguous (in the 51 and 3' directions) in the naturally occurring genome of the organism from which it was derived. For example, the

DB 1/ 69437516.1 "isolated nucleic acid" may comprise a DNA molecule inserted into a vector, such as a plasmid or virus vector, or integrated into the genomic DNA of a prokaryote or eukaryote. An "isolated nucleic acid molecule" may also comprise a cDNA molecule. An isolated nucleic acid molecule inserted into a vector is also sometimes referred to herein as a recombinant nucleic acid molecule.

[0161] For purposes of the present invention, "a" or "an" entity refers to one or more of that entity; for example, "a cDNA" refers to one or more cDNA or at least one cDNA. As such, the terms "a" or "an," "one or more" and "at least one" can be used interchangeably herein. It is also noted that the terms "comprising," "including," and "having" can be used interchangeably. Furthermore, a compound "selected from the group consisting of refers to one or more of the compounds in the list that follows, including mixtures (i.e. combinations) of two or more of the compounds. According to the present invention, an isolated, or biologically pure molecule is a compound that has been removed from its natural milieu. As such, "isolated" and "biologically pure" do not necessarily reflect the extent to which the compound has been purified. An isolated compound of the present invention can be obtained from its natural source, can be produced using laboratory synthetic techniques or can be produced by any such chemical synthetic route.

[0162] The term "oligonucleotide," as used herein is defined as a nucleic acid molecule comprised of two or more ribo- or deoxyribonucleotides, preferably more than three. The exact size of the oligonucleotide will depend on various factors and on the particular application and use of the oligonucleotide. Oligonucleotides, which include probes and primers, can be any length from 3 nucleotides to the full length of the nucleic acid molecule, and explicitly include every possible number of contiguous nucleic acids from 3 through the full length of the polynucleotide. Preferably, oligonucleotides are at least about 10 nucleotides in length, more preferably at least 15 nucleotides in length, more preferably at least about 20 nucleotides in length.

[0163] The term "probe" as used herein refers to an oligonucleotide, polynucleotide or nucleic acid, either RNA or DNA, whether occurring naturally as in a purified restriction enzyme digest or produced synthetically, which is capable of annealing with or specifically hybridizing to a nucleic acid with sequences complementary to the probe. A probe may be either single-stranded or double-stranded. The exact length of the probe will depend upon many factors, including temperature, source of probe and use of the method. For example, for diagnostic applications, depending on the complexity of the target sequence, the oligonucleotide probe typically contains 15-25 or more nucleotides, although it may contain fewer nucleotides. The probes herein are selected to be complementary to different strands of a particular target nucleic acid sequence.

DB 1/ 69437516.1 This means that the probes must be sufficiently complementary so as to be able to "specifically hybridize" or anneal with their respective target strands under a set of pre-determined conditions. Therefore, the probe sequence need not reflect the exact complementary sequence of the target. For example, a non-complementary nucleotide fragment may be attached to the 5' or 3' end of the probe, with the remainder of the probe sequence being complementary to the target strand.

Alternatively, non-complementary bases or longer sequences can be interspersed into the probe, provided that the probe sequence has sufficient complementarity with the sequence of the target nucleic acid to anneal therewith specifically.

[0164] The term "primer" as used herein refers to an oligonucleotide, either R A or DNA, either single-stranded or double-stranded, either derived from a biological system, generated by restriction enzyme digestion, or produced synthetically which, when placed in the proper environment, is able to functionally act as an initiator of template-dependent nucleic acid synthesis. When presented with an appropriate nucleic acid template, suitable nucleoside triphosphate precursors of nucleic acids, a polymerase enzyme, suitable cofactors and conditions such as a suitable temperature and H, the primer may be extended at its 3' terminus by the addition of nucleotides by the action of a polymerase or similar activity to yield a primer extension product. The primer may vary in length depending on the particular conditions and requirement of the application. For example, in diagnostic applications, the oligonucleotide primer is typically 15-25 or more nucleotides in length. The primer must be of sufficient complementarity to the desired template to prime the synthesis of the desired extension product, that is, to be able anneal with the desired template strand in a manner sufficient to provide the 3' hydroxyl moiety of the primer in appropriate juxtaposition for use in the initiation of synthesis by a polymerase or similar enzyme. It is not required that the primer sequence represent an exact complement of the desired template. For example, a non-complementary nucleotide sequence may be attached to the 51 end of an otherwise complementary primer. Alternatively, non- complementary bases may be interspersed within the oligonucleotide primer sequence, provided that the primer sequence has sufficient complementarity with the sequence of the desired template strand to functionally provide a template -primer complex for the synthesis of the extension product. II. Detection Of Biomarkers

[0165] The biomarkers of this invention can be detected by any suitable method. Detection paradigms that can be employed to this end include optical methods, electrochemical methods (voltametry and amperometry techniques), atomic force microscopy, and radio frequency methods, e.g., multipolar resonance spectroscopy. Illustrative of optical methods, in addition to

DB 1/ 69437516.1 microscopy, both confocal and non-confocal, are detection of fluorescence, luminescence, chemiluminescence, absorbance, reflectance, transmittance, and birefringence or refractive index (e.g., surface plasmon resonance, ellipsometry, a resonant mirror method, a grating coupler waveguide method or interferometry). [0166] In certain embodiments of the present invention genetic events such as altered gene expression level and alternative splicing are detected. Common detection methods include gene- and exon-level expression and exon-level expression. In particular, Affymetrix GeneChip® Exon Arrays can be used to examine alternative splicing. Affymetrix GeneChip® 3' Expression Arrays, Exon Array, Promoter Tiling Arrays and Whole-Genome Tiling Arrays all can be used to examine altered gene expression level.

[0167] III. Gene Expression Profiling

[0168] A gene expression profile is typically evaluated in vitro on a sample collected from a subject in comparison to a normal or reference sample. Determination of a transcriptional expression profile can be accomplished, e.g., using hybridization techniques well-known to those skilled in the art such as Northern analysis and slot blot hybridization or by performing reverse- transcriptase (RT)-PCR amplification followed by gel electrophoresis. Applicable PCR amplification techniques are described in Ausubel et al., Current Protocols in Molecular Biology, John Wiley & Sons, Inc., New York (1999); Theophilus et al., "PCR Mutation Detection Protocols," Humana Press (2002); and Innis et al., "PCR Applications: Protocols for Functional Genomics," 1st Edition, Academic Press (1999). General nucleic acid hybridization methods are described in Anderson, "Nucleic Acid Hybridization," BIOS Scientific Publishers (1999).

Amplification or hybridization of a plurality of transcribed nucleic acid sequences (e.g., mRNA or cDNA) can also be performed using mRNA or cDNA sequences arranged in a microarray. Microarray methods are generally described in Hardiman, "Microarrays Methods and

Applications: Nuts & Bolts," DNA Press (2003) and Baldi et al., "DNA Microarrays and Gene Expression: From Experiments to Data Analysis and Modeling," Cambridge University Press (2002).

[0169] The measurement of gene expression profiles using microarrays also has many important applications to the monitoring of disease states and therapies, the identification of drug targets, the identification of pathways of drug action, and drug design. In particular,

measurement of gene expression profiles using microarrays can be used to identify "good prognosis" and "poor prognosis" gene expression signatures, which can be used to predict the clinical outcome of cancer patients, including breast cancer patients. The microarray gene

DB l/ 69437516.1 expression profiles can also be used to evaluate the target specificity of a candidate drug by comparison of an expression profile obtained from cells treated with the candidate drug to a database of expression profiles obtained from cells treated with known drugs (see, e.g., U.S. Patent No. 5,777,888). [0170] Comparing patterns of gene expression is a widely used means of identifying novel genes, investigating gene function, and finding potential new therapeutic targets (see, e.g., Shiue et al., Drug Devel. Res. 1997, 41 ,142-159). Many techniques have been used to identify and clone differentially expressed genes (see, e.g., Liang et al. Science 1992, 257, 967-971 ; Welsh et al. Nucleic Acids Res. 1992, 20, 4965-4970; Tedder et al. Proc. Natl. Acad. Sci. 1988, 85, 208- 212; Davis et al. Proc. Natl. Acad. Sci. 1984, 81, 2194-2198; Lisitsyn et al. Science 1993,

259:946-951 ; Velculescu et al. Science 1995, 270:484-487; Diatchenko et al. Proc. Natl. Acad. Sci. 1996, 93, 6025-6030; Jiang et al., Proc. Natl. Acad. Sci. 2000, 97,12684-12689; Yang et al. Nucleic Acids Res. 1999, 27, 517-523).

[0171] Other techniques, including cDNA microarray hybridization have been used to quantify the expression of many thousands of discrete mRNA or cDNA sequences in a single assay known as expression profiling (see, e.g., van't Veer et al. Nature 2002, 415, 530-536; Hughes et al. Nature Biotech. 2001, 19, 342-347; Hughes et al. Cell 2000, 102,109-126; Lockhart and Winzeler, Nature 2000, 405, 827-836; Roberts et al. Science 2000, 287, 873-880; Wang et al. Gene 1999, 229, 101-108; Lockhart et al. Nat. Biotech. 1996, 14, 1675-1680; Schena et al.

Science 1995, 270, 467-470; and U.S. Patent No. 6,040,138). For example, EGFR mRNA levels can be measured in tumor samples by microarray hybridization as described in Bhargava et al., Mod. Pathol. 2005, 18,1027-1033. In certain embodiments, a gene expression microarray groups genes according to similarities in patterns of gene expression in expression profiling experiments.

[0172] In addition, gene expression profiles can be used to identify pathway-specific reporters and target genes for a particular biological pathway of interest. Such reporter genes and probes directed to them can be used to measure the activity of a particular biological pathway and may be further used in the design of drugs, drug therapies, or other biological agents to target a particular biological pathway. Gene expression profiles can also be used to determine protein activity levels of a target protein using the methods described in U.S. Patent No. 6,324,479. IV. EXAMPLES

[0173] Example 1: Culture of MCF7 Cells and Treatment with Lactate and Ketones:

DB 1/ 69437₅16.1 The estrogen receptor positive ceil line MCF7 was purchased from ATCC. Cells were maintained in DMEM, with 10% Fetal Bovine Serum (FBS) and Penicillin 100 units/mL- Streptomycin 100 μg/mL (Invitrogen) [DMEM 10% FBS-Pen-Strep]. Cells were cultured in a humidified atmosphere containing 5% C02 at 37°C. Briefly, 1.4 x 10⁶ MCF7 cells were plated in 10 cm plastic dishes (Corning) in DMEM 10% FBS-Pen-Strep. After 24 hours, the media of these cells was changed to DMEM with 10% NuSerum (a low protein alternative to FBS; BD Biosciences) and Pen-Strep with or without 10 mM L-lactate (sodium salt; Sigma cat. #71718), or 10 mM R-3- hydroxy-butyrate (sodium salt; Sigma cat. #298360). Cells were maintained in this media for 48 hours before gene expression profiling was performed. Acetylation-specific antibodies directed against histone proteins were obtained from Cell Signaling Technology, Inc.

[0174] Example 2: Genome-wide Transcriptional Profiling (Exon-arrav):

Total RNA was extracted using the RNeasy protocol from Qiagen (Valencia, California, USA). RNA was prepared from three control MCF7 samples, and three MCF7 samples treated with lactate, and three MCF7 samples treated with ketones. RNA quality was evaluated using the Agilent 2100 Bioanalyzer (Agilent, Palo Alto, California, USA). RNA amplification and labeling was performed from 50 ng total RNA by the WT-Ovation Pico RNA amplification system (NuGen Technologies, Inc.). Amplified cDNA was purified with QIAGEN QIAquick PCR purification Kit. Sense transcript cDNA (ST-cDNA) was generated from 3 μ% amplified cDNA using WT-Ovation Exon module (NuGen Technologies, Inc.). Purified ST-cDNA was assed for yield using the Nanodrop Spectrophotometer (NanoDrop Technologies, Inc.). 5 g ST-cDNAs were fragmented and chemically labeled with biotin to generate biotinylated ST-cDNA using FL- Ovation cDNA biotin module V2 (NuGen Technologies, Inc.). Each Affymetrix Human Exon (HuEx-1.0-st-v2) array (Affymetrix, Santa Clara, CA) were hybridized with fragmented and biotin-labeled target (4.5 μg) in 200 μΐ of hybridization cocktail. Target denaturation was performed at 99°C for 2 min. and then 45°c for 5 min., followed by hybridization for 18 hrs. Arrays then were washed and stained using Genechip Fluidic Station 450, and hybridization signals were amplified using antibody amplification with goat IgG (Sigma- Aldrich) and anti- streptavidin biotinylated antibody (Vector Laboratories, Burlingame, CA, USA). Chips were scanned on an Affymetrix Gene Chip Scanner 3000, using Command Console Software.

Background correction and normalization were done using Robust Multichip Average (RMA) with Genespring V 11.5 software (Agilent, Palo Alto, CA, USA). Results from one exon for each gene analyzed were selected for inclusion in Supplemental Tables 1 and 2. A p-value of <0.05 was considered statistically significant.

[0175] Example 3: Analysis of Clinical Outcome in Human Breast Cancer Patients:

DB 1/ 69437516.1 A microarray dataset that was previously compiled from the public repositories Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo/)⁴⁸ and ArrayExpress

(http://www.ebi.ac.uk/arrayexpress/) ⁴⁹ was used to evaluate the Ketone and Lactate expression signatures in the context of clinical samples ⁵⁰' ⁵¹. Only samples with ER IHC data were selected for analysis, including 967 ER-positive and 325 ER-negative, for a total of 1292 samples.

Samples were first analyzed in subsets based on their ER IHC status. Additional subsets were defined by classifying samples among five canonical breast cancer subtypes, including luminal A, luminal B, normal-like, basal, and Her-2-overexpressing disease. Samples were classified by computing their correlation against five expression profile centroids representing these breast cancer subtypes and assigning and assigning them to the subtype with the highest corresponding correlation coefficient ⁵². Samples with a maximum correlation coefficient below 0.3 were considered unclassified. Differential expression of the averaged gene signature magnitude among these sample subsets was evaluated using two-tailed t-test. Kaplan-meier analysis was used to evaluate survival trends within sample subsets, including 627 samples with metastasis- free survival time (507 ER-pos., 120 ER-neg.), 637 with relapse free survival time (517 ER-pos., 120 ER-neg.), and 329 with overall survival time (219 ER-pos., 110 ER-neg.). The Log-rank test was used to evaluate differences in survival curves for high vs. low signature-expressing populations.

[0176] Example 4: Murine Embryonic Stem (ES) Cell Culture: Rl cells (a kind gift of Dr. S. McMahon, Thomas Jefferson University, Philadelphia, PA), are mouse embryonic stem cells and were cultured on tissue culture plates (BD Falcon, Franklin Lakes, NJ) coated with 0.1% (v/v) porcine gelatin (Sigma- Aldrich Corp, St. Louis, MO) in Dulbecco's modified Eagle's medium (DMEM; Invitrogen, Grand Island NY) in the presence of 1 % fetal bovine serum (ES-tested Hyclone, Perbio, Logan, UT) 0.1 mM 2-mercaptoethanol, 0.1 mM non-essential aminoacids, 2 mM Glutamine, 0. ImM sodium pyruvate, 10 mM HEPES, and 1000 unit/ml murine LIF (Chemicon International Inc., Tamecula, CA) 100 units/ml penicillin and 100 μ/ml streptomycin. Cells were trypsinized and re-plated every 2nd day and re-fed daily. In some experiments 5 mM or 10 mM of (R)-(-)-l, 3-Butanediol; (R)-(-)-3-Hydroxybutyric acid; Sodium L-lactate (Sigma-Aldrich Inc., St. Louis, MO) was added to the medium. In all the experiments, medium was replaced daily. Alkaline phosphatase (AP) staining was performed using Fast Red TR salt™ (Sigma) reagent, according to the manufacturer's protocol. Computer- assisted image analysis of alkaline phosphatase positive colonies was performed using an Olympus BX51 System Microscope (Olympus Corp., Miami, FL, USA) equipped with a Micropublisher 5.0 cooled CCD camera (Qlmaging Corp., BC). ImageJ software was used to

DB 1/ 69437516.1 analyze colonies size. MEFs were inactivated to be used as a feeder layer for mouse ES cells. Mitotic inactivation was performed by mitomycin C treatment. Briefly, fibroblasts were grown to 90% confluence and mitomycin was added to the growth medium at final concentration of 10pg/ml. Cells were treated for 3h. MEFs were trypsinized, counted, and frozen at the concentration of 3 x 10⁶/ml. 1ml of frozen feeders was used to coat a 24 well plate. All the ES cell experiments were performed at least 3 times in duplicate. Results were analyzed for statistical significance by the two tail Student's t-test.

[0177] Figures and Tables:

[0178] Reference is now made to Figure 1, which depicts HeatMaps for the intersection between MCF7 lactate-induced genes and transcripts that are highly expressed in neural stem cells. Note that these two gene sets have 461 intersecting genes in common. See Supplemental Table 4 for a detailed list. Overlapping genes are shown in panels A and B.

[0179] Reference is now made to Figure 2, which depicts HeatMaps for the intersection between MCF7 ketone-induced genes and transcripts that are highly expressed in hematopoietic stem cells. Note that these two gene sets have 31 1 intersecting genes in common. See

Supplemental Table 5 for a detailed list.

[0180] Reference is now made to Figure 3, which illustrates Venn diagrams for the transcriptional overlap between the lactate-induced and ketone-induced transcriptional profiles in MCF7 cells. Transcriptional overlap between the lactate- and ketone-induced gene profiles is shown. Using this approach, -1,433 overlapping genes were identified; 2,698 genes were found to be lactate-specific, while 2,708 genes were found to be ketone-specific. Gene set enrichment analysis (GSEA) revealed that all three gene sets (common, lactate-specific, and ketone-specific) remained associated with sternness, although differences were noted. The lactate-specific gene profile was most similar to neural stem cells, while the ketone-specific gene profile was most similar to hematopoietic stem cells. The genes commonly upregulated by both lactate and ketones were most similar to embryonic stem cells. Finally, the lactate-specific gene profile also showed significant overlap with two clinical gene signatures that predict poor outcome in liver cancer and multiple myeloma. Associations with ER(+) and ER(-) breast cancers were also noted. See Supplemental Table 3. [0181] Reference is now made to Figure 4, which depicts HeatMaps for the intersection between MCF7 lactate-specific genes and transcripts that are highly expressed in poor prognosis cancers. The lactate-specific gene profile showed significant overlap with two clinical gene

DB l/ 69437516.1 signatures that predict poor outcome in and multiple myeloma (MM, 37 genes overlap) and liver cancer (HCC, 31 genes overlap). See Supplemental Tables 6 and 7 for the detailed lists.

[0182] Reference is now made to Figure 5, which illustrates the lactate-induced gene signature is associated with ER(+) breast cancer and predicts poor clinical outcome. Figure 5A depicts Boxplots, which illustrate differential regulation of the lactate signature expression in breast cancer versus healthy breast tissue. Arrows indicate the directionality of differential regulation within each population. Figure 5B depicts Survival curves within low and high lactate signature-expressing populations, shown for overall survival in ER-positive breast cancer. This signature contains - 4,131 genes (See Supplemental Table 1). [0183] Reference is now made to Figure 6, which depicts the ketone-induced gene signature is associated with ER(+) breast cancer and predicts poor clinical outcome. Figure 6A shows Boxplots, which illustrate differential regulation of the ketone signature expression in breast cancer versus healthy breast tissue. Arrows indicate the directionality of differential regulation within each population. Figure 6B depicts Survival curves within low and high ketone signature-expressing populations, shown for overall survival in ER-positive breast cancer. This signature contains - 4,141 genes (See Supplemental Table 2).

[0184] Reference is now made to Figure 7, which shows that the lactate-induced gene signature predicts recurrence, metastasis, and decreased overall survival in luminal a breast cancers. Survival curves within low and high lactate signature-expressing populations are shown within the luminal A subtype for metastasis-free survival (Figure 7A), relapse-free survival (Figure 7B), and overall survival (Figure 7C). This signature contains - 4,131 genes (See

Supplemental Table 1). In panel C, it is important to note that overall survival data were available for a smaller number of luminal A breast cancer cases.

[0185] Reference is now made to Figure 8, which shows that the ketone-induced gene signature predicts recurrence, metastasis, and decreased overall survival in luminal a breast cancers. Survival curves within low and high ketone signature-expressing populations are shown within the luminal A subtype for metastasis-free survival (Figure 8A), relapse-free survival (Figure 8B), and overall survival (Figure 8C). This signature contains - 4,141 genes (See

Supplemental Table 2). In panel C, it is important to note that overall survival data were available for a smaller number of luminal A breast cancer cases.

[0186] Reference is now made to Figure 9, which shows that the ketone- and lactate-induced "stem cell" signatures predict decreased overall survival in luminal a breast cancers. Survival

DBl/ 69437516.1 curves within low and high stem-cell specific ketone signature-expressing populations are shown for overall survival within ER-positive disease (Figure 9A), and the luminal A subtype (Figure 9B). Similar results are shown for the stem-cell specific lactate signature in panel C (Figure 9C), with reductions in overall survival. These two signatures each contain -300-400 gene transcripts, see Supplemental Tables 4 and 5. In panel C, it is important to note that overall survival data were available for a smaller number of luminal A breast cancer cases.

[0187] Reference is now made to Figure 10, which shows that survival analysis for the intersection between MCF7 lactate-specific genes and transcripts that are highly expressed in poor prognosis cancers. Figure 10A illustrates Survival curves based on the intersection of the lactate and the HCC-derived signatures are shown within the luminal A subtype for overall survival. Figure 10B illustrates Survival curves based on the intersection of the lactate and the MM-derived signatures are shown for overall survival. These two signatures each contain -30- 40 gene transcripts, see Supplemental Tables 4 and 5. HCC, hepatocellular carcinoma; MM, multiple myeloma. [0188] Reference is now made to Figure 11, which shows that lactate and ketones increase histone acetylation in MCF7 cancer cells. MCF7 cells were treated with ketones and lactate. Then, we used acetylation-specific antibody probes to assess that status of histone acetylation. Note that both ketones and lactate increased histone acetylation. However, lactate had a more positive effect than ketones, and both resulted in a "laddering" effect, which most likely represents hyper-acetylation plus other protein modifications, such as phosphorylation, which affects the mobility of proteins in SDS-PAGE gels. As such, the lactate- and ketone-induced increases in histone acetylation may contribute to changes in genome-wide transcriptional profiling. For histone H4, two panels are shown. One panel shows the higher molecular weight "laddering" species; the other panel shows a single band, which most likely represents the mono- acetylated species of histone H4, (3HB, 3-hydroxy-butryate; L-Lac, L-Lactate).

[0189] Reference is now made to Figure 12, which shows that ketones and lactate promote the growth of mouse embryonic stem (ES) cells in culture. In Figure 12A, Rl murine ES cells were grown in the absence or presence of various metabolites, then colony size and number were quantitated. In Figure 12B, representative images of ES cell colonies are shown. Note that both colony size and number were significantly increased (p < 0.01). Importantly, colony number increased up to 3-fold. BD, butanediol; 3HB, 3-hydroxy-butryate; L-Lac, L-Lactate.

[0190] Figure 13 illustratesa new metabolic strategy for personalized cancer diagnosis and therapy. Outlined is a general experimental strategy for personalized cancer medicine. Briefly,

DB 1/ 69437516.1 cancer cells of a particular tumor type are selected for study. Then, these cancer cells are cultured in the absence and presence of high-energy metabolites, such as ketones and/or lactate. This should allow the investigator to generate a new gene signature based on transcriptional profiling (exon-array). This signature could then be used to select the patients that are undergoing this type of tumor metabolism, and correlate tumor metabolism with clinical outcome, such as recurrence and metastasis. High-risk patients could then be identified at diagnosis and treated with new therapies that are designed to target oxidative mitochondrial metabolism, such as metformin which is a specific inhibitor of mitochondrial complex I.

[0191] Though not wishing to be bound by theory, Figure 14 illustrates possible mechanism(s) of action of ketones and lactate, converging on Acetyl-CoA. Lactate and Ketones are converted to Acetyl-CoA, which can then be used via oxidative mitochondrial metabolism to generate high amounts of ATP. Alternatively, Acetyl-CoA could also be utilized for the acetylation of proteins, such as histones. Histone acetylation has been associated with increases in gene expression. References:

1. Pavlides S, Whitaker-Menezes D, Castello-Cros R, Flomenberg N, Witkiewicz AK, Frank PG, Casimiro MC, Wang C, Fortina P, Addya S, Pestell RG, Martinez-Outschoorn UE, Sotgia F, Lisanti MP. The reverse Warburg effect: Aerobic glycolysis in cancer associated fibroblasts and the tumor stroma. Cell Cycle 2009; 8:3984-4001.

2. Pavlides S, Tsirigos A, Migneco G, Whitaker-Menezes D, Chiavarina B, Flomenberg N, Frank PG, Casimiro MC, Wang C, Pestell RG, Martinez-Outschoorn UE, Howell A, Sotgia F, Lisanti MP. The Autophagic Tumor Stroma Model of Cancer: Role of Oxidative Stress and Ketone Production in Fueling Tumor Cell Metabolism. Cell Cycle 2010; 9:3485-505.

3. Pavlides S, Tsirigos A, Vera I, Flomenberg N, Frank PG, Casimiro MC, Wang C, Fortina P, Addya S, Pestell RG, Rigoutsos I, Martinez-Outschoorn UE, Sotgia F, Lisanti MP. Loss of

Stromal Caveolin-1 Leads to Oxidative Stress, Mimics Hypoxia, and Drives Inflammation in the Tumor Microenvironment, Conferring the "Reverse Warburg Effect": A Transcriptional Informatics Analysis with Validation. Cell Cycle 2010; 9:2201-19.

4. Martinez-Outschoorn UE, Balliet RM, Rivadeneira DB, Chiavarina B, Pavlides S, Wang C, Whitaker-Menezes D, Daumer KM, Lin Z, Witkiewicz AK, Flomenberg N, Howell A, Pestell

RG, Knudsen ES, Sotgia F, Lisanti MP. Oxidative Stress in Cancer Associated Fibroblasts Drives Tumor-Stroma Co-Evolution: A New Paradigm for Understanding Tumor Metabolism, the Field Effect, and Genomic Instability in Cancer Cells. Cell Cycle 2010; 9:3256-76.

5. Martinez-Outschoorn UE, Pavlides S, Whitaker-Menezes D, Daumer KM, Milliman J , Chiavarina B, Migneco G, Witkiewicz AK, Martinez-Cantarin MP, Flomenberg N, Howell A,

Pestell RG, Lisanti MP, Sotgia F. Tumor Cells Induce the Cancer Associated Fibroblast Phenotype Via Caveolin-1 Degradation: Implications for Breast Cancer and DCIS Therapy with Autophagy Inhibitors. Cell Cycle 2010; 9:2423-33.

DBl/ 69437516.1 6. Martinez-Outschoorn UE, Trimmer C, Lin Z, Whitaker-Menezes D, Chiavarina B, Zhou J, Wang C, Pavlides S, Martinez-Cantarin MP, Capozza F, Witkiewicz AK, Flomenberg N, Howell A, Pestell RG, Caro J, Lisanti MP, Sotgia F. Autophagy in Cancer Associated Fibroblasts Promotes Tumor Cell Survival: Role of Hypoxia, HIF1 Induction, and NFKB Activation in the Tumor Stromal Microenvironment. Cell Cycle 2010; 9:3515-33.

7. Martinez-Outschoorn UE, Whitaker-Menezes D, Pavlides S, Chiavarina B, Bonuccelli G, Casey T, Tsirigos A, Migneco G, Witkiewicz A, Balliet R, Mercier I, Wang C, Flomenberg N, Howell A, Lin Z, Caro J, Pestell RG, Sotgia F, Lisanti MP. The Autophagic Tumor Stroma Model of Cancer or "Battery-Operated Tumor Growth": A Simple Solution to the Autophagy Paradox. Cell Cycle 2010; 9:In Press.

8. Bonuccelli G, Tsirigos A, Whitaker-Menezes D, Pavlides S, Pestell RG, Chiavarina B, Frank PG, Flomenberg N, Howell A, Martinez-Outschoorn UE, Sotgia F, Lisanti MP. Ketones and Lactate "Fuel" Tumor Growth and Metastasis: Evidence that Epithelial Cancer Cells Use Oxidative Mitochondrial Metabolism. Cell Cycle 2010; 9:3506-14.

9. Lisanti MP, Martinez-Outschoorn UE, Chiavarina B, Pavlides S, Whitaker-Menezes D, Tsirigos A, Witkiewicz A, Lin Z, Balliet R, Howell A, Sotgia F. Understanding the "lethal" drivers of tumor-stroma co-evolution: Emerging role(s) for hypoxia, oxidative stress and autophagy/mitophagy in the tumor micro-environment. Cancer Biol Ther 2010; 10:537-42.

10. Martinez-Outschoorn UE, Pavlides S, Howell A, Pestell RG, Tanowitz HB, Sotgia F, Lisanti MP. Stromal-Epithelial Metabolic Coupling in Cancer: Integrating Autophagy and

Metabolism in the Tumor Microenvironment. Int J Biochem Cell Biol 201 1; In Press.

11. Gorr TA, Wichmann D, Pilarsky C, Theurillat JP, Fabrizius A, Laufs T, Bauer T, Koslowski M, Horn S, Burmester T, Hankeln T, Kristiansen G. Old proteins - new locations: myoglobin, haemoglobin, neuroglobin and cytoglobin in solid tumours and cancer cells. Acta Physiol (Oxf) 2011 ; In Press.

12. Kristiansen G, Rose M, Geisler C, Fritzsche FR, Gerhardt J, Luke C, Ladhoff AM, Knuchel R, Dietel M, Moch H, Varga Z, Theurillat JP, Gorr TA, Dahl E. Endogenous myoglobin in human breast cancer is a hallmark of luminal cancer phenotype. Br J Cancer 2010; 102:1736- 45.

13. Moreaux J, Cremer FW, Reme T, Raab M, Mahtouk K, Kaukel P, Pantesco V, De Vos J, Jourdan E, Jauch A, Legouffe E, Moos M, Fiol G, Goldschmidt H, Rossi JF, Hose D, Klein B. The level of TACI gene expression in myeloma cells is associated with a signature of microenvironment dependence versus a plasmablastic signature. Blood 2005; 106:1021-30.

14. Brizel DM, Schroeder T, Scher RL, Walenta S, Clough RW, Dewhirst MW, Mueller- Klieser W. Elevated tumor lactate concentrations predict for an increased risk of metastases in head-and-neck cancer. Int J Radiat Oncol Biol Phys 2001; 51 :349-53.

15. Walenta S, Wetterling M, Lehrke M, Schwickert G, Sundfor K, Rofstad EK, Mueller- Klieser W. High lactate levels predict likelihood of metastases, tumor recurrence, and restricted patient survival in human cervical cancers. Cancer Res 2000; 60:916-21.

16. Walenta S, Mueller-Klieser WF. Lactate: mirror and motor of tumor malignancy. Semin Radiat Oncol 2004; 14:267-74.

DB U 69437516.1 17. Walenta S, Salameh A, Lyng H, Evensen JF, Mitze M, Rofstad EK, Mueller-Klieser W. Correlation of high lactate levels in head and neck tumors with incidence of metastasis. Am J Pathol 1997; 150:409-15.

18. Sculier JP, Nicaise C, Klastersky J. Lactic acidosis: a metabolic complication of extensive metastatic cancer. Eur J Cancer Clin Oncol 1983; 19:597-601.

19. Varanasi UR, Carr B, Simpson DP. Lactic acidosis associated with metastatic breast carcinoma. Cancer Treat Rep 1980; 64:1283-5.

20. McConnell AA, Parfitt VL, Walker PR. An unusual case of shock in a young woman. Postgrad Med J 1989; 65: 120.

21. Warner E. Type B lactic acidosis and metastatic breast cancer. Breast Cancer Res Treat 1992; 24:75-9.

22. Evans TR, Stein RC, Ford HT, Gazet JC, Chamberlain GV, Coombes RC. Lactic acidosis. A presentation of metastatic breast cancer arising in pregnancy. Cancer 1992; 69:453-6.

23. Cheng JC, Esparza SD, Knez VM, Sakamoto KM, Moore TB. Severe lactic acidosis in a 14-year-old female with metastatic undifferentiated carcinoma of unknown primary. J Pediatr

Hematol Oncol 2004; 26:780-2.

24. Xu HN, Nioka S, Glickson JD, Chance B, Li LZ. Quantitative mitochondrial redox imaging of breast cancer metastatic potential. J Biomed Opt 2010; 15:036010.

25. Chen V, Shtivelman E. CC3/TIP30 regulates metabolic adaptation of tumor cells to glucose limitation. Cell Cycle 2010; 9:4941-53.

26. Chen EI, Hewel J, Krueger JS, Tiraby C, Weber MR, Kralli A, Becker K, Yates JR, 3rd, Felding-Habermann B. Adaptation of energy metabolism in breast cancer brain metastases. Cancer Res 2007; 67:1472-86.

27. Magistretti PJ. Neuron-glia metabolic coupling and plasticity. J Exp Biol 2006; 209:2304- 11.

28. Magistretti PJ. Role of glutamate in neuron-glia metabolic coupling. Am J Clin Nutr 2009; 90-.875S-80S.

29. Magistretti PJ, Pellerin L. The contribution of astrocytes to the 18F-2-deoxyglucose signal in PET activation studies. Mol Psychiatry 1996; 1 :445-52.

30. Pavlides S, Tsirigos A, Vera I, Flomenberg N, Frank PG, Casimiro MC, Wang C, Pestell RG, Martinez-Outschoorn UE, Howell A, Sotgia F, Lisanti MP. Transcriptional evidence for the "Reverse Warburg Effect" in human breast cancer tumor stroma and metastasis: similarities with oxidative stress, inflammation, Alzheimer's disease, and "Neuron-Glia Metabolic Coupling". Aging (Albany NY) 2010; 2: 185-99.

31. Wohnsland S, Burgers HF, Kuschinsky W, Maurer MH. Neurons and neuronal stem cells survive in glucose-free lactate and in high glucose cell culture medium during normoxia and anoxia. Neurochem Res 2010; 35: 1635-42.

32. Birket MJ, Orr AL, Gerencser AA, Madden DT, Vitelli C, Swistowski A, Brand MD, Zeng X. A reduction in ATP demand and mitochondrial activity with neural differentiation of human embryonic stem cells. J Cell Sci 2010; 124:348-58.

DB l/ 69437516.1 33. Harvey A, Gibson T, Lonergan T, Brenner C. Dynamic regulation of mitochondrial function in preimplantation embryos and embryonic stem cells. Mitochondrion 2011 ; In Press.

34. Markowetz F, Mulder KW, Airoldi EM, Lemischka I , Troyanskaya OG. Mapping dynamic histone acetylation patterns to gene expression in nanog-depleted murine embryonic stem cells. PLoS Comput Biol 2010; 6:el001034.

35. Fenselau A, Wallis K, Morris HP. Subcellular localization of acetoacetate coenzyme A transferase in rat hepatomas. Cancer Res 1976; 36:4429-33.

36. Kallinowskil F, Davel S, Vaupell P, Baessler KH, Wagner K. Glucose, lactate, and ketone body utilization by human mammary carcinomas in vivo. Adv Exp Med Biol 1985; 191:763-73. 37. Authier S, Tremblay S, Dumulon V, Dubuc C, Ouellet R, Lecomte R, Cunnane SC, Benard F. [11C] acetoacetate utilization by breast and prostate tumors: a PET and biodistribution study in mice. Mol Imaging Biol 2008; 10:217-23.

38. Prenen GH, Go KG, Zuiderveen F, Paans AM, Vaalburg W. An improved synthesis of carbon- 1 1 labeled acetoacetic acid and an evaluation of its potential for the investigation of cerebral pathology by positron emission tomography. Int J Rad Appl Instrum A 1990; 41 : 1209- 16.

39. Dykens JA, Jamieson J, Marroquin L, Nadanaciva S, Billis PA, Will Y. Biguanide- induced mitochondrial dysfunction yields increased lactate production and cytotoxicity of aerobically-poised HepG2 cells and human hepatocytes in vitro. Toxicol Appl Pharmacol 2008; 233:203-10.

40. Pollak M. Metformin and other biguanides in oncology: advancing the research agenda. Cancer Prev Res (Phila) 2010; 3:1060-5.

41. Memmott RM, Mercado JR, Maier CR, Kawabata S, Fox SD, Dennis PA. Metformin prevents tobacco carcinogen-induced lung tumorigenesis. Cancer Prev Res (Phila) 2010; 3:1066-76.

42. Hirsch HA, Iliopoulos D, Tsichlis PN, Struhl K. Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission. Cancer Res 2009; 69:7507-11.

43. Vazquez- Martin A, Oliveras-Ferraros C, Barco SD, Martin-Castillo B, Menendez JA. The anti-diabetic drug metformin suppresses self-renewal and proliferation of trastuzumab-resistant tumor-initiating breast cancer stem cells. Breast Cancer Res Treat 2010; In Press.

44. Vazquez-Martin A, Oliveras-Ferraros C, Cufi S, Martin-Castillo B, Menendez JA. Metformin and energy metabolism in breast cancer: from insulin physiology to tumour-initiating stem cells. Curr Mol Med 2010; 10:674-91.

45. Vazquez-Martin A, Oliveras-Ferraros C, Cufi S, Del Barco S, Martin-Castillo B, Menendez JA. Metformin regulates breast cancer stem cell ontogeny by transcriptional regulation of the epithelial-mesenchymal transition (EMT) status. Cell Cycle 2010; 9:3807-14.

46. Biradar V, Moran JL, Peake SL, Peter JV. Metformin-associated lactic acidosis (MALA): clinical profile and outcomes in patients admitted to the intensive care unit. Crit Care Resusc 2010; 12:191-5.

DB 1/ 69437516.1 47. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, Mesirov JP. Gene set enrichment analysis: a knowledge- based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A 2005; 102:15545-50.

48. Barrett T, Troup DB, Wilhite SE, Ledoux P, Rudnev D, Evangelista C, Kim IF, Soboleva A, Tomashevsky M, Edgar R. NCBI GEO: mining tens of millions of expression profiles- database and tools update. Nucl Acids Res 2007; 35:D760-5.

49. Brazma A, Parkinson H, Sarkans U, Shojatalab M, Vilo J, Abeygunawardena N, Holloway E, Kapushesky M, Kemmeren P, Lara GG, Oezcimen A, Rocca-Serra P, Sansone SA. ArrayExpress— a public repository for microarray gene expression data at the EBI. Nucleic Acids Res 2003; 31 :68-71.

50. Ertel A. Bimodal gene expression and biomarker discovery. Cancer Inform 2010; 9:11-4.

51. Ertel A, Dean JL, Rui H, Liu C, Witkiewicz AK, Knudsen KE, Knudsen ES. RB-pathway disruption in breast cancer: differential association with disease subtypes, disease-specific prognosis and therapeutic response. Cell Cycle 2010; 9: 153-63.

52. Hu Z, Fan C, Oh DS, Marron JS, He X, Qaqish BF, Livasy C, Carey LA, Reynolds E, Dressier L, Nobel A, Parker J, Ewend MG, Sawyer LR, Wu J, Liu Y, Nanda R, Tretiakova M, Ruiz Orrico A, Dreher D, Palazzo JP, Perreard L, Nelson E, Mone M, Hansen H, Mullins M, Quackenbush JF, Ellis MJ, Olopade OI, Bernard PS, Perou CM. The molecular portraits of breast tumors are conserved across microarray platforms. BMC Genomics 2006; 7:96.

Tables:

Table 1. Cellular Processes Increased in MCF7 Cells Treated with Lactate

Data Set P-value Detailed Description

Stem Cells

STEMCELL NEURAL UP 8.45E-23 Enriched in mouse neural stem cells,

compared to differentiated brain and bone marrow cells

STEMCELL EMBRYONIC UP 9.31E-17 Enriched in mouse embryonic stem cells, compared to differentiated brain and bone marrow cells

STEMCELL HEMATOPOIETIC Enriched in mouse hematopoietic stem UP cells, compared to differentiated brain and bone marrow cells

STEMCELL COMMON UP 9.95E-05 Enriched in mouse embryonic, neural and hematopoietic stem cells, compared to differentiated brain and bone marrow cells

HSC LTHSC ADULT 1.94E-04 Up-regulated in mouse long-term functional hematopoietic stem cells from adult bone marrow (LT-HSC Shared + Adult)

HSC LTHSC FETAL 4.79E-04 Up-regulated in mouse long-term functional hematopoietic stem cells from fetal liver (LT-HSC Shared)

HSC LTHSC SHARED 4.79E-04 Up-regulated in mouse long-term functional hematopoietic stem cells from both adult bone marrow and fetal liver (Cluster i, LTHSC Shared)

DB l/ 69437516.1 Table 1. Cellular Processes Increased in MCF7 Cells Treated with Lactate Data Set P-value Detailed Description

HADDAD HSC CD 10 UP 1.46E-03 Genes upregulated in human hematopoietic stem cells of the line CD45RA(hi) Lin- CD 10+, which are biased toward developing into B cells, versus

CD45RA(int) CD7- and CD45RA(hi) CD7+.

DNA Damage Response

UVC XPCS ALL DN 4.57E-23 Down-regulated at any timepoint following treatment of XPB/CS fibroblasts with 3 J/m^A2 UVC

UVC XPCS 8HR DN 7.07E-21 Down-regulated at 8 hours following

treatment of XPB/CS fibroblasts with 3 J/m^A2 UVC

UVC TTD ALL DN 9.84E-18 Down-regulated at any timepoint following treatment of XPB/TTD fibroblasts with 3 J/m^A2 UVC

UVC TTD 4HR DN 5.80E-15 Down-regulated at 4 hours following

treatment of XPB/TTD fibroblasts with 3 J/m^A2 UVC

UVC XPCS 4HR DN 8.87E-11 Down-regulated at 4 hours following

treatment of XPB/CS fibroblasts with 3 J/m^A2 UVC

DNA Damage Response

UVC TTD-XPCS COMMON DN Down-regulated at any timepoint following treatment of both XPB/CS and XPB/TTD fibroblasts with 3 J/m^A2 UVC

UVB NHEK1 DN 2.47E-09 Downregulated by UV-B light in normal human epidermal keratinocytes

UVC TTD 8HR DN 1.33E-08 Down-regulated at 8 hours following

treatment of XPB/TTD fibroblasts with 3 J/m^A2 UVC

Breast Cancer

BRCA ER NEG 8.50E-06 Genes whose expression is consistently negatively correlated with estrogen receptor status in breast cancer - higher expression is associated with ER-negative tumors

Transcription Factors and Signaling Molecules Associated with Proliferation, Sternness, and Cell Migration

GGGCGGR__V$SP1_Q6 8.22E-11 Genes with promoter regions [-2kb,2kb] around transcription start site containing the motif GGGCGGR which matches annotation for SP1: Spl transcription factor

GGGAGGRR_V$MAZ_Q6 2.68E-08 Genes with promoter regions [-2kb,2kb] around transcription start site containing the motif GGGAGGRR which matches annotation for MAZ: MYC-associated zinc finger protein (purine-binding transcription factor)

TTGTTT V$FOX04 01 3.17E-08 Genes with promoter regions [-2kb,2kb] around transcription start site containing the motif TTGTTT which matches annotation

DB1/ 69437₅16.1 Table 1. Cellular Processes Increased in MCF7 Cells Treated with Lactate

Data Set P-value Detailed Description

for MLLT7: myeloid/lymphoid or mixed- lineage leukemia (trithorax homolog, Drosophila); translocated to, 7

CTTTGT_V$LEF1_Q2 7.86E-08 Genes with promoter regions [-2kb,2kb] around transcription start site containing the motif CTTTGT which matches annotation for LEF1: lymphoid enhancer-binding factor 1

Transcription Factors and Signaling Molecules Associated with Proliferation, Sternness, and Cell Migration

CAGGTG_V$E12_Q6 Genes with promoter regions [-2kb,2kb] around transcription start site containing the motif CAGGTG which matches annotation for TCF3: transcription factor 3 (E2A immunoglobulin enhancer binding factors E12/E47)

SCGGAAGY V$ELK1 02 Genes with promoter regions [-2kb,2kb] around transcription start site containing the motif SCGGAAGY which matches annotation for ELK1: ELK1, member of ETS oncogene family

GCM MAP4K4 139 Neighborhood of MAP4K4 mitogen- activated protein kinase kinase kinase kinase 4 in the GCM expression compendium

HS A0451 O FOCAL ADHESION 1.55E-05 Genes involved in focal adhesion

GCM ERBB2IP 53 2.54E-05 Neighborhood of ERBB2IP erbb2

interacting protein in the GCM expression compendium

BRENT ANI SIGNALING Cancer related genes involved in the cell signaling

Table 2. Cellular Processes Increased in MCF7 Cells Treated with Ketones.

Data Set P-value Detailed Description

Stem Cells

STEMCELL HEMATOPOIETIC 2.88E-09 Enriched in mouse hematopoietic stem UP cells, compared to differentiated brain and bone marrow cells

STEMCELL EMBRYONIC UP 6.29E-04 Enriched in mouse embryonic stem cells, compared to differentiated brain and bone marrow cells

STEMCELL NEURAL UP 6.74E-04 Enriched in mouse neural stem cells,

compared to differentiated brain and bone marrow cells

DNA Damage Response

UVC XPCS ALL DN 2.75E-13 Down-regulated at any timepoint following treatment of XPB/CS fibroblasts with 3 J/m^A2 UVC

UVC XPCS 8HR DN 1.39E-12 Down-regulated at 8 hours following

treatment of XPB/CS fibroblasts with 3

DBl/ 69437516.1 Table 2. Cellular Processes Increased in MCF7 Cells Treated with Ketones.

Data Set P-value Detailed Description

J/m^A2 UVC

UVC_XPCS_4HR_DN 5.34E-07 Down-regulated at 4 hours following

treatment of XPB/CS fibroblasts with 3 J/m^A2 UVC

UVC TTD ALL DN 6.87E-07 Down-regulated at any timepoint following treatment of XPB/TTD fibroblasts with 3 J/m^A2 UVC

UVC TTD 4HR DN 6.16E-06 Down-regulated at 4 hours following

treatment of XPB/TTD fibroblasts with 3 J/m^A2 UVC

UVC_TTD_8HR_DN 2.07E-05 Down-regulated at 8 hours following

treatment of XPB/TTD fibroblasts with 3 J/m^A2 UVC

U VB_NHEK 1 _DN 2.45E-05 Downregulated by UV-B light in normal human epidermal keratinocytes

UVB_NHE 3_C8 8.75E-05 Regulated by UV-B light in normal human epidermal keratinocytes, cluster 8

UVC LOW ALL DN 9.29E-05 Down-regulated at any timepoint following treatment of WS1 human skin fibroblasts with UVC at a low dose (10 J/m^A2) (clusters cl-c5)

Breast Cancer

BRCA ER POS 1.15E-04 Genes whose expression is consistently positively correlated with estrogen receptor status in breast cancer - higher expression is associated with ER-positive tumors

Transcription Factors and Signaling Associated with Proliferation, Sternness, and

Migration

GGGCGGR_V$SP1_Q6 1.00E-13 Genes with promoter regions [-2kb,2kb] around transcription start site containing the motif GGGCGGR which matches annotation for SP1: Spl transcription factor

CAGGTG_V$E12_Q6 7.79E-11 Genes with promoter regions [-2kb,2kb] around transcription start site containing the motif CAGGTG which matches annotation for TCF3: transcription factor 3 (E2A immunoglobulin enhancer binding factors E12/E47)

TTGTTT V$FOX04 01 2.37E-08 Genes with promoter regions [-2kb,2kb] around transcription start site containing the motif TTGTTT which matches annotation for MLLT7: myeloid/lymphoid or mixed- lineage leukemia (trithorax homolog, Drosophila); translocated to, 7

HS A04510 FOCAL ADHESION 3.76E-07 Genes involved in focal adhesion

TGACAGNY VSMEISl 01 2.21E-06 Genes with promoter regions [-2kb,2kb] around transcription start site containing the motif TGACAGNY which matches annotation for MEIS1: Meisl, myeloid ecotropic viral integration site 1 homolog (mouse)

DBl/ 69437516.1 Table 2. Cellular Processes Increased in MCF7 Cells Treated with Ketones.

Data Set P-value Detailed Description

GGGAGGRR_V$MAZ_Q6 3.65E-06 Genes with promoter regions [-2kb,2kb] around transcription start site containing the motif GGGAGGRR which matches annotation for MAZ: MYC-associated zinc finger protein (purine-binding transcription factor)

CTTTGT_V$LEF 1_Q2 4.63E-06 Genes with promoter regions [-2kb,2kb] around transcription start site containing the motif CTTTGT which matches annotation for LEF1: lymphoid enhancer-binding factor 1

Transcription Factors and Signaling Associated with Proliferation, Stemness, and

Migration

TC ANNTGA Y VSSREBP 1 01 1.09E-05 Genes with promoter regions [-2kb,2kb] around transcription start site containing the motif TCANNTGAY

which matches annotation for SREBF1: sterol regulatory element binding transcription factor 1

GGGTGGRR V$PAX4 03 1.38E-05 Genes with promoter regions [-2kb,2kb] around transcription start site containing the motif GGGTGGRR which matches annotation for PAX4: paired box gene 4

TGACCTY_V$ERR1_Q2 1.59E-05 Genes with promoter regions [-2kb,2kb] around transcription start site containing the motif TGACCTY which matches annotation for ESRRA: estrogen-related receptor alpha

HSA04512__ECM_RECEPTOR JN 1.08E-04 Genes involved in ECM-receptor

TERACTION interaction

BRENTANI SIGNALING 1.06E-04 Cancer related genes involved in the cell signaling

CELL ADHESION 3.70E-04 The attachment of a cell, either to another cell or to the extracellular matrix, via cell adhesion molecules.

HS A04012_ERBB_SIGNALING_P Genes involved in ErbB signaling pathway ATHWAY

Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P ^ Change value

ankyrin repeat and sterile alpha motif domain

ANKS1A containing 1A 13.893079 0.00129568 ubiquitin-conjugating enzyme E2D 2

UBE2D2 (UBC4/5 homolog, yeast) 11.637619 0.00544828

MGAT5 mannosyl (alpha- 1 ,6-)-glycoprotein beta- 1 ,6- 9.050858 0.00126631

DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P

Change value

N-acetyl-glucosaminyltransferase

SRP19 signal recognition particle 19kDa 8.965928 0.00278124

EIF5B eukaryotic translation initiation factor 5B 8.853053 0.04053256

RAD50 RAD50 homolog (S. cerevisiae) 7.941115 0.00729083

FDX1L N/A 7.063176 0.00184751

CHMP2B chromatin modifying protein 2B 6.857511 0.03281982 calmodulin regulated spectrin-associated

CAMSAP1L1 protein 1 -like 1 6.801826 0.00745505

RNASEN ribonuclease type III, nuclear 6.195086 0.00604981

PRDX1 peroxiredoxin 1 6.15612 0.02465945

PHF3 PHD finger protein 3 6.115121 0.01437164

GCC2 GRIP and coiled-coil domain containing 2 6.081664 0.01032446 glycine cleavage system protein H

GCSH (aminomethyl carrier) 6.024608 0.04401522

ZNF721 zinc finger protein 721 5.910076 0.01377737

Rho-associated, coiled-coil containing protein

ROCK2 kinase 2 5.852909 0.03308627

BCLAF1 BCL2-associated transcription factor 1 5.819574 0.00240797

PCM1 pericentriolar material 1 5.734292 0.03714159 ubiquitin-conjugating enzyme E2D 3

UBE2D3 (UBC4/5 homolog, yeast) 5.713108 0.021 14428

CD55 molecule, decay accelerating factor for

CD55 complement (Cromer blood group) 5.683509 0.00441274

COBLL1 COBL-like 1 5.653954 0.00632952

CCNG1 cyclin Gl 5.586583 0.01011364

GOLGA4 golgin A4 5.560977 0.02300835

PRP38 pre-mRNA processing factor 38

PRPF38B (yeast) domain containing B 5.538255 0.01964032

DSP desmoplakin 5.501278 0.03396202

AKAP9 A kinase (PRKA) anchor protein (yotiao) 9 5.490807 0.00483518 heterogeneous nuclear ribonucleoprotein HI

HNRNPH1 (H) 5.461596 0.00966327

YBX1 Y box binding protein 1 5.455093 0.00261863

NMD3 NMD3 homolog (S. cerevisiae) 5.436879 0.00447774

SLAIN2 SLAIN motif family, member 2 5.395218 0.02030348 general transcription factor IIIC, polypeptide

GTF3C2 2, beta HOkDa 5.378955 0.00634443

UBAP2L ubiquitin associated protein 2-like 5.315991 0.00823742

TET3 tet oncogene family member 3 5.263592 0.01968249

SEPT11 - N/A 5.242439 0.0186971

R3HDM1 R3H domain containing 1 5.22919 0.03721685

MTDH metadherin 5.228131 0.01520368

H3F3A H3 histone, family 3 A 5.188202 0.0162106

SPAST spastin 5.161775 6.01E-05

COL6A3 collagen, type VI, alpha 3 5.109395 0.02218458

PPIG peptidylprolyl isomerase G (cyclophilin G) 5.060878 0.04469338

ODC1 Ornithine decarboxylase 1 5.027819 0.01411638

LXN latexin 5.025051 0.00486952

RPS13 ribosomal protein S13 5.023618 0.01030916

KIAA1143 KIAA1143 5.017609 0.02515374 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

ATP-binding cassette, sub-family A (ABC1),

ABCA12 member 12 0.02867676 UBE2V1 ubiquitin-conjugating enzyme E2 variant 1 0.01282914 SNX2 sorting nexin 2 0.03586009 protein tyrosine phosphatase, non-receptor

PTPN12 type 12 4.969861 0.02927481

DEAD (Asp-Glu-Ala-Asp) box polypeptide

DDX46 46 0.03654288 NCL nucleolin 0.0056764 BZW2 basic leucine zipper and W2 domains 2 0.0016293 IGF2R insulin-like growth factor 2 receptor 0.02505894

SWI/SNF related, matrix associated, actin

dependent regulator of chromatin, subfamily

SMARCA5 a, member 5 0.0187601 sema domain, immunoglobulin domain (Ig),

SEMA3C short basic domain, secreted, (semaphorin) 3C 0.03498121 NOL8 nucleolar protein 8 0.02345704 eukaryotic translation elongation factor 1

EEF1AL7 alpha-like 7 0.00831902 SMC4 structural maintenance of chromosomes 4 0.03654239 MARCH 1 - N/A 0.01485637 PPIL4 peptidylprolyl isomerase (cyclophilin)-like 4 0.02987658 human immunodeficiency virus type I

HIVEP1 enhancer binding protein 1 0.01033624

RPS3A ribosomal protein S3A 0.03886604

TMF1 TATA element modulatory factor 1 0.00700515

FUCA2 fucosidase, alpha-L- 2, plasma 0.03214858

LRPPRC leucine-rich PPR-motif containing 0.04328232

MDN1 MDN1, midasin homolog (yeast) 0.02424848

CAPNS1 calpain, small subunit 1 0.02265225

ZBTB45 zinc finger and BTB domain containing 45 0.00535187

TROVE2 TROVE domain family, member 2 0.00092942

Smg-7 homolog, nonsense mediated mRNA

SMG7 decay factor (C. elegans) 4.490393 0.02508655

ASF1 anti-silencing function 1 homolog A (S.

ASF1A cerevisiae) 0.01353041

IV S1ABP influenza virus NS1A binding protein 0.04032226

NIPBL Nipped-B homolog (Drosophila) 0.02143111

Taxi (human T-cell leukemia virus type I)

TAX1BP1 binding protein 1 0.00321459 PNN pinin, desmosome associated protein 0.00780293 RAP1A RAP1A, member of RAS oncogene family 0.01890408 C7orf28A chromosome 7 open reading frame 28A 0.01053364 leucine rich repeat (in FLU) interacting

LRRFIP2 protein 2 0.03555186

TMEM183A transmembrane protein 183 A 0.03980656

WDR64 WD repeat domain 64 0.03698108 myeloid/lymphoid or mixed-lineage leukemia

MLL5 5 (trithorax homolog, Drosophila) 0.02455489 DNAJC21 DnaJ (Hsp40) homolog, subfamily C, member 0.04182551 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P

Change value

21

epidermal growth factor receptor pathway

EPS 15 substrate 15 4.323186 0.01089252 phosphoinositide-3-kinase, regulatory subunit

PIK3R3 3 (gamma) 4.285617 0.03338317

ENAH enabled homolog (Drosophila) 4.27782 0.01207197

ZMYM4 zinc finger, MYM-type 4 4.267182 0.01393137

STAG1 stromal antigen 1 4.216755 0.04048666 signal transducing adaptor molecule (SH3

STAM2 domain and IT AM motif) 2 4.170061 0.00948584

Ras association (RalGDS/AF-6) domain

RASSF5 family member 5 4.1482 0.0214628

RPL37 ribosomal protein L37 4.143363 0.00991689

ZFHX3 zinc finger homeobox 3 4.10981 1 0.00434282

METTL5 methyltransferase like 5 4.101808 0.01369737

TBPL1 TBP-like 1 4.09397 0.04649146

LAPTM4A lysosomal protein transmembrane 4 alpha 4.093129 0.00222108 translocated promoter region (to activated

TPR MET oncogene) 4.08363 0.00433995 biorientation of chromosomes in cell division

BOD1L l-like 4.074719 0.00585576

ADAR adenosine deaminase, RNA-specific 4.052521 0.01933813

CCNI cyclin I 4.045976 0.02394342

NUP210 nucleoporin 21 OkDa 4.045013 0.004972

MINA MYC induced nuclear antigen 4.035887 0.00750673

GOLGB1 golgin Bl 4.035684 0.03247406

BOLA2 bolA homolog 2 (E. coli) 4.020715 0.00624889 proteasome (prosome, macropain) 26S

PSMD1 subunit, non-ATPase, 1 4.011931 0.00720011 bone morphogenetic protein receptor, type II

BMPR2 (serine/threonine kinase) 4.0114 0.00367358

CEP350 centrosomal protein 35 OkDa 4.00531 0.01009971

ANXA4 annexin A4 3.996529 0.03274477 proteasome (prosome, macropain) 26S

PSMC2 subunit, ATPase, 2 3.987502 0.00426193

HIPK1 homeodomain interacting protein kinase 1 3.965913 0.03717961 leucine-rich repeats and calponin homology

LRCH3 (CH) domain containing 3 3.959914 0.03286447

DEAH (Asp-Glu-Ala-His) box polypeptide

DHX15 15 3.926349 0.04456131

WRN Werner syndrome, RecQ helicase-like 3.906743 0.00075415

S N stannin 3.894112 0.02352978 methylmalonic aciduria (cobalamin

MMADHC deficiency) cblD type, with homocystinuria 3.893559 0.03029769

ZNF141 zinc finger protein 141 3.893084 0.00202819

MATR3 matrin 3 3.887861 0.03276835

RWDD4A RWD domain containing 4A 3.882013 0.02249924

6-Mar N/A 3.872003 0.03676463

SEC24D SEC24 family, member D (S. cerevisiae) 3.863242 0.01372926

TNR tenascin R (restrictin, janusin) 3.854513 0.038419

DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

GTPase activating Rap/RanGAP domain-like

GARNL1 1 3.849157 0.00293828

DBF4 DBF4 homolog (S. cerevisiae) 3.845044 0.01450426

MOCS1 molybdenum cofactor synthesis 1 3.840436 0.03981892

ZC3H6 zinc finger CCCH-type containing 6 3.838372 0.01211492

HSPA1A heat shock 70kDa protein 1 A 3.815485 0.03448563

NARG1 NMDA receptor regulated 1 3.802809 0.03569002

NOP58 NOP58 ribonucleoprotein homolog (yeast) 3.788493 0.00288593

EPHB4 EPH receptor B4 3.785011 0.02475939

RNF32 ring finger protein 32 3.769771 0.00287434 estrogen receptor binding site associated,

EBAG9 antigen, 9 3.74778 0.04724541

SUPT7L suppressor of Ty 7 (S. cerevisiae)-like 3.739806 0.00867373

TRAPPC5 trafficking protein particle complex 5 3.738211 0.00696435

CCDC72 coiled-coil domain containing 72 3.729692 0.01918947 small nuclear R A activating complex,

SNAPC3 polypeptide 3, 50kDa 3.710914 0.04896459 tissue factor pathway inhibitor (lipoprotein-

TFPI associated coagulation inhibitor) 3.702241 0.01077594 protein kinase, cAMP-dependent, regulatory,

PRKAR1A type I, alpha (tissue specific extinguisher 1) 3.700851 0.00533686

CLSPN claspin homolog (Xenopus laevis) 3.690146 0.03121386

DCTD dCMP deaminase 3.684435 0.01782176

Clorf52 chromosome 1 open reading frame 52 3.680647 0.03117257

DPY19L4 dpy-19-like 4 (C. elegans) 3.663878 0.01007387

WAS/WASL interacting protein family,

WIPF1 member 1 3.660979 0.03597595

BIRC6 baculoviral IAP repeat-containing 6 3.656537 0.01040232

OTUD4 OTU domain containing 4 3.654642 0.01272272

FIP1L1 FIP1 like 1 (S. cerevisiae) 3.647902 0.0419402

KCMF1 potassium channel modulatory factor 1 3.644039 0.00877296

UGDH UDP-glucose 6-dehydrogenase 3.642483 0.02673765

5-aminoimidazole-4-carboxamide

ribonucleotide formyltransferase/IMP

ATIC cyclohydrolase 3.62996 0.02012458

ANKHD1-

EIF4EBP3 ANKHD1-EIF4EBP3 readthrough 3.615791 0.01331504

GPN2 GPN-loop GTPase 2 3.612946 0.00697294

Clor£21 chromosome 1 open reading frame 21 3.612657 0.00303055 protein phosphatase 2, regulatory subunit B,

PPP2R2A alpha 3.598525 0.00122241

TLK1 tousled-like kinase 1 3.593899 0.00771066 acyl-CoA dehydrogenase, C-4 to C-12

ACADM straight chain 3.582422 0.04333075

LON peptidase N-terminal domain and ring

LONRF2 finger 2 3.581772 0.0030919

Pleckstrin homology domain interacting

PHIP protein 3.581619 0.02464318 myeloid/lymphoid or mixed-lineage leukemia

MLL2 2 3.577065 0.00540534B1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value serine/arginine repetitive matrix 2 3.573755 0.00151055

RNA binding motif, single stranded

interacting protein 1 3.573282 0.02230447

Chromosome 7 open reading frame 23 3.571619 0.01456607 ring finger and WD repeat domain 2 3.566507 0.03374643 thioredoxin domain containing 9 3.559682 0.02318797 microtubule-actin crosslinking factor 1 3.557953 0.02131704 zinc finger protein 695 3.55649 0.00881763 dihydrolipoamide dehydrogenase 3.54755 0.03042714 transcription elongation regulator 1 3.545678 0.04063693

F-box and WD repeat domain containing 11 3.538266 0.01890564 heat shock 70kDa protein 4 3.534902 0.02613913 ganglioside induced differentiation associated

protein 2 3.533685 0.02896789

SUM01/sentrin/SMT3 specific peptidase 2 3.531085 9.19E-05 kinesin heavy chain member 2A 3.525546 0.04938074 acyl-CoA thioesterase 13 3.521514 0.0075496 guanine nucleotide binding protein-like 2

(nucleolar) 3.497915 0.01416406 polymerase (RNA) II (DNA directed)

polypeptide B, 140kDa 3.486012 0.01436831 chromosome 3 open reading frame 17 3.477404 0.00064013 uracil-DNA glycosylase 3.471251 0.01530078 zinc finger protein 259 3.457681 0.04340342 eukaryotic translation initiation factor 2-alpha

kinase 2 3.44408 0.03733034

Translocase of outer mitochondrial membrane

20 homolog (yeast) 3.442827 0.02955573 polymerase (RNA) II (DNA directed)

polypeptide J, 13.3kDa 3.428384 0.00412324

RAN binding protein 9 3.400619 0.00125475 transcription elongation factor A (SII), 1 3.391912 0.03816125 golgi phosphoprotein 3-Iike 3.388682 0.00624767 growth differentiation factor 15 3.377286 0.00294545

Junction-mediating and regulatory protein 3.374959 0.02396428 allograft inflammatory factor 1 -like 3.373096 0.0192261

KDEL (Lys-Asp-Glu-Leu) endoplasmic

reticulum protein retention receptor 2 3.368323 0.04949704 thyroid adenoma associated 3.355519 0.04286101 peptidylprolyl isomerase D 3.355162 0.01495089 myoneurin 3.346428 0.02219129 cytochrome c oxidase subunit VIIc 3.342622 0.00416541 Fas-activated serine/threonine kinase 3.341993 0.00627623 MOBl, Mps One Binder kinase activator-like

IB (yeast) 3.340311 0.04257654 protein phosphatase 1, regulatory (inhibitor)

subunit 10 3.336889 0.01923868 epithelial cell adhesion molecule 3.323857 0.00915246 S-phase kinase-associated protein 1 3.322104 0.00151204 RAB6C, member RAS oncogene family 3.31726 0.003515 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

RNF8 ring finger protein 8 3.3143 0.00922491

THOC7 THO complex 7 homolog (Drosophila) 3.308461 0.02961408

CEP63 centrosomal protein 63kDa 3.302191 0.01209246

CENPF centromere protein F, 350/400ka (mitosin) 3.299657 0.01890505

RTN4 Reticulon 4 3.298947 0.03604368 poly (ADP-ribose) polymerase family,

PARP14 member 14 3.294521 0.02209214

FNBP1L formin binding protein 1 -like 3.293076 0.01994225

SDCCAG1 serologically defined colon cancer antigen 1 3.288406 0.02022995

SWI/SNF-related, matrix-associated actin- dependent regulator of chromatin, subfamily

SMARCAD1 a, containing DEAD/H box 1 3.284105 0.04696085 protein kinase, AMP-activated, alpha 2

PRKAA2 catalytic subunit 3.270465 0.00135122

NCKAP1 NCK-associated protein 1 3.26989 0.00288743

PJA2 praja ring finger 2 3.267975 0.01980036

SP1 Spl transcription factor 3.262746 0.02261795 cleavage and polyadenylation specific factor

CPSF3 3, 73kDa 3.262621 0.03171989

Rho-associated, coiled-coil containing protein

ROCK1 kinase 1 3.257404 0.01235219

BRP44 brain protein 44 3.25371 0.00679127

SENP7 SUMOl/sentrin specific peptidase 7 3.253441 0.01090265

CDV3 CDV3 homolog (mouse) 3.247154 0.0416902

TRIM33 tripartite motif-containing 33 3.246718 3.37E-05

SH3 domain binding glutamic acid-rich

SH3BGRL protein like 3.242215 0.02599374 bromodomain adjacent to zinc finger domain,

BAZ1B IB 3.237744 0.02859738

AREG amphiregulin 3.237078 0.01549385

PDCD10 programmed cell death 10 3.236064 0.00460189

ETAA1 Ewing tumor-associated antigen 1 3.231263 0.04954475

DnaJ (Hsp40) homolog, subfamily C, member

DNAJC2 2 3.220929 0.01504643

EEF2 eukaryotic translation elongation factor 2 3.218901 0.03839601

DOC 7 dedicator of cytokinesis 7 3.215562 0.00207858

CAPN7 Calpain 7 3.213705 0.016063

ANAPC1 anaphase promoting complex subunit 1 3.20784 0.010159 ectonucleotide

ENPP1 pyrophosphatase/phosphodiesterase 1 3.205312 0.00421566 ubiquitin-like domain containing CTD

UBLCP1 phosphatase 1 3.200325 0.01796708 succinate dehydrogenase complex, subunit A,

SDHA flavoprotein (Fp) 3.197073 0.01758965 nuclear pore complex interacting protein-like

NPIPL3 3 3.190446 0.00688791

ZC3H13 zinc finger CCCH-type containing 13 3.190232 0.0483448

HAT1 histone acetyltransferase 1 3.188148 0.03486096

FTL ferritin, light polypeptide 3.184575 0.04393471

MAP4K3 mitogen-activated protein kinase kinase 3.183468 0.02370712

)B 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P

Change value

kinase kinase 3

MOBl, Mps One Binder kinase activator-like

MOB L3 3 (yeast) 3.180117 0.01515135

SDCCAG10 Serologically defined colon cancer antigen 10 3.169853 0.00021764

ANKRD12 ankyrin repeat domain 12 3.166422 0.03652241

FLJ361 16 hypothetical locus LOC388666 3.165658 0.01949919

ZNF138 zinc finger protein 138 3.162613 0.04255118

SQLE squalene epoxidase 3.159715 0.01084816

NOL10 nucleolar protein 10 3.156696 0.04048588

SNRPE small nuclear ribonucleoprotein polypeptide E 3.155035 0.02615373

LUC7L LUC7-like (S. cerevisiae) 3.148336 0.02414327

EHBP1 EH domain binding protein 1 3.145467 0.00658037

NAMPT nicotinamide phosphoribosyltransferase 3.139672 0.002413

NARS asparaginyl-tRNA synthetase 3.134902 0.01065447

RNF14 ring finger protein 14 3.131844 0.01179033

PFDN6 prefoldin subunit 6 3.126823 0.03269993

HMGA1 high mobility group AT-hook 1 3.126142 0.0074386

PRKCI protein kinase C, iota 3.11639 0.00319677

LASS6 LAG1 homolog, ceramide synthase 6 3.114282 0.02460543

C5orfl5 chromosome 5 open reading frame 15 3.104692 0.01730066

GOLIM4 golgi integral membrane protein 4 3.099776 0.03542058

ANLN anillin, actin binding protein 3.097471 0.03519748

SETD2 SET domain containing 2 3.092132 0.01030038

BAT2D1 BAT2 domain containing 1 3.08556 0.00103852

SF3B1 splicing factor 3b, subunit 1, 155kDa 3.079506 0.04359828

ERBB2IP erbb2 interacting protein 3.077623 0.01540714

DMXL1 Dmx-like 1 3.07451 1 0.00708549

ITPR1 inositol 1,4,5 -triphosphate receptor, type 1 3.07441 0.01539608

MEMOl Mediator of cell motility 1 3.070708 0.01237261

AKD2 N/A 3.069178 0.01556957

HIBCH 3-hydroxyisobutyryl-CoA hydrolase 3.065273 0.01688263

SOS1 son of sevenless homolog 1 (Drosophila) 3.063455 0.01573618

S100A1 1 S 100 calcium binding protein A 1 1 3.056371 0.02159673 guanine nucleotide binding protein (G

GNB1 protein), beta polypeptide 1 3.050983 0.02355176

CASQ1 calsequestrin 1 (fast-twitch, skeletal muscle) 3.045838 0.01434468

CYCS cytochrome c, somatic 3.041128 0.04095219

SP3 Sp3 transcription factor 3.033516 0.00452105

ZNF107 Zinc finger protein 107 3.029659 0.00307174

INPP5F inositol polyphosphate-5 -phosphatase F 3.026291 0.04307517

La ribonucleoprotein domain family, member

LARP7 7 3.023688 0.02499879

RERE arginine-glutamic acid dipeptide (RE) repeats 3.021721 0.00650595 ubiquitin protein ligase E3 component n-

UBR4 recognin 4 3.010769 0.01930641

ZFR zinc finger RNA binding protein 3.008818 0.04831955

SFRS18 splicing factor, arginine/serine-rich 18 2.999356 0.00938084

HPS3 Hermansky-Pudlak syndrome 3 2.997907 0.03836478

DPYD dihydropyrimidine dehydrogenase 2.997333 0.0006711

ITGB6 integrin, beta 6 2.989866 0.03976203

DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

CSRNP3 cysteine-serine-rich nuclear protein 3 0.00956

MORF4L2 mortality factor 4 like 2 0.03027653

ZMYM6 zinc finger, MYM-type 6 0.04641004 mutS homolog 2, colon cancer, nonpolyposis

MSH2 type 1 (E. coli) 0.03627096

PRMT6 protein arginine methyltransferase 6 0.02512139

TTC3 tetratricopeptide repeat domain 3 0.01436294 activating signal cointegrator 1 complex

ASCC3 subunit 3 0.00589593

RAD54L2 RAD54-like 2 (S. cerevisiae) 0.02651723

TP63 tumor protein p63 0.02945318

ZNF273 zinc finger protein 273 0.0417131

PUM2 pumilio homolog 2 (Drosophila) 0.02935277

CCNC cyclin C 0.00690543

ENY2 enhancer of yellow 2 homolog (Drosophila) 0.00070793

MRPL53 mitochondrial ribosomal protein L53 0.03432129 transient receptor potential cation channel,

TRPM6 subfamily M, member 6 2.939987 0.01854453

SMT3 suppressor of mif two 3 homolog 1 (S.

SUMOl cerevisiae) 0.01314778 EPM2AIP1 EPM2A (laforin) interacting protein 1 0.01328695 solute carrier family 9 (sodium/hydrogen

SLC9A1 exchanger), member 1 0.01354005

DNA cross-link repair IB (PS02 homolog, S.

DCLRE1B cerevisiae) 0.02550563 bromodomain adjacent to zinc finger domain,

BAZ2B 2B 0.02326191

ZC3H15 zinc finger CCCH-type containing 15 0.00317773

FERMT2 fermitin family homolog 2 (Drosophila) 0.00196358

SENP6 SUMOl/sentrin specific peptidase 6 0.01329545

SPOPL speckle-type POZ protein-like 0.03963368

ARMC10 armadillo repeat containing 10 0.03572479

ALCAM activated leukocyte cell adhesion molecule 0.03361215

IARS2 isoleucyl-tRNA synthetase 2, mitochondrial 0.02633645

PLS1 plastin 1 0.02158573

REEP5 receptor accessory protein 5 0.00852534

Clorfl l2 chromosome 1 open reading frame 112 0.02221652

Histidine acid phosphatase domain containing

HISPPD1 1 2.912902 0.04467233

UDP-N-acetyl-alpha-D- galactosamine:polypeptide N- acetylgalactosaminyltransferase 7 (GalNAc-

GALNT7 T7) 0.00233517 CRYGS crystallin, gamma S 0.01223416 BRAP BRCA1 associated protein 0.00707534 TCP1 t-complex 1 0.02939434 heterogeneous nuclear ribonucleoprotein U

HNRNPU (scaffold attachment factor A) 0.01266994

C7orf36 chromosome 7 open reading frame 36 0.00731727

RBBP6 retinoblastoma binding protein 6 0.03577545

DB l/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value malic enzyme 2, NAD(+)-dependent,

ME2 mitochondrial 2.886661 0.01 12677

ARID4A AT rich interactive domain 4 A (RBPl-like) 2.882351 0.00235678 malic enzyme 1 , NADP(+)-dependent,

ME1 cytosolic 2.879955 0.00454168

CDC2L6 Cell division cycle 2-like 6 (CDK8-like) 2.879457 0.04351182

DST dystonin 2.875358 0.04305397

MY018A myosin XVIIIA 2.875272 0.01734509

USP39 ubiquitin specific peptidase 39 2.866674 0.00731577

OSBPL11 oxysterol binding protein-like 11 2.865043 0.00441915

LTV1 LTV1 homolog (S. cerevisiae) 2.862159 0.03848354

MGC5590 hypothetical protein MGC5590 2.858516 0.00173223

BAIAP2L1 BAI1 -associated protein 2-like 1 2.85848 0.02297787

GREB1 GREB1 protein 2.856279 0.03013008

SWI/SNF related, matrix associated, actin

dependent regulator of chromatin, subfamily

SMARCC1 c, member 1 2.85378 0.03745351 signal transducer and activator of

STAT1 transcription 1, 91kDa 2.849821 0.01959205 ubiquitin specific peptidase 13 (isopeptidase

USP13 T-3) 2.848679 0.03625006

SASS6 spindle assembly 6 homolog (C. elegans) 2.845356 0.02224778

ZNF711 zinc finger protein 71 1 2.844816 0.02480081

SOX4 SRY (sex determining region Y)-box 4 2.841366 0.04188377 inturned planar cell polarity effector homolog

INTU (Drosophila) 2.839753 0.00781462

CCDC99 coiled-coil domain containing 99 2.834983 0.04509615

ZNF644 zinc finger protein 644 2.83475 0.02847176

UDP-Glc Ac:betaGal beta-l,3-N-

B3GNT2 acetylglucosaminyltransferase 2 2.830064 0.0205201 1

SMC3 structural maintenance of chromosomes 3 2.825491 0.03046467

TOP2B topoisomerase (DNA) II beta 180kDa 2.823094 0.02218412

FDFT1 farnesyl-diphosphate farnesyltransferase 1 2.822416 0.00648518

TBL1XR1 transducin (beta)-like 1 X-linked receptor 1 2.821702 0.01803827

RBAK RB-associated KRAB zinc finger 2.818775 0.04331016

TTLL5 tubulin tyrosine ligase-like family, member 5 2.815279 0.01605047

MLPH melanophilin 2.814576 0.02628659

DnaJ (Hsp40) homolog, subfamily B, member

DNAJB11 11 2.813687 0.01128434

WWC1 WW and C2 domain containing 1 2.813524 0.00083617

ZNF91 zinc finger protein 91 2.81138 0.02662892

ATPase, H+ transporting, lysosomal 70kDa,

ATP6V1A VI subunit A 2.81115 0.00180419

KIAA0746 KIAA0746 protein 2.80153 0.00643297

ArfGAP with SH3 domain, ankyrin repeat

ASAP1 and PH domain 1 2.799124 0.00462787

ANKHD1 ankyrin repeat and KH domain containing 1 2.79893 0.02854279 family with sequence similarity 184, member

FAM184A A 2.798923 0.00430328

HLTF helicase-like transcription factor 2.797219 0.02779826 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

Eukaryotic translation initiation factor 2A,

EIF2A 65kDa 2.797166 0.03413535 cyclin D binding myb-like transcription factor

DMTF1 1 2.794307 0.0338541

GPR125 G protein-coupled receptor 125 2.788845 0.04717651

RPL4 ribosomal protein L4 2.783907 0.03613678

YTHDC2 YTH domain containing 2 2.783345 0.00761701 growth arrest and DNA-damage-inducible,

GADD45A alpha 2.781856 0.04855598

USP34 ubiquitin specific peptidase 34 2.781149 0.03969944 family with sequence similarity 92, member

FAM92A1 Al 2.779772 0.00652292

GLA galactosidase, alpha 2.779352 0.00885348

SMC6 structural maintenance of chromosomes 6 2.772324 0.01058738

SKIL SKI-like oncogene 2.76743 0.01121972

SEC24A SEC24 family, member A (S. cerevisiae) 2.766295 0.0030784 minichromosome maintenance complex

MCM4 component 4 2.764255 0.01639846

RAS p21 protein activator (GTPase activating

RASA1 protein) 1 2.760016 0.02594615 v-ral simian leukemia viral oncogene

RALA homolog A (ras related) 2.759055 0.01615779

IWS1 IWS1 homolog (S. cerevisiae) 2.757355 0.01397659

ITSN2 intersectin 2 2.754509 0.03995086 nuclear undecaprenyl pyrophosphate synthase

NUS1 1 homolog (S. cerevisiae) 2.753898 0.02727482

CENPE centromere protein E, 312kDa 2.7536 0.0165937

COL7A1 collagen, type VII, alpha 1 2.753254 0.01516653

TTC17 tetratricopeptide repeat domain 17 2.750758 0.01252676 nuclear casein kinase and cyclin-dependent

NUCKS1 kinase substrate 1 2.746242 0.01149953

EBNA1BP2 EBNA1 binding protein 2 2.743401 0.02486242

C6orf203 chromosome 6 open reading frame 203 2.739947 0.02384998 chaperonin containing TCP1, subunit 5

CCT5 (epsilon) 2.739476 0.00602847

TPP1 tripeptidyl peptidase I 2.737982 0.01551944

GPR160 G protein-coupled receptor 160 2.733023 0.01181892

CCAAT/enhancer binding protein (C/EBP),

CEBPZ zeta 2.730668 0.04807979

SGOL1 shugoshin-like 1 (S. pombe) 2.730587 0.02367326

AFF1 AF4/FMR2 family, member 1 2.728118 0.01644025

Ras association (RalGDS/AF-6) and

RAPH1 pleckstrin homology domains 1 2.723734 0.01713881

NMBR neuromedin B receptor 2.7228 0.04557912 speedy homolog E8 (Xenopus laevis),

SPDYE8P pseudogene 2.721673 0.04081118

FLNB filamin B, beta 2.718523 0.02624732

RAD18 RAD 18 homolog (S. cerevisiae) 2.717404 0.03339343

ZNF595 zinc finger protein 595 2.717382 0.01742071

SFRS3 splicing factor, arginine/serine-rich 3 2.716461 0.03522487

)B1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

ARID IB AT rich interactive domain IB (SWIl-Iike) 2.716295 0.01486205 NOMOl NODAL modulator 1 2.71502 0.03140578 DEPDC6 DEP domain containing 6 2.714996 0.04184413

DEAD (Asp-Glu-Ala-Asp) box polypeptide

DDX39 39 2.714312 0.0446041 1 HIST2H2AC histone cluster 2, H2ac 2.712756 0.04657073 tRNA-yW synthesizing protein 3 homolog (S.

TYW3 cerevisiae) 2.711091 0.01835147

RBM47 RNA binding motif protein 47 2.709999 0.00456872

SC4MOL sterol-C4-methyl oxidase-like 2.708706 0.00099333

RWDD1 RWD domain containing 1 2.70643 0.03976333

PSIP1 PC4 and SFRS1 interacting protein 1 2.704173 0.00379656

NPNT nephronectin 2.690413 0.03429433

ZNHIT6 zinc finger, HIT type 6 2.688391 0.00045453

PPIC peptidylprolyl isomerase C (cyclophilin C) 2.684486 0.01273313

MRPS30 mitochondrial ribosomal protein S30 2.676295 0.02689152

RAB10 RAB10, member RAS oncogene family 2.675383 0.00826866

ATPase, H+ transporting, lysosomal 42kDa,

ATP6V1C1 VI subunit CI 2.667986 0.01481745

ATPase, H+ transporting, lysosomal 31kDa,

ATP6V1E1 VI subunit El 2.666607 0.02899272 polymerase (RNA) mitochondrial (DNA

POLRMT directed) 2.662838 0.0274167

EPRS glutamyl-prolyl-tRNA synthetase 2.662763 0.04513234

GPBP1L1 GC-rich promoter binding protein 1 -like 1 2.662573 0.04921046

DEAD (Asp-Glu-Ala-Asp) box polypeptide

DDX18 38 2.65979 0.0499591 1

TOPBP1 topoisomerase (DNA) II binding protein 1 2.659609 0.01512887

C7orf70 chromosome 7 open reading frame 70 2.658797 0.01611322

SMC5 structural maintenance of chromosomes 5 2.657527 0.031 10443

ZNF267 zinc finger protein 267 2.656681 0.02959774 sterile alpha motif and leucine zipper

ZAK containing kinase AZK 2.652971 0.01651627 PRLR prolactin receptor 2.652089 0.01578686 KIFAP3 kinesin-associated protein 3 2.651664 0.01016367 FOX03 forkhead box 03 2.649989 0.022331 12 eukaryotic translation initiation factor 2,

EIF2S2 subunit 2 beta, 38kDa 2.64701 0.04577479 excision repair cross-complementing rodent

ERCC5 repair deficiency, complementation group 5 2.64652 0.03234078 DLG1 discs, large homolog 1 (Drosophila) 2.644522 0.02181855 cell division cycle 2-like 2 (PITSLRE

CDC2L2 proteins) 2.640105 0.02399518

ZNF326 Zinc finger protein 326 2.639598 0.00776776

WDR60 WD repeat domain 60 2.639518 0.03968372 translocase of inner mitochondrial membrane

TIMM17A 17 homolog A (yeast) 2.638869 0.01019151

HDAC4 histone deacetylase 4 2.63716 0.04572722

GLS glutaminase 2.631911 0.03419736

NOTCH2NL Notch homolog 2 (Drosophila) N-terminal 2.630848 0.01387699

DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upreguiated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value like

OPA1 optic atrophy 1 (autosomal dominant) 2.629144 0.00144393 SYN1 synapsin I 2.625746 0.00855739

DnaJ (Hsp40) homolog, subfamily B, member

DNAJB14 14 2.625377 0.00031245

MBNL1 muscleblind-like (Drosophila) 2.616546 0.03413969

NUP155 nucleoporin 155kDa 2.614158 0.025106

7-Mar N/A 2.613053 0.01914936

C6orf97 chromosome 6 open reading frame 97 2.612996 0.01980769 HOOK2 hook homolog 2 (Drosophila) 2.611427 0.03199086 CCDC90A coiled-coil domain containing 90A 2.609805 0.02466542 PHC3 polyhomeotic homolog 3 (Drosophila) 2.608236 0.01227659 cell division cycle 73, Pafl/RNA polymerase

II complex component, homolog (S.

CDC73 cerevisiae) 2.602783 0.02198234

DAXX death-domain associated protein 2.601609 0.0097589

SF3B5 splicing factor 3b, subunit 5, lOkDa 2.593595 0.01024026

ANKRD17 ankyrin repeat domain 17 2.592918 0.00227678

ARF4 ADP-ribosylation factor 4 2.58944 0.01239217

HTT huntingtin 2.588494 0.04753706

FER fer (fps/fes related) tyrosine kinase 2.588405 0.03773494

SNX4 sorting nexin 4 2.588041 0.04103538 protein phosphatase 2, regulatory subunit B,

PPP2R2C gamma 2.586023 0.01065025 OLA1 Obg-like ATPase 1 2.585883 0.00413626 Clorfl35 chromosome 1 open reading frame 135 2.585302 0.03438371 RNF216 ring finger protein 216 2.584577 0.01318104 far upstream element (FUSE) binding protein

FUBP1 1 2.584276 0.02883731 WDFY1 WD repeat and FYVE domain containing 1 2.584271 0.02398677 minichromosome maintenance complex

MCM3AP component 3 associated protein 2.583767 0.01780226

TRAF family member-associated NFKB

TANK activator 2.583302 0.02722171

ACBD3 acyl-CoA binding domain containing 3 2.576254 0.02388443

THBS3 thrombospondin 3 2.575883 0.01390215

CXXC5 CXXC finger 5 2.57271 0.01699583

CSNK1A1 casein kinase 1 , alpha 1 2.565332 0.02008984

YTHDC1 YTH domain containing 1 2.564672 0.04083437

B double prime 1, subunit of R A

polymerase III transcription initiation factor

BDP1 IIIB 2.563562 0.0098413 catenin (cadherin-associated protein), alpha 1 ,

CTNNA1 102kDa 2.563386 0.01924656

PHF14 PHD finger protein 14 2.562435 0.00856813

YEATS2 YEATS domain containing 2 2.561844 0.03698105 ribosomal RNA processing 15 homolog (S.

RRP15 cerevisiae) 2.558002 0.00434063

REV3-like, catalytic subunit of D A

REV3L polymerase zeta (yeast) 2.557663 0.00922597

DB l/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

SRP72 signal recognition particle 72kDa 2.557519 0.02100872

PKP4 plakophilin 4 2.557151 0.00914

DCN1, defective in cullin neddylation 1,

DCU 1D4 domain containing 4 (S. cerevisiae) 2.556521 0.02739626 caspase 2, apoptosis-related cysteine

CASP2 peptidase 2.555916 0.0459927

UTRN utrophin 2.55405 0.00844229

BAT2 HLA-B associated transcript 2 2.553422 0.02006314 polymerase (RNA) II (DNA directed)

POLR2J2 polypeptide J2 2.550879 0.00054071

CLGN calmegin 2.549584 0.0097492

FAM45B family with sequence similarity 45, member B 2.546071 0.0026172

SF S5 splicing factor, arginine/serine-rich 5 2.545075 0.02950629

TIP41, TOR signaling pathway regulator-like

TIPRL (S. cerevisiae) 2.541724 0.03186236

C3orf57 chromosome 3 open reading frame 57 2.540082 0.0094237

RNGTT RNA guanylyltransferase and 5'-phosphatase 2.538319 0.03659254

USP46 ubiquitin specific peptidase 46 2.536854 0.0195821 1

DDX1 DEAD (Asp-Glu-Ala-Asp) box polypeptide 1 2.534563 0.00605707 proteasome (prosome, macropain) 26S

PSMD14 subunit, non-ATPase, 14 2.533865 0.02390241

KRIT1 KRIT1, ankyrin repeat containing 2.533715 0.00341833

GULP, engulfment adaptor PTB domain

GULP1 containing 1 2.533211 0.00031662 ubiquitin protein ligase E3 component n-

UBR2 recognin 2 2.529112 0.02522009

CLK4 CDC-like kinase 4 2.519794 0.04344857 protein phosphatase 2, regulatory subunit B',

PPP2R5C gamma 2.51958 0.01802986

NOTCH3 Notch homolog 3 (Drosophila) 2.518418 0.02050312

CUL3 cullin 3 2.512555 0.03000904

KLHL20 kelch-like 20 (Drosophila) 2.511604 0.04625872

PLK4 polo-like kinase 4 (Drosophila) 2.510571 0.02626713 v-raf-1 murine leukemia viral oncogene

RAF1 homolog 1 2.510375 0.04663954

CD2AP CD2-associated protein 2.509456 0.04171078

HSF2 heat shock transcription factor 2 2.506697 0.02377126 family with sequence similarity 98, member

FAM98A A 2.506122 0.01 113668

BTF3 basic transcription factor 3 2.504564 0.04945883

TLN2 talin 2 2.504179 0.01450135

ANKRD36B ankyrin repeat domain 36B 2.501792 0.01895399

ACTR3 ARP3 actin-related protein 3 homolog (yeast) 2.500061 0.02540777

MOB 1 , Mps One Binder kinase activator-like

MOBKL1A 1A (yeast) 2.495315 0.01061014

DEAD (Asp-Glu- Ala-Asp) box polypeptide

DDX55 55 2.494592 0.02799053

TRIP12 thyroid hormone receptor interactor 12 2.494017 0.03689934

ARID4B AT rich interactive domain 4B (RBPl-like) 2.49337 0.03529843

NLN neurolysin (metallopeptidase M3 family) 2.492964 0.01595546 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P

value

USP3 ubiquitin specific peptidase 3 2.491308 0.03275649

MBD4 methyl-CpG binding domain protein 4 2.48954 0.01907074 pituitary tumor-transforming 1 interacting

PTTG1IP protein 2.486349 0.0297117 brain and reproductive organ-expressed

BRE (TNFRSF1A modulator) 2.484356 0.00442756

KDM1 N/A 2.481278 0.00750192

QSER1 glutamine and serine rich 1 2.475907 0.0242896

MRPL18 Mitochondrial ribosomal protein LI 8 2.474773 0.01902557 glycerol-3-phosphate dehydrogenase 2

GPD2 (mitochondrial) 2.471884 0.03872717

PHACTR2 phosphatase and actin regulator 2 2.470462 0.01247884 protein phosphatase 1 , catalytic subunit, beta

PPP1CB isozyme 2.468217 0.04691501

BCL9 B-cell CLL/lymphoma 9 2.457588 0.01401656 recombination signal binding protein for

RBPJ immunoglobulin kappa J region 2.456823 0.03872586

Transient receptor potential cation channel,

TRPM8 subfamily M, member 8 2.455114 0.00945206

RSBN1 round spermatid basic protein 1 2.453006 0.00130387

USP33 ubiquitin specific peptidase 33 2.452053 0.01813434

NEB nebulin 2.449909 0.03071673

CTAGE5 CTAGE family, member 5 2.447423 0.03469659

GPBP1 GC-rich promoter binding protein 1 2.445774 0.03848269

AZI2 5-azacytidine induced 2 2.445213 0.03482439 tRNA-yW synthesizing protein 1 homolog (S.

TYW1 cerevisiae) 2.445006 0.0446882

FOXJ3 forkhead box J3 2.441988 0.01508939

BXDC5 Brix domain containing 5 2.437638 0.01014076

SGOL2 shugoshin-like 2 (S. pombe) 2.436637 0.00564431

PTPRF interacting protein, binding protein 1

PPFIBP1 (liprin beta 1) 2.431492 0.03837188 melanoma inhibitory activity family, member

MIA3 3 2.431448 0.03171622

SDC2 syndecan 2 2.42999 0.04326632

WHSC1 Wolf-Hirschhorn syndrome candidate 1 2.429055 0.01584686

LRRC16A leucine rich repeat containing 16A 2.428642 0.00030284

TMEM106B transmembrane protein 106B 2.426336 0.00185522

SATB2 SATB homeobox 2 2.426291 0.00519515

CLIC4 chloride intracellular channel 4 2.420927 0.04525662

ARMC8 armadillo repeat containing 8 2.420129 0.02913344

USP48 ubiquitin specific peptidase 48 2.418434 0.03846682

RSRC2 arginine/serine-rich coiled-coil 2 2.415397 0.0414388

RNF149 ring finger protein 149 2.415338 0.00678303

CDCA2 Cell division cycle associated 2 2.414986 0.04014665

Split hand/foot malformation (ectrodactyly)

SHFM1 type 1 2.411671 0.02417581

ENOPH1 enolase-phosphatase 1 2.411171 0.01301109

PFN2 profilin 2 2.410395 0.008569

RDBP RD RNA binding protein 2.410004 0.01193128 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

TACSTD2 tumor-associated calcium signal transducer 2 2.409326 0.03705571

WW domain containing E3 ubiquitin protein

WWP1 ligase 1 2.407783 0.01240765

TAGLN2 transgelin 2 2.407305 0.03670214

COPG coatomer protein complex, subunit gamma 2.406812 0.03959455 nucleophosmin (nucleolar phosphoprotein

NPM1 B23, numatrin) 2.406641 0.01665033

UDP-glucose ceramide glucosyltransferase-

UGCGL1 like 1 2.402575 0.00193798 hexose-6-phosphate dehydrogenase (glucose

H6PD 1 -dehydrogenase) 2.401089 0.03727115 myeloid/lymphoid or mixed-lineage leukemia

MLL3 3 2.397088 0.00923063

SEC63 SEC63 homolog (S. cerevisiae) 2.3961 0.00304391

E74-like factor 2 (ets domain transcription

ELF2 factor) 2.39587 0.00551064 eukaryotic translation elongation factor 1

EEF1E1 epsilon 1 2.394143 0.01844291

CREG1 cellular repressor of ElA-stimulated genes 1 2.392246 0.02861787 IAA0922 KIAA0922 2.388858 0.0279595

CLIPl CAP-GLY domain containing linker protein 1 2.384416 0.03137165

FAM3C family with sequence similarity 3, member C 2.383435 0.00661523

CCNL1 Cyclin LI 2.383196 0.03715368

HHLA3 HERV-H LTR-associating 3 2.381252 0.04036587 nascent-polypeptide-associated complex

N AC API alpha polypeptide pseudogene 1 2.380781 0.03679794

C2orf49 chromosome 2 open reading frame 49 2.380543 0.03557126

SDC3 Syndecan 3 2.377861 0.01536423

C7orf30 chromosome 7 open reading frame 30 2.375592 0.00732418

C7orf60 chromosome 7 open reading frame 60 2.375581 0.0051832

RAB1A RAB1 A, member RAS oncogene family 2.373609 0.04191459

TOPORS Topoisomerase I binding, arginine/serine-rich 2.371666 0.03979896

DHX9 DEAH (Asp-Glu-Ala-His) box polypeptide 9 2.370434 0.0025908

RHBDF2 rhomboid 5 homolog 2 (Drosophila) 2.366587 0.03932245 low density lipoprotein receptor-related

LRP1 protein 1 2.365807 0.00104357

ATPase, Ca++ transporting, type 2C, member

ATP2C1 1 2.36579 0.00861049

EXOSC10 exosome component 10 2.36316 0.0220261

ZBTB11 zinc finger and BTB domain containing 11 2.362742 0.01423144

DMKN dermokine 2.360421 0.03954072

USOl vesicle docking protein homolog

USOl (yeast) 2.359821 0.02226331

AHCTF1 AT hook containing transcription factor 1 2.359072 0.00613172

INTS4 integrator complex subunit 4 2.358132 0.03508975

RIOK1 RIO kinase 1 (yeast) 2.354234 0.01010178 metal response element binding transcription

MTF2 factor 2 2.354146 0.0214147 poly (ADP-ribose) polymerase family,

PARP8 member 8 2.353916 0.02193377 1/ 69437516.1 Supplemental Tabic 1. Gene Transcripts Upreguiated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

C3orf49 chromosome 3 open reading frame 49 2.35178 0.0201645 glutaminyl-tRNA synthase (glutamine-

QRSL1 hydrolyzing)-like 1 2.349048 0.02832035

V-myc myelocytomatosis viral oncogene

MYC homolog (avian) 2.348995 0.02396725

ZBTB41 zinc finger and BTB domain containing 41 2.345229 0.04085399 procollagen-lysine, 2-oxoglutarate 5-

PLOD2 dioxygenase 2 2.345036 0.02011477 family with sequence similarity 119, member

FAM1 19A A 2.33913 0.0058591

KIF2C kinesin family member 2C 2.338823 0.02722488

RAB7A RAB7A, member RAS oncogene family 2.338591 0.00328242

NSU 5 NOP2/Sun domain family, member 5 2.337845 0.03644286

CD46 molecule, complement regulatory

CD46 protein 2.333239 0.02096143

CEP135 centrosomal protein 135kDa 2.333179 0.01103042 thioredoxin domain containing 5

TXNDC5 (endoplasmic reticulum) 2.332472 0.00547594

Leol, Pafl/R A polymerase II complex

LEOl component, homolog (S. cerevisiae) 2.332126 0.02737226

WDSOF1 WD repeats and SOF1 domain containing 2.33082 0.00345726

CTBS chitobiase, di-N-acetyl- 2.330361 0.02094886

CEP 170 centrosomal protein 170kDa 2.328966 0.0312379

AK2 adenylate kinase 2 2.32623 0.04153099

ERRFIl ERBB receptor feedback inhibitor 1 2.325127 0.01808355

MREG melanoregulin 2.32298 0.02918713

ZNF184 zinc finger protein 184 2.320743 0.03883664

CHMP4C chromatin modifying protein 4C 2.319309 0.0139899

ZFYVE9 zinc finger, FYVE domain containing 9 2.318986 0.00076831

WDR34 WD repeat domain 34 2.318692 0.03570756 protein tyrosine phosphatase, non-receptor

type 13 (APO-1/CD95 (Fas)-associated

ΡΤΡΝΪ3 phosphatase) 2.316902 0.03008615

SH3 -domain binding protein 5 (BTK-

SH3BP5 associated) 2.315352 0.00347119

RHOB ras homolog gene family, member B 2.314938 0.00360295 polycystic kidney disease 2 (autosomal

PKD2 dominant) 2.312196 0.00272198 eukaryotic translation initiation factor 4

EIF4G3 gamma, 3 2.311806 0.03563678 protein tyrosine phosphatase, non-receptor

PTPN22 type 22 (lymphoid) 2.310831 0.03701475

UBE2C ubiquitin-conjugating enzyme E2C 2.309809 0.03275616

ATP-binding cassette, sub-family F (GCN20),

ABCF1 member 1 2.309064 0.04908242 acyl-CoA synthetase long-chain family

ACSL3 member 3 2.306145 0.01677941

GPR126 G protein-coupled receptor 126 2.302486 0.01624519

RUFY1 RUN and FYVE domain containing 1 2.302149 0.00032141

RCC2 regulator of chromosome condensation 2 2.300055 0.04480846

B U 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

MRPL3 mitochondrial ribosomal protein L3 2.298195 0.03084317

BXDC1 Brix domain containing 1 2.297265 0.02647709

PCBP4 poly(rC) binding protein 4 2.297239 0.0480034

FKBP3 FK506 binding protein 3, 25kDa 2.294143 0.00750185

CRELD1 cysteine-rich with EGF-like domains 1 2.292013 0.01054939

IMMT inner membrane protein, mitochondrial 2.291678 0.02551435

TRBC2 T cell receptor beta constant 2 2.291039 0.01815739

ABI2 abl-interactor 2 2.290111 0.04912702

Phosphatidylinositol 4-kinase, catalytic, alpha

PI4KAP2 pseudogene 2 2.287821 0.01409133

FYTTD1 forty-two-three domain containing 1 2.286731 0.02369016

THEM4 thioesterase superfamily member 4 2.286356 0.042979

ZNF638 zinc finger protein 638 2.285398 0.02130371

SLC25A46 solute carrier family 25, member 46 2.284449 0.00388639

LR C9 N/A 2.28276 0.00475323 establishment of cohesion 1 homo log 1 (S.

ESCOl cerevisiae) 2.280783 0.02158678 chromodomain helicase DNA binding protein

CHD1 1 2.27918 0.02465009 protein phosphatase 1 , regulatory (inhibitor)

PPP1R12A subunit 12A 2.277063 0.04329455

PTPRK protein tyrosine phosphatase, receptor type, K 2.273966 0.01124848

ACVR1 activin A receptor, type I 2.273641 0.00180738

SFRS12 splicing factor, arginine/serine-rich 12 2.271856 0.01864358 protein tyrosine phosphatase type IVA,

PTP4A1 member 1 2.270167 0.00847749 transforming, acidic coiled-coil containing

TACC3 protein 3 2.268162 0.01045492 general transcription factor IIH, polypeptide

GTF2H2 2, 44kDa 2.267553 0.04759197

FK506 binding protein 12-rapamycin

FRAP1 associated protein 1 2.265502 0.0117058

SF3B2 splicing factor 3b, subunit 2, 145kDa 2.264361 0.01 19544

RPTOR independent companion of MTOR,

RICTOR complex 2 2.26423 0.02269076

RNF115 ring finger protein 1 15 2.263794 0.0345823

TCEA3 transcription elongation factor A (SII), 3 2.261769 0.00150668

RNF168 ring finger protein 168 2.260016 0.02333929 transient receptor potential cation channel,

TRPM5 subfamily M, member 5 2.259096 0.00420324

7-Sep N/A 2.256637 0.0285657

JARID2 jumonji, AT rich interactive domain 2 2.254895 0.01620599 nuclear receptor subfamily 1 , group D,

NR1D2 member 2 2.254522 0.03475131 general transcription factor IIIC, polypeptide

GTF3C6 6, alpha 35kDa 2.249268 0.04271905 pleckstrin homology domain containing,

PLEKHF2 family F (with FYVE domain) member 2 2.24915 0.03034525

CDC42 binding protein kinase alpha (DMPK-

CDC42BPA like) 2.24623 0.00937014 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulatcd by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

PACRGL PARK2 co-regulated-like 2.24344 0.01105086

BTF3L4 basic transcription factor 3 -like 4 2.243375 0.03396626

MTX1 metaxin 1 2.240865 0.04610751

PRP40 pre-mRNA processing factor 40

PRPF40A homolog A (S. cerevisiae) 2.237862 0.03098713

TBC1 (tre-2/USP6, BUB2, cdcl6) domain

TBC1D1 family, member 1 2.235136 0.00238682

TBC1D14 TBC1 domain family, member 14 2.23396 0.00059499 solute carrier family 6 (neurotransmitter

SLC6A6 transporter, taurine), member 6 2.233084 0.01778543

ATPase, Na+/K+ transporting, alpha 1

ATP1A1 polypeptide 2.231444 0.0033896

PANK4 pantothenate kinase 4 2.230306 0.01598754

MYEOV2 myeloma overexpressed 2 2.229539 0.048704

DEPDC1 DEP domain containing 1 2.22899 0.03843419

La ribonucleoprotein domain family, member

LARP2 2 2.228433 0.01018392 mitogen-activated protein kinase kinase

MAP3K6 kinase 6 2.227417 0.03751421 chaperonin containing TCP1, subunit 6 A

CCT6A (zeta 1) 2.226682 0.02645749 golgi-associated PDZ and coiled-coil motif

GOPC containing 2.226256 0.03894013

SCARB2 scavenger receptor class B, member 2 2.225542 0.00468326

KPNA1 karyopherin alpha 1 (importin alpha 5) 2.225491 0.02352899 IAA1967 KIAA1967 2.224672 0.00664399

RANBP2 RAN binding protein 2 2.224515 0.03771105

C6orfl06 chromosome 6 open reading frame 106 2.223548 0.03053372

JTB jumping translocation breakpoint 2.221965 0.01933583 oxidoreductase NAD-binding domain

OXNAD1 containing 1 2.217194 0.04995544

C2orf3 chromosome 2 open reading frame 3 2.214359 0.03959238

DARS2 aspartyl-tRNA synthetase 2, mitochondrial 2.213768 0.02672262

FBX09 F-box protein 9 2.212575 0.00029593

HNR PK heterogeneous nuclear ribonucleoprotein K 2.212481 0.01145842

KIF15 kinesin family member 15 2.211394 0.04216057

ATR ataxia telangiectasia and Rad3 related 2.210707 0.03297327

ZC3H11A zinc finger CCCH-type containing 11 A 2.210603 0.01108381

SYCP2L synaptonemal complex protein 2-like 2.21008 0.02356155

STK10 serine/threonine kinase 10 2.209612 0.01624999

DEAH (Asp-Glu-Ala-His) box polypeptide

DHX36 36 2.209532 0.01561221 small nuclear ribonucleoprotein polypeptide

SNRPG G 2.208125 0.01762589

SWI/SNF related, matrix associated, actin

dependent regulator of chromatin, subfamily

SMARCC2 c, member 2 2.20742 0.04232519 hyaluronan-mediated motility receptor

JIMMR (RHAMM) 2.206968 0.02153581

TRRAP transformation/transcription domain- 2.204836 0.00948173

B 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upreguiated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value associated protein

USP1 ubiquitin specific peptidase 1 2.204293 0.02425862

3-hydroxy-3-methylglutaryl-CoA synthase 1

HMGCS1 (soluble) 2.202971 0.04764687

LanC lantibiotic synthetase component C-like

LANCL3 3 (bacterial) 2.202319 0.01353871

PPIE peptidylprolyl isomerase E (cyclophilin E) 2.202103 0.03374511

ADP-ribosylation factor guanine nucleotide-

ARFGEF1 exchange factor l(brefeldin A-inhibited) 2.200694 0.03552716

CCDC104 coiled-coil domain containing 104 2.200303 0.03411197

STT3, subunit of the

oligosaccharyltransferase complex, homolog

STT3B B (S. cerevisiae) 2.199036 0.03541682

ITNRNPR heterogeneous nuclear ribonucleoprotein R 2.197778 0.04812168

SFRS1 1 splicing factor, arginine/serine-rich 11 2.197102 0.03128218

ZNF281 zinc finger protein 281 2.19509 0.01743985

EXOC1 exocyst complex component 1 2.193714 0.01664327

GTF2I general transcription factor Hi 2.193136 0.01310569 mutL homolog 1, colon cancer, nonpolyposis

MLH1 type 2 (E. coli) 2.1927 0.00460208

2-Sep N/A 2.191638 0.04509541

RNF4 ring finger protein 4 2.190935 0.04556102

BCL2/adenovirus E1B 19kDa interacting

BNIP3L protein 3 -like 2.190636 0.02883592 ubiquitin-conjugating enzyme E2K (UBC1

UBE2K homolog, yeast) 2.187646 0.04056877

COG5 component of oligomeric golgi complex 5 2.18755 0.01867518

LAMC1 laminin, gamma 1 (formerly LAMB2) 2.186259 0.01464433 suppressor of defective silencing 3 homolog

SUDS3 (S. cerevisiae) 2.184154 0.02450571

TMEM70 transmembrane protein 70 2.18302 0.01154643

SMYD2 SET and MYND domain containing 2 2.182951 0.03899734

LHB luteinizing hormone beta polypeptide 2.182615 0.01722195

TMEM173 transmembrane protein 173 2.180848 0.03326728 v-myb myeloblastosis viral oncogene

MYB homolog (avian) 2.180272 0.03642402

WR IP1 Werner helicase interacting protein 1 2.178547 0.0355725

UDP glucuronosyltransferase 1 family,

UGT1A1 polypeptide Al 2.177598 0.02829903

HSPA1L heat shock 70kDa protein 1 -like 2.176998 0.0201304

MAK16 MAK16 homolog (S. cerevisiae) 2.173803 0.00414123

N-acyl phosphatidylethanolamine

NAPEPLD phospholipase D 2.173229 0.02614538

SBDS Shwachman-Bodian-Diamond syndrome 2.17005 0.01655807

SEC62 SEC62 homolog (S. cerevisiae) 2.169831 0.04532519

HNRNPA3 heterogeneous nuclear ribonucleoprotein A3 2.168628 0.02389785

WDR67 WD repeat domain 67 2.167434 0.00446287

ATF7 activating transcription factor 7 2.166594 0.03631358

PRP4 pre-mRNA processing factor 4

PRPF4B homolog B (yeast) 2.165609 0.03223181

)B1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P

value

SEC31A SEC31 homolog A (S. cerevisiae) 2.1652 0.02487707

SNX14 sorting nexin 14 2.165102 0.00817069

TPRXL tetra-peptide repeat homeobox-like 2.16455 0.03297741

5-methyltetrahydrofolate -homocysteine

MTR methyltransferase reductase 2.163555 0.00590251 small nuclear ribonucleoprotein 27kDa

SNR P27 (U4/U6.U5) 2.162445 0.00100547

DCTN6 dynactin 6 2.162306 0.01377062 bromodomain and WD repeat domain

BRWD1 containing 1 2.160193 0.03029809

ADP-ribosylation factor GTPase activating

ARFGAP1 protein 1 2.158847 0.00933169

OSTC oligosaccharyltransferase complex subunit 2.158351 0.04226552 uveal autoantigen with coiled-coil domains

UACA and ankyrin repeats 2.154989 0.04375681

SEC24B SEC24 family, member B (S. cerevisiae) 2.151645 0.01992121

MYOIB myosin IB 2.15138 0.0258798

RBM28 RNA binding motif protein 28 2.14976 0.01120596 ubiquitin-conjugating enzyme E2E 1

UBE2E1 (UBC4/5 homolog, yeast) 2.148221 0.02655605

DUS4L dihydroundine synthase 4-like (S. cerevisiae) 2.144957 0.0021074 ubiquitin protein ligase E3 component n-

UBR3 recognin 3 (putative) 2.144184 0.04480702

Clorf95 chromosome 1 open reading frame 95 2.144175 0.02655454

NIF3 NGG1 interacting factor 3-like 1 (S.

NIF3L1 pombe) 2.141869 0.03166882

ZSWIM1 zinc finger, SWIM- type containing 1 2.139669 0.02872817

Proteasome (prosome, macropain) 26S

PSMD6 subunit, non-ATPase, 6 2.138274 0.03380946 prostate transmembrane protein, androgen

PMEPA1 induced 1 2.137851 0.04356498

UBXN4 UBX domain protein 4 2.134574 0.03656636

RNA (guanine-9-) methyltransferase domain

RG9MTD1 containing 1 2.132406 0.00135426

WDFY3 WD repeat and FYVE domain containing 3 2.132311 0.02184892 eukaryotic translation initiation factor 2-alpha

EIF2AK1 kinase 1 2.131712 0.04290871

PELO pelota homolog (Drosophila) 2.130176 0.03684364

UNC50 unc-50 homolog (C. elegans) 2.129257 0.03952495

RHBDD2 rhomboid domain containing 2 2.12889 0.0188589

Adaptor protein, phosphotyrosine interaction,

APPL1 PH domain and leucine zipper containing 1 2.127615 0.02011287

CSNK1G3 casein kinase 1, gamma 3 2.125913 0.04493096

ZNF514 zinc finger protein 514 2.123776 0.0050203 tyrosine 3-monooxygenase/tryptophan 5- monooxygenase activation protein, theta

YWHAQ polypeptide 2.122941 0.02980982

ESF1, nucleolar pre-rRNA processing

ESF1 protein, homolog (S. cerevisiae) 2.119551 0.0214415

ANXA5 annexin A5 2.1 17766 0.027320881/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Chan; value

AFTPH aftiphilin 2.117749 0.03049236

RFC1 replication factor C (activator 1) 1, 145kDa 2.116992 0.00583182

La ribonucleoprotein domain family, member

LARP1 1 2.1 16245 0.04277522 thioredoxin domain containing 12

TXNDC12 (endoplasmic reticulum) 2.113176 0.01256333 protein phosphatase 2, regulatory subunit B',

PPP2R5A alpha 2.11295 0.00397717 human immunodeficiency virus type I

HIVEP2 enhancer binding protein 2 2.112354 0.03843608

POGZ pogo transposable element with ZNF domain 2.111922 0.03641985

UBA6 ubiquitin-like modifier activating enzyme 6 2.111562 0.00068623

MCHR2 melanin-concentrating hormone receptor 2 2.111065 0.02992327 trimethylguanosine synthase homolog (S.

TGS1 cerevisiae) 2.1 10798 0.00993222 small nuclear ribonucleoprotein polypeptide

SNRPA A 2.110065 0.04567239

SLC44A4 solute carrier family 44, member 4 2.109894 0.00186453

ZNF354A zinc finger protein 354A 2.109637 0.03065182

KLHL12 kelch-like 12 (Drosophila) 2.109343 0.00422031

B3GALNT2 beta-1 ,3-N-acetylgalactosaminyltransferase 2 2.107978 0.02873171

KIAA0182 KIAA0182 2.105678 0.00027903 dual serine/threonine and tyrosine protein

DSTYK kinase 2.102727 0.02592546

FUS interacting protein (serine/arginine-rich)

FUSIP1 1 2.102131 0.02330608

FAM13B family with sequence similarity 13, member B 2.10149 0.01852387 deoxynucleotidyltransferase, terminal,

DNTTIP2 interacting protein 2 2.099591 0.00861354

TJP2 tight junction protein 2 (zona occludens 2) 2.09871 1 0.01329586

RAP1GDS1 RAP1, GTP-GDP dissociation stimulator 1 2.096922 0.01049954 transmembrane 9 superfamily protein member

TM9SF4 4 2.095538 0.01990121

ZNF642 zinc finger protein 642 2.094272 0.03423278

KDM3B lysine (K)-specific demethylase 3B 2.094253 0.01362526

TUBA4B tubulin, alpha 4b (pseudogene) 2.093234 0.04030352

CLCNKB chloride channel Kb 2.091022 0.00559579

SMAP1 small ArfGAP 1 2.089852 0.00484321 discoidin, CUB and LCCL domain containing

DCBLD2 2 2.089302 0.04770933

FBXOl l F-box protein 11 2.088507 0.0217985

RBM15 RNA binding motif protein 15 2.087109 0.02343943

FN1 fibronectin 1 2.086645 0.02269285 regulation of nuclear pre-mRNA domain

RPRD2 containing 2 2.084123 0.04290636

OSBPL7 oxysterol binding protein-like 7 2.083875 0.04973404

PDS5, regulator of cohesion maintenance,

PDS5A homolog A (S. cerevisiae) 2.082805 8.27E-05

RPL19 ribosomal protein LI 9 2.082173 0.00150615

E2F3 E2F transcription factor 3 2.079912 0.02457361 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value leukocyte immunoglobulin-like receptor,

LILRA6 subfamily A (with TM domain), member 6 2.078825 0.02342479

I TS3 integrator complex subunit 3 2.076955 0.03874923

YIPF5 Yipl domain family, member 5 2.076073 0.03670269

HIST1H2BK histone cluster 1 , H2bk 2.075114 0.0466658 eukaryotic translation elongation factor 1 beta

EEF1B2 2 2.074873 0.00215122

ZNF800 zinc finger protein 800 2.074305 0.00349819

ZMYM2 zinc finger, MYM-type 2 2.074188 0.03424201

C10orfH8 chromosome 10 open reading frame 118 2.073993 0.04425112 family with sequence similarity 105, member

FAM105B B 2.072397 0.02274536

KDM3A lysine (K)-specific demethylase 3 A 2.071821 0.01219305 proteoglycan 2, bone marrow (natural killer

cell activator, eosinophil granule major basic

PRG2 protein) 2.071409 0.00277223

DCDC2 doublecortin domain containing 2 2.070271 0.02643862

TET2 tet oncogene family member 2 2.068443 0.02470754 mitogen-activated protein kinase kinase

MAP4 4 kinase kinase 4 2.068156 0.00788839

TFB2M transcription factor B2, mitochondrial 2.068018 0.03582113 protein phosphatase 1 , regulatory (inhibitor)

PPP1R15B subunit 15B 2.067971 0.00766167

MESDC1 mesoderm development candidate 1 2.066987 0.01694928

GJA9 gap junction protein, alpha 9, 59kDa 2.065205 0.01443866

HTATSF1 HIV- 1 Tat specific factor 1 2.065056 0.04590911 family with sequence similarity 91, member

FAM91A1 Al 2.064779 0.04939123

TAGAP T-cell activation GTPase activating protein 2.064374 0.04064409

GPATCH1 G patch domain containing 1 2.064054 0.00269694

LRRC40 leucine rich repeat containing 40 2.063667 0.0216401

TTC1 tetratricopeptide repeat domain 1 2.063528 0.04752468 transient receptor potential cation channel,

TRPM7 subfamily M, member 7 2.062142 0.04289137

KLK12 kallikrein-related peptidase 12 2.061609 0.04666684

SEC 13 SEC 13 homolog (S. cerevisiae) 2.059411 0.00145595 origin recognition complex, subunit 2-like

ORC2L (yeast) 2.058017 0.0413684

NAV2 neuron navigator 2 2.05691 0.03319842

C4orf7 chromosome 4 open reading frame 7 2.055779 0.04168687

ARP3 actin-related protein 3 homolog B

ACTR3B (yeast) 2.053373 0.03786555

BAIAP2 B All -associated protein 2 2.053273 0.04228088

IDH1 isocitrate dehydrogenase 1 (NADP+), soluble 2.052557 0.02683413 ubiquitin-conjugating enzyme E2E 2

UBE2E2 (UBC4/5 homolog, yeast) 2.050191 0.00816482

EIF4E eukaryotic translation initiation factor 4E 2.049544 0.0267098 dolichyl-diphosphooligosaccharide-protein

DDOST glycosyltransferase 2.049205 0.03395848

BAX BCL2-associated X protein 2.048317 0.039567

IB 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value intraflagellar transport 140 homolog

IFT140 (Chlamydomonas) 2.04779 0.03465379

ZNF440 zinc finger protein 440 2.045831 0.01031447

TMEM39B transmembrane protein 39B 2.045654 0.00057521

HEATR1 HEAT repeat containing 1 2.045248 0.04601141

M-phase phosphoprotein 10 (U3 small

MPHOSPH10 nucleolar ribonucleoprotein) 2.045137 0.0353561

NGLY1 N-glycanase 1 2.04495 0.02465891

TPK1 thiamin pyrophosphokinase 1 2.044392 0.01332447

NUMBL numb homolog (Drosophila)-like 2.044282 0.02042735

TNF receptor-associated factor 3 interacting

TRAF3IP1 protein 1 2.041668 0.01902153 Y07B myosin VIIB 2.040729 0.03517199

ZNF280D zinc finger protein 280D 2.040638 0.01287239

GON4L gon-4-like (C. elegans) 2.039724 0.00904551

CARD6 caspase recruitment domain family, member 6 2.039599 0.03505956

PMPCB peptidase (mitochondrial processing) beta 2.037316 0.0072201

RAI14 retinoic acid induced 14 2.037265 0.01396032

MRPS2 Mitochondrial ribosomal protein S2 2.036969 0.01324621

PTGES prostaglandin E synthase 2.036575 0.03336

AHI1 Abelson helper integration site 1 2.035579 0.04434107

KPNA4 karyopherin alpha 4 (importin alpha 3) 2.033804 0.0449059

6-phosphofructo-2-kinase/fructose-2,6-

PFKFB2 biphosphatase 2 2.033696 0.01710018

MRPL9 mitochondrial ribosomal protein L9 2.03358 0.0281763

CD99 CD99 molecule 2.032985 0.02604604

SV2A synaptic vesicle glycoprotein 2A 2.032477 0.00939645

TNPOl transportin 1 2.032411 0.03457859

CLCN3 chloride channel 3 2.032305 0.03797608

SLC25A36 solute carrier family 25, member 36 2.031 104 0.01642812

FBXO30 F-box protein 30 2.030227 0.03710819

VARS valyl- RNA synthetase 2.029225 0.01223473 epidermal growth factor receptor pathway

EPS 8 substrate 8 2.029185 0.01334663 succinate-CoA ligase, ADP-forming, beta

SUCLA2 subunit 2.028111 0.02841861

LOC440258 similar to p40 2.027771 0.02833365

MOCO sulphurase C-terminal domain

MOSC2 containing 2 2.027181 0.00651 172

PPP4R2 Protein phosphatase 4, regulatory subunit 2 2.027077 0.02103272

CCNH cyclin H 2.023407 0.01901314

LARS Leucyl-tRNA synthetase 2.023019 0.04063478

ZNF680 zinc finger protein 680 2.020695 0.04882328

CCNT2 cyclin T2 2.020354 0.02162493

FBXL5 F-box and leucine-rich repeat protein 5 2.020009 0.02326966 family with sequence similarity 175, member

FAM175A A 2.019364 0.02563397

ANKRD28 ankyrin repeat domain 28 2.018849 0.01234883

Amyotrophic lateral sclerosis 2 (juvenile)

ALS2CR12 chromosome region, candidate 12 2.018779 0.0246608

DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P

Change value

MAGEA10 melanoma antigen family A, 10 2.017044 0.00170272 CXorf48 chromosome X open reading frame 48 2.015612 0.00266866 mitochondrial translational release factor 1-

MTRF1L like 2.015598 0.02725181

C18orfl0 chromosome 18 open reading frame 10 2.015562 0.03614906

ZIC4 Zic family member 4 2.014997 0.01917248

KLHL8 kelch-like 8 (Drosophila) 2.014654 0.01102863

MAP4 microtubule-associated protein 4 2.014438 0.02834198

C2orf34 chromosome 2 open reading frame 34 2.013589 0.01841428

ACTR2 ARP2 actin-related protein 2 homolog (yeast) 2.013524 0.01953361

TINP1 TGF beta-inducible nuclear protein 1 2.012733 0.01185654

RRM2 ribonucleotide reductase M2 2.012222 0.02429985

ZNF808 zinc finger protein 808 2.011438 0.01431641 eukaryotic translation initiation factor 4E

EIF4E3 family member 3 2.01088 0.00176835 solute carrier family 24

(sodium/potassium/ calcium exchanger),

SLC24A2 member 2 2.010115 0.00773363 solute carrier family 30 (zinc transporter),

SLC30A9 member 9 2.009116 0.04176149

TCF15 transcription factor 15 (basic helix-loop-helix) 2.008698 0.01765963

NBEAL1 neurobeachin-like 1 2.007726 0.0082173

DECR1 2,4-dienoyl Co A reductase 1, mitochondrial 2.006511 0.02598747

YIPF7 Yipl domain family, member 7 2.005932 0.03323522 guanine nucleotide binding protein-like 3

GNL3 (nucleolar) 2.005014 0.01735622

OMA1 homolog, zinc metallopeptidase (S.

OMA1 cerevisiae) 2.004871 0.02245231

PPHLN1 periphilin 1 2.004551 0.0049265

CLK1 CDC-like kinase 1 2.004524 0.04900386 capping protein (actin filament) muscle Z-

CAPZA1 line, alpha 1 2.003944 0.00987919

CANX calnexin 2.003539 0.03158557

SPTBN1 spectrin, beta, non-erythrocytic 1 2.003526 0.01072906

RIP 2 receptor-interacting serine-threonine kinase 2 2.003357 0.03042595

DIAPH1 diaphanous homolog 1 (Drosophila) 2.00281 0.01282001

ENSA endosulfme alpha 1.99941 1 0.03603591 regulatory factor X, 4 (influences HLA class

RFX4 II expression) 1.997391 0.03304527 MAPK9 mitogen-activated protein kinase 9 1.995129 0.01967538

Ras association (RalGDS/AF-6) domain

RASSF2 family member 2 1.993259 0.03641806

MFN2 mitofusin 2 1.992952 0.03221295

RCOR3 REST corepressor 3 1.992215 0.02218741 acidic (leucine-rich) nuclear phosphoprotein

ANP32C 32 family, member C 1.992162 0.00301849

GBA2 glucosidase, beta (bile acid) 2 1.991158 0.02064247

HOXA1 homeobox Al 1.989685 0.00084825 poly(A) binding protein, cytoplasmic 4

PABPC4 (inducible form) 1.988884 0.04115414

DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Up regulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

PALB2 partner and localizer of BRCA2 1.988632 8.7529E-05

ADAM metallopeptidase with

ADAMTS19 thrombospondin type 1 motif, 19 1.987229 0.04221038 FH fumarate hydratase 1.987209 0.01470817

PAX interacting (with transcription-activation

PAXIP1 domain) protein 1 1.987167 0.00945075 C4orf30 Chromosome 4 open reading frame 30 1.986477 0.03376819 MAP IB microtubule-associated protein IB 1.986421 0.04501 189 CYTL1 cytokine-like 1 1.986119 0.02339349 family with sequence similarity 36, member

FAM36A A 1.984139 0.01021283 EOMES eomesodermin homolog (Xenopus laevis) 1.983701 0.03056956

Asparagine-linked glycosylation 13 homolog

ALG13 (S. cerevisiae) 1.983324 0.01607156 SCYL2 SCYl -like 2 (S. cerevisiae) 1.982964 0.02371303 TGFB2 transforming growth factor, beta 2 1.98254 0.00552652 PTPRF protein tyrosine phosphatase, receptor type, F 1.98214 0.01266958 sine oculis binding protein homolog

SOBP (Drosophila) 1.981332 0.0455914

NRBP1 nuclear receptor binding protein 1 1.980841 0.02904591

VEGFC vascular endothelial growth factor C 1.980744 0.03038233

SLBP stem-loop binding protein 1.980568 0.02420595

ZNF703 zinc finger protein 703 1.980407 0.03514242

MAEL maelstrom homolog (Drosophila) 1.979551 0.01975137 zinc finger (CCCH type), RNA-binding motif

ZRSR2 and serine/arginine rich 2 1.979446 0.01662268 STAG3L1 stromal antigen 3 -like 1 1.978732 0.03091 125 bromodomain adjacent to zinc finger domain,

BAZ1A 1A 1.978716 0.04410899

JAZF1 JAZF zinc finger 1 1.9781 19 0.01784466

ITGB1BP1 integrin beta 1 binding protein 1 1.976987 0.01098471 cold shock domain containing El , RNA-

CSDE1 binding 1.976748 0.00578696 ZNF146 zinc finger protein 146 1.976382 0.0063506 required for meiotic nuclear division 1

PvMNDl homolog (S. cerevisiae) 1.976076 0.01276677 Cl lorf24 chromosome 11 open reading frame 24 1.976002 0.03708733 interleukin 6 signal transducer (gpl30,

IL6ST oncostatin M receptor) 1.974678 0.03531945

HMGB2 high-mobility group box 2 1.972844 0.03882638

WNK1 WNK lysine deficient protein kinase 1 1.972532 0.03135278

SYNE1 spectrin repeat containing, nuclear envelope 1 1.972468 0.02203298

ENOX2 ecto-NOX disulfide-thiol exchanger 2 1.972447 0.00185752

TRIO triple functional domain (PTPRF interacting) 1.971861 0.04525982

SNX25 sorting nexin 25 1.97084 0.02835255

PDCD6IP programmed cell death 6 interacting protein 1.970203 0.00643999 polycystic kidney and hepatic disease 1

P HD1 (autosomal recessive) 1.96957 0.04031886 RPAP2 RNA polymerase II associated protein 2 1.968633 0.04430806 FOXP4 forkhead box P4 1.96737 0.02497707

DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

CCDC106 coiled-coil domain containing 106 0.03760185 KIAA1244 KIAA1244 0.02415564 heterogeneous nuclear ribonucleoprotein L-

HNRPLL like 0.02133848 SMN1 survival of motor neuron 1 , telomeric 0.01301356 solute carrier family 22 (organic

SLC22A5 cation/carnitine transporter), member 5 1.964157 0.01562213

NADH dehydrogenase (ubiquinone) 1 alpha

NDUFA5 subcomplex, 5, 13kDa 0.0163378

ZFYVE16 zinc finger, FYVE domain containing 16 0.02898199

SCAMPI secretory carrier membrane protein 1 0.01389306

LSM3 homolog, U6 small nuclear RNA

LSM3 associated (S. cerevisiae) 0.040095

ZNF383 zinc finger protein 383 0.02949167

HDAC1 histone deacetylase 1 0.03332611 synaptotagmin binding, cytoplasmic RNA

SYNCRIP interacting protein 0.0125552

GLCCI1 glucocorticoid induced transcript 1 0.02892498

NARG1L NMD A receptor regulated 1-like 0.03712153

ACAT2 acetyl-CoA acetyltransferase 2 0.02631314

HEXB hexosaminidase B (beta polypeptide) 0.02870889

ZMAT3 zinc finger, matrin type 3 0.02830097

SRPKl SFRS protein kinase 1 0.040619 myeloid/lymphoid or mixed-lineage leukemia

(trithorax homolog, Drosophila); translocated

MLLT4 to, 4 0.02928524 EPS8L1 EPS8-like 1 0.02393049 phosphatidylinositol-4-phosphate 5-kinase,

PIP5K1A type I, alpha 0.02814202

RNF2 ring finger protein 2 0.00229371

MYT1L Myelin transcription factor 1-like 0.0270455

HSD17B13 N/A 0.0107758

FOXN2 forkhead box N2 0.00671655

ARL13B ADP-ribosylation factor-like 13B 0.02765269

OTOA otoancorin 0.03858649

DOCK 10 dedicator of cytokinesis 10 0.04532886 transmembrane anterior posterior

TAPT1 transformation 1 0.03685464

HERC2 hect domain and RLD 2 0.01772168

ZNF585A zinc finger protein 585A 0.01764023 ras-related C3 botulinum toxin substrate 3

RAC3 (rho family, small GTP binding protein Rac3) 0.01804715

PEX1 peroxisomal biogenesis factor 1 0.04410996

UBP1 upstream binding protein 1 (LBP-la) 0.02987965

CRTAP cartilage associated protein 0.02923402

SNX5 sorting nexin 5 0.00305077 ashl (absent, small, or homeotic)-like

ASH1L (Drosophila) 0.00682926 low density lipoprotein receptor-related

LRP10 protein 10 0.03200017 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value family with sequence similarity 168, member

FAM168B B 1.94061 0.01272885

CHN1 chimerin (chimaerin) 1 1.940576 0.04939486

Clorfl07 chromosome 1 open reading frame 107 1.940243 0.00831193

STMN3 stathmin-like 3 1.940169 0.00605162

GDI2 GDP dissociation inhibitor 2 1.939501 0.0168794

NCOR2 nuclear receptor co-repressor 2 1.938642 0.01865703 solute carrier family 13 (sodium/sulfate

SLC13A1 symporters), member 1 1.938483 0.03936365

SPATA5 Spermatogenesis associated 5 1.938449 0.01321604

APEX nuclease (multifunctional DNA repair

APEX1 enzyme) 1 1.937633 0.01208949

GSG1 germ cell associated 1 1.937607 0.00648467

CDK8 cyclin-dependent kinase 8 1.937355 0.03136558

ATP-binding cassette, sub-family E (OABP),

ABCE1 member 1 1.937131 0.02691982

NCBP2 nuclear cap binding protein subunit 2, 20kDa 1.937007 0.02064931

KIF14 kinesin family member 14 1.936247 0.0032016

EIF2C3 eukaryotic translation initiation factor 2C, 3 1.935179 0.01426257

METTL8 methyltransferase like 8 1.935148 0.02112268

GOLGA6 Golgi autoantigen, golgin subfamily a, 6 1.933403 0.04515888

ARHGAP10 Rho GTPase activating protein 10 1.93239 0.04924193

FANCL Fanconi anemia, complementation group L 1.931456 0.02324647

SH3 domain containing, Ysc84-like 1 (S.

SH3YL1 cerevisiae) 1.930488 0.00369118

CCND1 Cyclin Dl 1.930024 0.02353764

TMEM43 transmembrane protein 43 1.9291 1 0.03823184

ST 4 serine/threonine kinase 4 1.928017 0.04964894

BCAP29 B-cell receptor-associated protein 29 1.927448 0.02335138 protein phosphatase 3, regulatory subunit B,

PPP3R1 alpha 1.927241 0.00379102

ClOorfSl chromosome 10 open reading frame 81 1.926848 0.02650434

GUF1 GUF1 GTPase homolog (S. cerevisiae) 1.925977 0.00983607

FAM71B family with sequence similarity 71, member B 1.925723 0.03504079

FKSG2 apoptosis inhibitor pseudogene 1.925185 0.02233347

KIAA1715 KIAA1715 1.924517 0.00309567

HDLBP high density lipoprotein binding protein 1.923995 0.0317557

MARS2 methionyl-tRNA synthetase 2, mitochondrial 1.922729 0.0316077

CARKD carbohydrate kinase domain containing 1.922615 0.02370834

RIF1 RAP1 interacting factor homolog (yeast) 1.921728 0.00139196

ITSN1 intersectin 1 (SH3 domain protein) 1.920858 0.04228789

BLZF1 basic leucine zipper nuclear factor 1 1.920386 0.01207716

AKAP13 A kinase (PRKA) anchor protein 13 1.919293 0.0199231

MRPL30 Mitochondrial ribosomal protein L30 1.918716 0.03846072

PFKP phosphofructokinase, platelet 1.915717 0.03636159

TRIM46 tripartite motif-containing 46 1.915667 0.04531322

DLX6 Distal-less homeobox 6 1.915346 0.0157222

Clorf2 Chromosome 1 open reading frame 2 1.913413 0.03292338

CCDC14 coiled-coil domain containing 14 1.912883 0.03675871

C6orfl30 chromosome 6 open reading frame 130 1.912328 0.03702703 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

TRIM7 tripartite motif-containing 7 1.911771 0.04613831

Ctr9, Pafl/RNA polymerase II complex

CTR9 component, homolog (S. cerevisiae) 1.91141 1 0.00146435 mesoderm induction early response 1 , family

MIER3 member 3 1.911318 0.03539947

CDCA7 cell division cycle associated 7 1.909849 0.02148121 general transcription factor IIIC, polypeptide

GTF3C3 3, 102kDa 1.909257 0.02969776

SH3 domain binding glutamic acid-rich

SH3BGRL2 protein like 2 1.908088 0.04631696

MARK3 MAP/microtubule affinity-regulating kinase 3 1.907991 0.02768508 retinal pigment epithelium-specific protein

RPE65 65kDa 1.907053 0.03622687

TCDD-inducible poly(ADP-ribose)

TIPARP polymerase 1.905094 0.00574133

ZFC3H1 zinc finger, C3 HI -type containing 1.900462 0.02823067

EPB41L2 erythrocyte membrane protein band 4.1 -like 2 1.900297 0.01730491

OAZ1 ornithine decarboxylase antizyme 1 1.900225 0.02095961

C6orf72 chromosome 6 open reading frame 72 1.897897 0.02078785 coatomer protein complex, subunit beta 2

COPB2 (beta prime) 1.897638 0.00131933

NUB1 negative regulator of ubiquitin-like proteins 1 1.897502 0.02103466 fatty acid desaturase domain family, member

FADS 6 6 1.894571 0.03555164

RINT1 RAD50 interactor 1 1.893722 0.04722573

MGC72080 MGC72080 pseudogene 1.892463 0.03778642 signal transducer and activator of

STAT6 transcription 6, interleukin-4 induced 1.892197 0.02746931 solute carrier family 30 (zinc transporter),

SLC30A6 member 6 1.891436 0.04633887

UBA5 ubiquitin-like modifier activating enzyme 5 1.891374 0.00330857

ATPase, Na+/K+ transporting, beta 3

ATP1B3 polypeptide 1.889678 0.03406585

SCFD2 seel family domain containing 2 1.888964 0.04069324

STX7 syntaxin 7 1.888885 0.02528416

NCOA7 nuclear receptor coactivator 7 1.888606 0.03681894

ATP-binding cassette, sub-family B

ABCB10 (MDR/TAP), member 10 1.888537 0.03715891

NBR1 neighbor of BRCAl gene 1 1.888532 0.01926365

C16orf89 chromosome 16 open reading frame 89 1.887752 0.03611261

COPA coatomer protein complex, subunit alpha 1.887729 0.00523307

C5orf30 chromosome 5 open reading frame 30 1.887009 0.04109688

BRD2 bromodomain containing 2 1.886865 0.02782694

CSF1R colony stimulating factor 1 receptor 1.886363 0.02272235

VPS13B vacuolar protein sorting 13 homolog B (yeast) 1.883804 0.02306275

EVI5 ecotropic viral integration site 5 1.883555 0.02040397

SLC35A4 solute carrier family 35, member A4 1.882568 0.0078888

PUM1 pumilio homolog 1 (Drosophila) 1.882087 0.0152859

CCDC50 coiled-coil domain containing 50 1.88064 0.01476253

CNOT4 CCR4-NOT transcription complex, subunit 4 1.880325 0.03303252

⁾B 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P

Change value

DEAH (Asp-Glu-Ala-His) box polypeptide

DHX16 16 1.878271 0.03067186 proteasome (prosome, macropain) subunit,

PSMB1 beta type, 1 1.877973 0.0332617

R ASEH1 ribonuclease HI 1.877097 0.04098147

SCAPER S-phase cyclin A-associated protein in the ER 1.877076 0.03100614

CD47 CD47 molecule 1.87569 0.01888597 small nucleolar RNA host gene 3 (non-protein

SNHG3 coding) 1.874207 0.03386067 cytochrome c oxidase subunit Vila

COX7A2L polypeptide 2 like 1.873646 0.01067705

OCLM oculomedin 1.87256 0.01814809

TAPBP TAP binding protein (tapasin) 1.872215 0.00473798

DnaJ (Hsp40) homolog, subfamily A,

DNAJA2 member 2 1.871391 0.04124373 integrin, alpha 3 (antigen CD49C, alpha 3

ITGA3 subunit of VLA-3 receptor) 1.870354 0.01607103

ZFP62 Zinc finger protein 62 homolog (mouse) 1.870152 0.0367302 centrosome and spindle pole associated

CSPP1 protein 1 1.870004 0.01855885

ATP synthase, H+ transporting, mitochondrial

ATP5I F0 complex, subunit E 1.869679 0.04573862

RUFY3 RUN and FYVE domain containing 3 1.86885 0.02251787

CAPN2 calpain 2, (m/II) large subunit 1.868506 0.02067163

MAL2 mal, T-cell differentiation protein 2 1.868321 0.03505472

NCK1 NCK adaptor protein 1 1.868271 0.04033407

FBXL6 F-box and leucine-rich repeat protein 6 1.86584 0.00455271

NBPF3 neuroblastoma breakpoint family, member 3 1.865622 0.01157426

YY1 YY1 transcription factor 1.865234 0.03212851 glutamine~fructose-6-phosphate transaminase

GFPT1 1 1.865212 0.0396156 telomeric repeat binding factor (NIMA-

TERF1 interacting) 1 1.863569 0.01246509

RYR2 ryanodine receptor 2 (cardiac) 1.862881 0.00676912

SERTAD2 SERTA domain containing 2 1.862785 0.04590001

DNA fragmentation factor, 45kDa, alpha

DFFA polypeptide 1.862478 0.00013042

CS D1 CUB and Sushi multiple domains 1 1.862332 0.04201276 vacuolar protein sorting 54 homolog (S.

VPS54 cerevisiae) 1.861531 0.02581 185

BHLHE40 basic helix-loop-helix family, member e40 1.861054 0.03922092

TXLNA taxilin alpha 1.860106 0.01027444 transcription termination factor, RNA

TTF2 polymerase II 1.860101 0.01263657

ZNF675 zinc finger protein 675 1.859548 0.02027401

TPD52L1 tumor protein D52-like 1 1.85881 0.02469977

WDR1 WD repeat domain 1 1.858527 0.02723528

ADAM 17 ADAM metallopeptidase domain 17 1.85588 0.03368281

ZMYM1 zinc finger, MYM-type 1 1.855192 0.02837831

SRP14 signal recognition particle 14kDa 1.854744 0.04366461

DB1/ 69 37516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

(homologous Alu RNA binding protein)

Cell division cycle 2-like 5 (cholinesterase-

CDC2L5 related cell division controller) 1.851878 0.03689202

TCTEX1D2 Tcte l domain containing 2 1.851061 0.02861069 mitogen-activated protein kinase associated

MAPKAP1 protein 1 1.850653 0.00888942

CAP-GLY domain containing linker protein

CLIP4 family, member 4 1.850067 0.02074231

GNPDA1 glucosamine-6-phosphate deaminase 1 1.850039 0.01637317

TUBA1C tubulin, alpha 1 c 1.849291 0.00660798

ITIH5 inter-alpha (globulin) inhibitor H5 1.848427 0.03200304

GPX6 Glutathione peroxidase 6 (olfactory) 1.847981 0.00687069

OSBPL8 oxysterol binding protein-like 8 1.847204 0.02216573

USP37 ubiquitin specific peptidase 37 1.846954 0.01682321

RP5-

1000E10.4 N/A 1.846929 0.04792123

CUL9 cullin 9 1.846152 0.00918915

ZKSCAN1 zinc finger with KRAB and SCAN domains 1 1.846012 0.04781497

AGK acylglycerol kinase 1.845718 0.03987334

C5orf41 chromosome 5 open reading frame 41 1.844324 0.02521398

RPS8 ribosomal protein S8 1.843008 0.01108712

DZIP1 DAZ interacting protein 1 1.842491 0.02740508

IRX6 iroquois homeobox 6 1.841361 0.01970989

SFRS4 splicing factor, arginine/serine-rich 4 1.84064 0.04202668 mitogen-activated protein kinase kinase

MAP3K2 kinase 2 1.840608 0.02704039 sulfotransferase family, cytosolic, 2B,

SULT2B1 member 1 1.840301 0.00982224

ANKRD13B ankyrin repeat domain 13B 1.839917 0.00584462

10-Sep N/A 1.839698 0.03271688

HSPC159 galectin-related protein 1.838673 0.04609221

Transcriptional adaptor 1 (HFI1 homolog,

TADA1L yeast)-like 1.837958 0.04364506

CEP97 centrosomal protein 97kDa 1.836937 0.03083775

SRFBP1 serum response factor binding protein 1 1.836767 0.02852658 protein-kinase, interferon-inducible double

stranded RNA dependent inhibitor, repressor

PRKRIR of (P58 repressor) 1.836748 0.03060855 proteasome (prosome, macropain) 26S

PSMC1 subunit, ATPase, 1 1.83611 0.03905445

COL1A1 collagen, type I, alpha 1 1.835332 0.01491401

POLM polymerase (DNA directed), mu 1.834316 0.00459207

JAG1 Jagged 1 (Alagille syndrome) 1.834226 0.04605491

FHOD1 formin homology 2 domain containing 1 1.834128 0.03048125 family with sequence similarity 179, member

FAM179B B 1.834068 0.01655335

GYG1 glycogenin 1 1.833606 0.0066626

MANEA mannosidase, endo-alpha 1.833248 0.00915157 transcription factor 3 (E2A immunoglobulin

TCF3 enhancer binding factors E12/E47) 1.832816 0.02904369

⁾B1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

CRLF3 cytokine receptor-like factor 3 1.832458 0.00595834

LASP1 LIM and SH3 protein 1 1.83209 0.01310591

ATG5 autophagy related 5 homolog (S.

ATG5 cerevisiae) 1.832006 0.02084733

CEP70 centrosomal protein 70kDa 1.829564 0.02190007

CAST calpastatin 1.82713 0.036828

BBX bobby sox homolog (Drosophila) 1.826748 0.04610618

IP09 importin 9 1.82644 0.00165259

TXNDC15 thioredoxin domain containing 15 1.825123 0.04375771 intraflagellar transport 122 homolog

IFT122 (Chlamydomonas) 1.825087 0.00170948

YAP1 Yes-associated protein 1 1.824953 0.04116296

MYLK myosin light chain kinase 1.82455 0.00267066 solute carrier family 17 (anion/sugar

SLC17A5 transporter), member 5 1.823754 0.01905067 synovial sarcoma, X breakpoint 2 interacting

SSX2IP protein 1.823722 0.03458225

MRPL10 Mitochondrial ribosomal protein L10 1.823153 0.03948173

TUB tubby homolog (mouse) 1.821968 0.02603894

HIPK2 Homeodomain interacting protein kinase 2 1.821826 0.04983625

RCVR recoverin 1.820797 0.02437665

KIF3A kinesin family member 3 A 1.818053 0.01799915 erythrocyte membrane protein band 4.1

EPB41 (elliptocytosis 1, RH-linked) 1.817829 0.022056

TIA1 cytotoxic granule-associated R A

TIA1 binding protein 1.817796 0.02926846

CDC23 Cell division cycle 23 homolog (S. cerevisiae) 1.817618 0.03921417

SAT1 spermidine/spermine Nl-acetyltransferase 1 1.817253 0.01695831 microtubule associated monoxygenase,

MICAL2 calponin and LIM domain containing 2 1.817247 0.0077313

C4or£21 chromosome 4 open reading frame 21 1.816677 0.04909137 purinergic receptor P2X, ligand-gated ion

P2RX1 channel, 1 1.816601 0.00616274

C5orf43 chromosome 5 open reading frame 43 1.81604 0.01543196 proteasome (prosome, macropain) subunit,

PSMA7 alpha type, 7 1.814899 0.0228106

C17orf5 chromosome 17 open reading frame 57 1.814854 0.03520185

NADH dehydrogenase (ubiquinone) 1,

NDUFC1 subcomplex unknown, 1, 6kDa 1.814744 0.00472754 serine/threonine kinase 25 (STE20 homolog,

STK25 yeast) 1.813528 0.02207752

Rho guanine nucleotide exchange factor

ARHGEF11 (GEF) 11 1.812046 0.03352064

PK 2 protein kinase N2 1.81078 0.03572897 polymerase (RNA) II (DNA directed)

POLR2J4 polypeptide J4, pseudogene 1.810565 0.03929667 blocked early in transport 1 homolog (S.

BET1 cerevisiae) 1.810406 0.04306222

RIOK3 RIO kinase 3 (yeast) 1.810224 0.04030526

ATP5B ATP synthase, H+ transporting, mitochondrial 1.809531 0.04418697

DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Chan value

Fl complex, beta polypeptide

ARCN1 archain 1 1.808802 0.02287658 RPL23AP7 ribosomal protein L23a pseudogene 7 1.808578 0.01058161

Rho guanine nucleotide exchange factor

ARHGEF10 (GEF) 10 1.807515 0.02547119 STXBP6 syntaxin binding protein 6 (amisyn) 1.807136 0.04173158 protein tyrosine phosphatase, non-receptor

PTPN9 type 9 1.806452 0.03400917 C6orfl50 chromosome 6 open reading frame 150 1.805382 0.00837178 excision repair cross-complementing rodent

repair deficiency, complementation group 3

(xeroderma pigmentosum group B

ERCC3 complementing) 1.80534 0.03842784 Clorf9 Chromosome 1 open reading frame 9 1.804845 0.0210386 asp (abnormal spindle) homolog,

ASPM microcephaly associated (Drosophila) 1.803894 0.04304251 EDAR ectodysplasin A receptor 1.802901 0.0484354 HECA headcase homolog (Drosophila) 1.80288 0.02267831 roundabout, axon guidance receptor, homolog

ROBOl I (Drosophila) 1.802834 0.03733771

KIAA0907 KIAA0907 1.802135 0.01635821

CADM1 cell adhesion molecule 1 1.801595 0.01731324

EIF2C1 eukaryotic translation initiation factor 2C, 1 1.801198 0.02584671

ATXN1 ataxin 1 1.800174 0.04856069

BMX BMX non-receptor tyrosine kinase 1.799917 0.0132007

THUMPD3 THUMP domain containing 3 1.798321 0.02891873 TNNI3K TN I3 interacting kinase 1.796699 0.00422282

DnaJ (Hsp40) homolog, subfamily C, member

DNAJC7 7 1.79528 0.04547126 solute carrier family 1 (glutamate/neutral

SLC1A4 amino acid transporter), member 4 1.794159 0.0013034 PREPL prolyl endopeptidase-like 1.793794 0.02865172 protein O-linked mannose betal,2-N-

POMGNT1 acetylglucosaminyltransferase 1.793763 0.00419277 BBS7 Bardet-Biedl syndrome 7 1.793614 0.0295155 calcium/calmodulin-dependent protein kinase

CAMK2A II alpha 1.79334 0.01140048

DnaJ (Hsp40) homolog, subfamily C, member

DNAJC11 11 1.792024 0.01033343 solute carrier organic anion transporter

SLC03A1 family, member 3A1 1.789337 0.02548138

HNRNPAO heterogeneous nuclear ribonucleoprotein AO 1.789162 0.0369539

NRCAM neuronal cell adhesion molecule 1.788258 0.02131313 family with sequence similarity 128, member

FAM128A A 1.787413 0.00608961 STAG3L4 stromal antigen 3 -like 4 1.787315 0.04479751 succinate-CoA ligase, GDP-forming, beta

SUCLG2 subunit 1.786827 0.00924396

UBXN7 UBX domain protein 7 1.786441 0.0022891

RABGAP1L RAB GTPase activating protein 1 -like 1.785973 0.01839424

DBl/ 09437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

LMNB1 lamin Bl 1.785446 0.02155216

FIG4 homolog, SAC1 lipid phosphatase

FIG4 domain containing (S. cerevisiae) 1.784998 0.01721844 LASS2 LAG1 homolog, ceramide synthase 2 1.783932 0.01893847 programmed cell death 4 (neoplastic

PDCD4 transformation inhibitor) 1.78353 0.02762895

SAP30 Sin3A-associated protein, 30kDa 1.783367 0.04714102

ZBTB10 zinc finger and BTB domain containing 10 1.783247 0.01564548

CCDC76 coiled-coil domain containing 76 1.78322 0.01357722

NOS2 nitric oxide synthase 2, inducible 1.783161 0.01310977

FBXW7 F-box and WD repeat domain containing 7 1.782983 0.0196405

T IM52 tripartite motif-containing 52 1.782673 0.0424533

SUZ12 suppressor of zeste 12 homolog (Drosophila) 1.781738 0.0427054

SH3GLB2 SH3 -domain GRB2-like endophilin B2 1.77951 0.02756375

SCAND3 SCAN domain containing 3 1.779181 0.04344292

MCM3AP antisense RNA (non-protein

MCM3APAS coding) 1.777941 0.02758222

WTAP Wilms tumor 1 associated protein 1.777876 0.00868387

ZNF354C zinc finger protein 354C 1.777855 0.0062276

CASP8AP2 caspase 8 associated protein 2 1.77773 0.00912374

CRHR2 corticotropin releasing hormone receptor 2 1.776097 0.00279438

TTRAP TRAF and TNF receptor associated protein 1.775492 0.04327018

AFF3 AF4/FMR2 family, member 3 1.774709 0.04961151 acidic (leucine-rich) nuclear phosphoprotein

ANP32A 32 family, member A 1.773795 0.00540646

AKAP8 A kinase (PRKA) anchor protein 8 1.773053 0.00229454

PBRM1 polybromo 1 1.771167 0.03425846

PM20D1 peptidase M20 domain containing 1 1.770845 0.02670605

IFIH1 interferon induced with helicase C domain 1 1.770252 0.04974546

ICA1 islet cell autoantigen 1, 69kDa 1.770105 0.03019432

AGBL5 ATP/GTP binding protein-like 5 1.770017 0.04332805

NAV3 neuron navigator 3 1.770005 0.04660366

LYG2 lysozyme G-like 2 1.769802 0.01444479

DDR1 discoidin domain receptor tyrosine kinase 1 1.769628 0.02493444

Z F213 zinc finger protein 213 1.76888 0.02160061

ArfGAP with GTPase domain, ankyrin repeat

AGAP2 and PH domain 2 1.768822 0.03622317 GOLPH3 golgi phosphoprotein 3 (coat-protein) 1.768741 0.03226337 down-regulator of transcription 1 , TBP-

DR1 binding (negative cofactor 2) 1.767005 0.02631065 TNXB tenascin XB 1.766861 0.02330234

TAF8 RNA polymerase II, TATA box

binding protein (TBP)-associated factor,

TAF8 43kDa 1.766752 0.04249763

WDR26 WD repeat domain 26 1.766404 0.04389929

DHCR24 24-dehydrocholesterol reductase 1.766311 0.03658698

COQ9 coenzyme Q9 homolog (S. cerevisiae) 1.763676 0.02397798

STXBP4 Syntaxin binding protein 4 1.762673 0.02317395

CTSL1 cathepsin LI 1.762195 0.00671078

ZMYND11 zinc finger, MY D domain containing 11 1.762069 0.04523794

DB l/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

CRISP3 cysteine-rich secretory protein 3 1.761506 0.03613203

FUR Fl 1 receptor 1.761288 0.02412146

Sema domain, immunoglobulin domain (Ig),

transmembrane domain (TM) and short

SEMA4A cytoplasmic domain, (semaphorin) 4A 1.760637 0.00035897

MAM domain containing

MDGA1 glycosylphosphatidylinositol anchor 1 1.760367 0.03598768 protein phosphatase 1 , regulatory (inhibitor)

PPP1R13L subunit 13 like 1.7592 0.04452406

SMYD5 SMYD family member 5 1.758334 0.03952075

SFRS15 splicing factor, arginine/serine-rich 15 1.758154 0.0470158

BAI1 brain-specific angiogenesis inhibitor 1 1.756649 0.00916272 v-erb-b2 erythroblastic leukemia viral

oncogene homolog 2, neuro/glioblastoma

ERBB2 derived oncogene homolog (avian) 1.755689 0.02545648

Clorfl68 chromosome 1 open reading frame 168 1.755419 0.03359442

LHFPL4 Lipoma HMGIC fusion partner-like 4 1.754908 0.00212537

RNF5P1 ring finger protein 5 pseudogene 1 1.754173 0.02376122 protein-L-isoaspartate (D-aspartate) 0-

PCMT1 methyltransferase 1.753126 0.01819688

RYK RYK receptor-like tyrosine kinase 1.751194 0.00185441 adaptor-related protein complex 2, alpha 2

AP2A2 subunit 1.751007 0.01495759

ATP11B ATPase, class VI, type 1 IB 1.750681 0.0249001 1

CNOT8 CCR4-NOT transcription complex, subunit 8 1.750479 0.04298721 eukaryotic translation initiation factor 4

EIF4G1 gamma, 1 1.750254 0.00740522

HOXA13 homeobox A13 1.748129 0.03914432

MRAS muscle RAS oncogene homolog 1.747667 0.0018277

Methylcrotonoyl-Coenzyme A carboxylase 1

MCCC1 (alpha) 1.746294 0.0228626

CD74 molecule, major histocompatibility

CD74 complex, class II invariant chain 1.744558 0.0075195 mitogen-activated protein kinase kinase

MAP3K7 kinase 7 1.743976 0.02238046

C9orfl40 chromosome 9 open reading frame 140 1.742816 0.03971348

ZNF654 zinc finger protein 654 1.742812 0.01596965 small nuclear ribonucleoprotein polypeptide

SNRPC C 1.742362 0.04469681

TSGA10 testis specific, 10 1.741521 0.02049649

PRDM2 PR domain containing 2, with ZNF domain 1.740844 0.04930196

SDAD1 SDA1 domain containing 1 1.740613 0.02810075

ZNF 10 zinc finger protein 510 1.73974 0.00011319

ZFYVE28 zinc finger, FYVE domain containing 28 1.739287 0.01571989

NFE2L3 nuclear factor (erythroid-derived 2)-like 3 1.738235 0.01922635

ZNF384 zinc finger protein 384 1.737747 0.03729418

GNAS GNAS complex locus 1.736578 0.0214594

TUBB4 tubulin, beta 4 1.736534 0.00359016

SFRS12IP1 SFRS12-interacting protein 1 1.736013 0.00899882

PLK2 polo-like kinase 2 (Drosophila) 1.735402 0.03172869

)B 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

HSPA4L heat shock 70kDa protein 4-like 1.733956 0.04720531 NKAP NFKB activating protein 1.732831 0.02649561

DEAD/H (Asp-Glu-Ala-Asp/His) box

polypeptide 11 (CHL 1 -like helicase homolog,

DDX1 1 S. cerevisiae) 1.732086 0.00580239

DnaJ (Hsp40) homolog, subfamily B, member

DNAJB8 8 1.731683 0.03375359

ZC3H8 zinc finger CCCH-type containing 8 1.731254 0.03446465

DZIP3 DAZ interacting protein 3, zinc finger 1.73111 1 0.02789567 integrin, alpha 2 (CD49B, alpha 2 subunit of

ITGA2 VLA-2 receptor) 1.731067 0.03490653 KIAA0528 KIAA0528 1.730924 0.0064972 solute carrier family 2 (facilitated glucose

SLC2A1 transporter), member 1 1.730841 0.01057146 LGALS8 lectin, galactoside-binding, soluble, 8 1.73016 0.02373729 serine threonine kinase 39 (STE20/SPS1

STK39 homolog, yeast) 1.729703 0.04202932 TMEM120A transmembrane protein 120A 1.729431 0.04351484 CEP 164 centrosomal protein 164kDa 1.728991 0.01830317 DARS aspartyl-tRNA synthetase 1.728775 0.03291067 phosphoinositide-3-kinase, catalytic, alpha

PIK3CA polypeptide 1.728352 0.03384356 family with sequence similarity 8, member

FAM8A1 Al 1.727897 0.01676628

LIM and senescent cell antigen-like domains

LIMS1 1 1.72779 0.04472927 RPE ribulose-5 -phosphate-3 -epimerase 1.72725 0.04901899

BRMSIL breast cancer metastasis-suppressor 1 -like 1.726914 0.03549736 mitochondrial translation optimization 1

MTOl homolog (S. cerevisiae) 1.726686 0.03214024 CROT carnitine O-octanoyltransferase 1.726263 0.02848848 LEF1 Lymphoid enhancer-binding factor 1 1.725065 0.04118395 FIGNL1 fidgetin-like 1 1.724436 0.04113886 MTMR11 myotubularin related protein 11 1.724433 0.00608173 nudix (nucleoside diphosphate linked moiety

NUDT12 X)-type motif 12 1.724119 0.01468459

PTEN phosphatase and tensin homolog 1.723703 0.03642467

LMBRD1 LMBR1 domain containing 1 1.722225 0.00672219

CCDC138 coiled-coil domain containing 138 1.72192 0.01981292

TSPYL4 TSPY-like 4 1.721806 0.04163103 tankyrase, TRF1 -interacting ankyrin-related

TNKS ADP-ribose polymerase 1.721619 0.01032826 heterogeneous nuclear ribonucleoprotein C

HNRNPC (C1/C2) 1.721289 0.04511126 PLA2G3 phospholipase A2, group III 1.720314 0.01001067 calcium channel, voltage-dependent, L type,

CACNA1C alpha 1C subunit 1.720015 0.00384218 TULP3 tubby like protein 3 1.719888 0.00181719 LMBR1 limb region 1 homolog (mouse) 1.719877 0.02991854 TGFBRAP1 transforming growth factor, beta receptor 1.718545 0.00485692

DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value associated protein 1

patatin-like phospholipase domain containing

PNPLA8 8 1.717105 2.38E-06

C2orf29 chromosome 2 open reading frame 29 1.717065 0.01919981

C18orf21 chromosome 18 open reading frame 21 1.716032 0.02987306

SERBP1 SERPINE1 mRNA binding protein 1 1.715694 0.01072272

PEX3 peroxisomal biogenesis factor 3 1.714742 0.02148205 echinoderm microtubule associated protein

EML4 like 4 1.7145 0.02241195

SORBS2 sorbin and SH3 domain containing 2 1.714498 0.0455495

PTER phosphotriesterase related 1.714416 0.01735673

HDAC2 histone deacetylase 2 1.713956 0.04708192

CENPQ centromere protein Q 1.71339 0.0213132 family with sequence similarity 76, member

FAM76A A 1.712509 0.0157301

AIM2 absent in melanoma 2 1.71178 0.00998366

HOOK1 hook homolog 1 (Drosophila) 1.710771 0.02600011

ATP -binding cassette, sub-family B

ABCB8 (MDR/TAP), member 8 1.710166 0.00861395

CDC40 cell division cycle 40 homolog (S. cerevisiae) 1.709933 0.025953

SLC2A4RG SLC2A4 regulator 1.709081 0.04190288

C7orf38 Chromosome 7 open reading frame 38 1.708807 0.02303838

EPHA3 EPH receptor A3 1.708107 0.02252368

ALS2 Amyotrophic lateral sclerosis 2 (juvenile) 1.707659 0.00694015

FANCC Fanconi anemia, complementation group C 1.707104 0.02702837

CFLAR CASP8 and FADD-like apoptosis regulator 1.706199 0.02074358

MED30 mediator complex subunit 30 1.705178 0.01884414 family with sequence similarity 160, member

FAM160A2 A2 1.704982 0.03334977 catenin (cadherin-associated protein), alpha¬

CTNNAL1 like 1 1.704478 0.03948794

KLHL32 kelch-like 32 (Drosophila) 1.704126 0.03211128

G AP1 G kinase anchoring protein 1 1.704021 0.01022421 gamma-aminobutyric acid (GABA) A

GABRG2 receptor, gamma 2 1.703807 0.04593652

ALMS1 Alstrom syndrome 1 1.70361 0.04786654

ZNF189 zinc finger protein 189 1.702987 0.04710515

NRD1 nardilysin (N-arginine dibasic convertase) 1.702908 0.04096405

TMEM65 transmembrane protein 65 1.702792 0.02059544

Clorf27 chromosome 1 open reading frame 27 1.702394 0.02061163 general transcription factor HE, polypeptide 1,

GTF2E1 alpha 56kDa 1.702074 0.04249274

NOLC1 nucleolar and coiled-body phosphoprotein 1 1.70141 0.04459261

PINK1 PTEN induced putative kinase 1 1.701369 0.02986638

AGFG1 ArfGAP with FG repeats 1 1.700814 0.02888252

LHX8 LIM homeobox 8 1.698942 0.00318506 leucine zipper-EF-hand containing

LETM1 transmembrane protein 1 1.698753 0.02155205

NIT2 nitrilase family, member 2 1.697659 0.03895012

RNF130 ring finger protein 130 1.697257 0.01 112673

)B 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

ZNF286A zinc finger protein 286A 1.69708 0.00059534

RABGAP1 RAB GTPase activating protein 1 1.696465 0.02235212

Src homology 2 domain containing

SHD transforming protein D 1.696106 0.03305113

CD68 CD68 molecule 1.695795 0.00184294

WDR7 WD repeat domain 7 1.694536 0.02634425

JAK1 Janus kinase 1 1.69388 0.01522807

TRIM24 tripartite motif-containing 24 1.693411 0.04105101

Transient receptor potential cation channel,

TRPV3 subfamily V, member 3 1.693271 0.01071292 protein phosphatase 1 , regulatory (inhibitor)

PPP1R2 subunit 2 1.693178 0.00191476 staufen, RNA binding protein, homolog 1

STAU1 (Drosophila) 1.693099 0.04965607

PLD3 phospholipase D family, member 3 1.6923 0.04747022

COL5A1 collagen, type V, alpha 1 1.69213 0.04039646

SCD stearoyl-CoA desaturase (delta-9-desaturase) 1.692073 0.02710143

PLXND1 Plexin Dl 1.691717 0.02853845

CPNE3 copine III 1.691682 0.00274705 membrane associated guanylate kinase, WW

MAGI1 and PDZ domain containing 1 1.691656 0.03053273

MAPK3 mitogen-activated protein kinase 3 1.691005 0.04026195

UVRAG UV radiation resistance associated gene 1.690489 0.03919053

TEX 19 testis expressed 19 1.689462 0.02512695

C8orf33 chromosome 8 open reading frame 33 1.689323 0.0139295

DOPEY2 dopey family member 2 1.68908 0.04094941

DAP death-associated protein 1.688477 0.00441882

WASL Wiskott-Aldrich syndrome-like 1.688132 0.01807076

SAMD4A sterile alpha motif domain containing 4A 1.687902 0.005081 13

DIRC2 disrupted in renal carcinoma 2 1.686764 0.0406976

CDC5L CDC5 cell division cycle 5-like (S. pombe) 1.686596 0.00513394

XRN1 5 -3' exoribonuclease 1 1.685701 0.0437345

SECISBP2 SECIS binding protein 2 1.685434 0.0132207

DnaJ (Hsp40) homolog, subfamily B, member

DNAJB6 6 1.68511 0.02203927

COL4A5 collagen, type IV, alpha 5 1.684698 0.0014245 ubiquitin-conjugating enzyme E2H (UBC8

UBE2H homolog, yeast) 1.683991 0.00580532

HMBOX1 homeobox containing 1 1.682653 0.01652019

WDR3 WD repeat domain 3 1.682566 0.01179129

MYOM3 myomesin family, member 3 1.682278 0.01208733

Transcription factor 7-like 1 (T-cell specific,

TCF7L1 HMG-box) 1.682274 0.00738236 catenin (cadherin-associated protein), beta 1,

CTNNB1 88kDa 1.68156 0.01788189

TYMP thymidine phosphorylase 1.681529 0.04153714

NOSIP nitric oxide synthase interacting protein 1.681421 0.04395

EYA3 eyes absent homolog 3 (Drosophila) 1.681292 0.02095053

SLMAP sarcolemma associated protein 1.681183 0.044105

GGA2 golgi-associated, gamma adaptin ear 1.679827 0.00751514

B 1/ 69437516.1 Supplemental Tabic 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value containing, ARF binding protein 2

LAMP3 lysosomal-associated membrane protein 3 1.678861 0.02458607

RPL9 ribosomal protein L9 1.678778 0.02683837

TRIT1 tRNA isopenteny transferase 1 1.677877 0.04083159 protein kinase C and casein kinase substrate

PACSIN1 in neurons 1 1.676679 0.02027534 SP4 Sp4 transcription factor 1.676382 0.0490481 ribosome binding protein 1 homolog 180kDa

RRBP1 (dog) 1.676273 0.03208152 C3orf24 chromosome 3 open reading frame 24 1.676037 0.03229523 TMEM77 Transmembrane protein 77 1.675743 0.01021385 OCIAD1 OCIA domain containing 1 1.675522 0.0099691 tRNA splicing endonuclease 2 homolog (S.

TSEN2 cerevisiae) 1.675438 0.02583301

NSL1, MIND kinetochore complex

NSL1 component, homolog (S. cerevisiae) 1.675294 0.00175439

ZNF23 zinc finger protein 23 (KOX 16) 1.67496 0.03514622

ZNF302 zinc finger protein 302 1.674077 0.0485076

VTA1 Vps20-associated 1 homolog (S. cerevisiae) 1.673359 0.03794161

SLU7 SLU7 splicing factor homolog (S. cerevisiae) 1.673319 0.04457199

RPL27A ribosomal protein L27a 1.673236 0.01515691 CNK16 potassium channel, subfamily K, member 16 1.672001 0.02875484 adaptor-related protein complex 2, alpha 1

AP2A1 subunit 1.671987 0.03794131 RGPD2 RANBP2-like and GRIP domain containing 2 1.671712 0.01608914 RPL15 ribosomal protein LI 5 1.671399 0.00413895 NAIP NLR family, apoptosis inhibitory protein 1.67134 0.01945006 calcium/calmodulin-dependent protein kinase

CAMK2D II delta 1.671216 0.00929113

KIAA1012 KIAA1012 1.671 1 0.0435802

HOOK3 hook homolog 3 (Drosophila) 1.670954 0.03532757

BAI2 brain-specific angiogenesis inhibitor 2 1.670904 0.04007991

BEND7 BEN domain containing 7 1.67085 0.00838852

JUN jun oncogene 1.670629 0.00804181 eukaryotic translation initiation factor 3,

EIF3K subunit K 1.669436 0.00274533

WWC3 WWC family member 3 1.667972 0.01632484

ACOX1 Acyl-Coenzyme A oxidase 1, palmitoyl 1.667647 0.00796185 enhancer of polycomb homolog 1

EPC1 (Drosophila) 1.666674 0.01145716

PAIP1 poly(A) binding protein interacting protein 1 1.66649 0.03104414

CDK5RAP2 CDK5 regulatory subunit associated protein 2 1.665978 0.02623349

LPCAT2 lysophosphatidylcholine acyltransferase 2 1.665875 0.03018121

CYB5R4 cytochrome b5 reductase 4 1.665456 0.00509119

PKP2 plakophilin 2 1.665271 0.0236316

ADAMTSL4 ADAMTS-like 4 1.663953 0.03234697

CNOT6 CCR4-NOT transcription complex, subunit 6 1.663682 0.01038354

REV1 REV1 homolog (S. cerevisiae) 1.663518 0.03153223 chaperonin containing TCP1, subunit 3

CCT3 (gamma) 1.663267 0.04685597

DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

TBC1D17 TBC1 domain family, member 17 1.66246 0.02023361

LRRC1 Leucine rich repeat containing 1 1.66149 0.01283386

OSBPL6 oxysterol binding protein-like 6 1.661319 0.02184632

CLOCK clock homolog (mouse) 1.660451 0.0374842 recombination activating gene 1 activating

RAG1AP1 protein 1 1.660269 0.04756292

PHF15 PHD finger protein 15 1.660195 0.00139822

GORAB golgin, RAB6-interacting 1.660106 0.00607479 hCG 1817306 N/A 1.659972 0.03901822

ERGIC2 ERGIC and golgi 2 1.659425 0.0356255

MKL2 MKL/myocardin-like 2 1.659162 0.00390191

ING2 inhibitor of growth family, member 2 1.657729 0.02121174

CCDC144A coiled-coil domain containing 144 A 1.657432 0.00173654

DNHD1 dynein heavy chain domain 1 1.657184 0.01566451

WDR91 WD repeat domain 91 1.656314 0.0315293

CYB561D1 cytochrome b-561 domain containing 1 1.656224 0.01791395

PRDM15 PR domain containing 15 1.655236 0.01158217 inositol 1,4, -triphosphate receptor interacting

ITPRIP protein 1.655234 0.03688571

GAGE1 G antigen 1 1.655031 0.00514216

ANKRD26 ankyrin repeat domain 26 1.654533 0.02552525

ZNF142 zinc finger protein 142 1.654022 0.00078112

RNF43 Ring finger protein 43 1.65396 0.02379895

WDR75 WD repeat domain 75 1.653748 0.0495029

POLK polymerase (DNA directed) kappa 1.653549 0.01193697

HIST1H4L histone cluster 1, H41 1.652972 0.04865703 intraflagellar transport 81 homolog

IFT81 (Chlamydomonas) 1.652245 0.0468978 proteasome (prosome, macropain) assembly

PSMG2 chaperone 2 1.652182 0.01 16722

C19orfl5 Chromosome 19 open reading frame 15 1.652015 0.0338281 calcium channel, voltage-dependent, gamma

CACNG1 subunit 1 1.650647 0.04021915

WWC2 WW and C2 domain containing 2 1.648889 0.04777825

DCP2 decapping enzyme homolog (S.

DCP2 cerevisiae) 1.648793 0.0231128

KRT12 keratin 12 1.648711 0.02722292

AN03 anoctamin 3 1.647576 0.02231733

TOR1AIP2 torsin A interacting protein 2 1.647022 0.03031937

DENR density-regulated protein 1.64684 0.00919117 cytochrome P450, family 1, subfamily B,

CYP1B1 polypeptide 1 1.646677 0.00867029

RNF214 ring finger protein 214 1.645844 0.01485931

RPL12 ribosomal protein L12 1.645702 0.03148393

SHPRH SNF2 histone linker PHD RING helicase 1.645516 0.03755224

GSK3B glycogen synthase kinase 3 beta 1.644466 0.04817556

Small inducible cytokine subfamily E,

SCYE1 member 1 (endothelial monocyte-activating) 1.64437 0.00803724 neural precursor cell expressed,

NEDD9 developmentally down-regulated 9 1.644364 0.04275758

DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

LI CAM LI cell adhesion molecule 1.644025 0.00530349

STK38 serine/threonine kinase 38 1.642924 0.01632112

PPCS phosphopantothenoylcysteine synthetase 1.642528 0.0195829

PSAP prosaposin 1.642419 0.03606651

ZCCHC6 zinc finger, CCHC domain containing 6 1.64235 0.02301349

SYT10 Synaptotagmin X 1.642079 0.0298561

DNAH1 Dynein, axonemal, heavy chain 1 1.641795 0.02199322

MAP2K5 mitogen-activated protein kinase kinase 5 1.641555 0.00543911

MRPS5 mitochondrial ribosomal protein S5 1.641288 0.02848696

G-protein signaling modulator 3 (AGS3-like,

GPSM3 C. elegans) 1.641236 0.04995749 MRPL20 Mitochondrial ribosomal protein L20 1.641024 0.02461408

ELAV (embryonic lethal, abnormal vision,

ELAVL1 Drosophila)-like 1 (Hu antigen R) 1.640597 0.03564955 TAGLN transgelin 1.640518 0.04817693 ACTL6A actin-like 6A 1.640505 0.04155384 C20orfl l4 chromosome 20 open reading frame 114 1.639829 0.00887036 caspase recruitment domain family, member

CARD11 11 1.639374 0.01315459

SCML2 sex comb on midleg-like 2 (Drosophila) 1.639341 0.03583245

TNS3 tensin 3 1.639279 0.02617119

ATXN7L1 Ataxin 7-like 1 1.63894 0.00322217

NPHP3 nephronophthisis 3 (adolescent) 1.638935 0.00341519

NSUN5B NOLl/NOP2/Sun domain family, member 5B 1.638557 0.00035345

AES amino-terminal enhancer of split 1.638478 0.04945512

EDC4 enhancer of mRNA decapping 4 1.638271 0.03325857 v-raf murine sarcoma viral oncogene homolog

BRAF Bl 1.638003 0.03531981 solute carrier organic anion transporter

SLC02A1 family, member 2A1 1.637127 0.0265858

Src homology 3 domain-containing guanine

SGEF nucleotide exchange factor 1.636679 0.01072911 phosphatidylinositol glycan anchor

PIGK biosynthesis, class K 1.6363 0.00319759

SETBP1 SET binding protein 1 1.63618 0.00590179

GEN1 Gen homolog 1 , endonuclease (Drosophila) 1.635816 0.02891478

APOB apo lipoprotein B (including Ag(x) antigen) 1.635177 0.03837457

KLB klotho beta 1.634465 0.00022703 integrin, alpha E (antigen CD 103, human

mucosal lymphocyte antigen 1 ; alpha

ITGAE polypeptide) 1.634074 0.03995079

Biphenyl hydrolase-like (serine hydrolase;

BPHL breast epithelial mucin-associated antigen) 1.633697 0.01337344

CXorf58 chromosome X open reading frame 58 1.63358 0.00778154

ACTB actin, beta 1.633494 0.04468234 aldehyde dehydrogenase 3 family, member

ALDH3B1 Bl 1.63275 0.00741251 SUFU suppressor of fused homolog (Drosophila) 1.632133 0.01242218

ST8 alpha-N-acetyl-neuraminide alpha-2,8-

ST8SIA4 sialyltransferase 4 1.631566 0.03915633

DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value protein tyrosine phosphatase, non-receptor

PTPN14 type 14 1.63156 0.04046252

GIN1 gypsy retrotransposon integrase 1 1.631327 0.03380499

MTIF2 mitochondrial translational initiation factor 2 1.631234 0.04677842

DNAL4 dynein, axonemal, light chain 4 1.630824 0.00553133

ZBTB40 zinc finger and BTB domain containing 40 1.630804 0.0346299

Cl lorfl Chromosome 11 open reading frame 1 1.630803 0.02442311

KIAA0247 IAA0247 1.630564 0.03640115

ATP4B ATPase, H+/K+ exchanging, beta polypeptide 1.629612 0.04978088

ADAM metallopeptidase with

ADAMTS6 thrombospondin type 1 motif, 6 1.629112 0.01365261

CCDC24 coiled-coil domain containing 24 1.629028 0.03641167

SPEF2 sperm flagellar 2 1.628671 0.02751741

MMP23A matrix metallopeptidase 23A (pseudogene) 1.628276 0.00795961

GPR124 G protein-coupled receptor 124 1.628088 0.03794903

DEAD (Asp-Glu-Ala-Asp) box polypeptide

DDX56 56 1.627335 0.03177008

ADP-ribosylation-like factor 6 interacting

ARL6IP6 protein 6 1.627215 0.03755756 leucine-rich repeats and WD repeat domain

LRWD1 containing 1 1.626571 0.03027413 CXorf22 chromosome X open reading frame 22 1.626407 0.04193664

UDP-N-acetyl-alpha-D- galactosamine:polypeptide N- acetylgalactosaminyltransferase 1 (GalNAc-

GALNT1 Tl) 1.626164 0.03763074 megalencephalic leukoencephalopathy with

MLC1 subcortical cysts 1 1.625926 0.0132559

NCRNA0008

3 non-protein coding R A 83 1.625919 0.00905639

MRPL41 mitochondrial ribosomal protein L41 1.625633 0.0209388 inhibitor of Bruton agammaglobulinemia

IBTK tyrosine kinase 1.625579 0.01834248 COL27A1 collagen, type XXVII, alpha 1 1.625164 0.02639891 angiogenic factor with G patch and FHA

AGGF1 domains 1 1.624279 0.04569015

LPCAT1 lysophosphatidylcholine acyltransferase 1 1.624191 0.04338435

TMEM30A transmembrane protein 30A 1.62414 0.00774066

Γ Ο80Β INO80 complex subunit B 1.623832 0.04070508

C6orfl Chromosome 6 open reading frame 1 1.623349 0.04350354

GAD1 glutamate decarboxylase 1 (brain, 67kDa) 1.622848 0.02366237

ITPR3 inositol 1 ,4,5-triphosphate receptor, type 3 1.62276 0.02131997

RANBP3 RAN binding protein 3 1.622539 0.02211052

TRIM37 tripartite motif-containing 37 1.622298 0.0271814

TTC37 tetratricopeptide repeat domain 37 1.622054 0.02753881

TFRC transferrin receptor (p90, CD71) 1.621364 0.02335426

HMCN1 hemicentin 1 1.6206 0.03558657

NUP153 nucleoporin 153kDa 1.619972 0.02029782

AFAP1 actin filament associated protein 1 1.619608 0.04847107

ZSCAN16 zinc finger and SCAN domain containing 16 1.619254 0.03603056

DB l/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

RPS6KL1 ribosomal protein S6 kinase-like 1 1.619011 0.01727224 translocation associated membrane protein 1 -

TRAM1L1 like 1 1.618507 0.04921298

C14orf45 Chromosome 14 open reading frame 45 1.618112 0.00555711

PLCGl phospholipase C, gamma 1 1.617724 0.01886621

BAT2L N/A 1.617581 0.02508675

GAK cyclin G associated kinase 1.616995 0.04650567 euchromatic histone-lysine N-

EHMT2 methyltransferase 2 1.616535 0.00569505

DnaJ (Hsp40) homolog, subfamily C, member

DNAJC13 13 1.616418 0.01480203

PARP1 poly (ADP-ribose) polymerase 1 1.616079 0.0046287

MFF mitochondrial fission factor 1.615445 0.04236204

C17orf28 Chromosome 17 open reading frame 28 1.615205 0.01857967

SSFA2 sperm specific antigen 2 1.613665 0.03156742

INTS10 integrator complex subunit 10 1.61321 0.03759633

DEAD (Asp-Glu-Ala-Asp) box polypeptide

DDX41 41 1.613103 0.01994811 SP7 Sp7 transcription factor 1.612873 0.03503308

LOC348840 hypothetical LOC348840 1.612318 0.0333923 Clorf64 chromosome 1 open reading frame 64 1.61183 0.03787225 TD02 tryptophan 2,3-dioxygenase 1.611314 0.02656894 CAV1 caveolin 1 , caveolae protein, 22kDa 1.611044 0.02082052

Williams-Beuren syndrome chromosome

WBSCR28 region 28 1.610314 0.00484965

PCGF3 polycomb group ring finger 3 1.609233 0.04500391

LYPD1 LY6/PLAUR domain containing 1 1.60869 0.0035166

PTPRC protein tyrosine phosphatase, receptor type, C 1.608622 0.04671333

CSNK1G1 casein kinase 1, gamma 1 1.608354 0.02852645

Protein phosphatase 1, regulatory (inhibitor)

PPP1R9B subunit 9B 1.608304 0.04955725

DNM2 dynamin 2 1.60777 0.00414141

DUSP1 dual specificity phosphatase 1 1.607697 0.04177325 solute carrier family 22 (organic anion

SLC22A8 transporter), member 8 1.607396 0.00196477

MIT, microtubule interacting and transport,

MITD1 domain containing 1 1.60683 0.04251328

ACHE acetylcholinesterase (Yt blood group) 1.606818 0.03555008

AMBRA1 autophagy/beclin- 1 regulator 1 1.60667 0.0180331 1

NT5C3 5'-nucleotidase, cytosolic III 1.606528 0.03931726

Clorf94 chromosome 1 open reading frame 94 1.606141 0.02028391 vacuolar protein sorting 4 homolog A (S.

VPS4A cerevisiae) 1.606059 0.01278086 CHML choroideremia-like (Rab escort protein 2) 1.605833 0.00700314 LMNA lamin A/C 1.605628 0.03179212 NUP54 nucleoporin 54kDa 1.605456 0.01761976 HBP1 HMG-box transcription factor 1 1.605236 0.03723468 glutamate receptor, ionotropic, N-methyl D- aspartate-associated protein 1 (glutamate

GRINA binding) 1.605053 0.02558557 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upreguiated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

CYB5RL cytochrome b5 reductase-Hke 1.604601 0.04650936 glucocorticoid modulatory element binding

GMEB2 protein 2 1.604463 0.0140619 xeroderma pigmentosum, complementation

XPC group C 1.604321 0.02637103

PLXNB3 plexin B3 1.603875 0.03721121

C14orfl02 chromosome 14 open reading frame 102 1.603636 0.02439481 solute carrier family 30 (zinc transporter),

SLC30A5 member 5 1.603386 0.01412032 lipid phosphate phosphatase-related protein

LPPR2 type 2 1.602546 0.01890624 FLJ44653 shadow of prion protein pseudogene 1.602295 0.01487034

FXYD domain containing ion transport

FXYD5 regulator 5 1.601868 0.02767412 NSUN2 NOP2/Sun domain family, member 2 1.601739 0.03789891

IMP (inosine 5'-monophosphate)

IMPDH1 dehydrogenase 1 1.601557 0.02390004

RAD17 RAD17 homolog (S. pombe) 1.601375 0.0208996

MPG N-methylpurine-DNA glycosylase 1.601321 0.0278861

PDE4DIP phosphodiesterase 4D interacting protein 1.600681 0.03762262

AGTPBP1 ATP/GTP binding protein 1 1.600172 0.04242109

NADH dehydrogenase (ubiquinone) Fe-S

protein 1, 75kDa (NADH-coenzyme Q

NDUFS1 reductase) 1.600136 0.00377063 IAA1432 KIAA1432 1.599882 0.01279288 fibroblast growth factor (acidic) intracellular

FIBP binding protein 1.599584 0.00865392

SDCBP2 syndecan binding protein (syntenin) 2 1.599528 0.04436837

TM9SF2 transmembrane 9 superfamily member 2 1.599129 0.0469163 serrate RNA effector molecule homolog

SRRT (Arabidopsis) 1.598778 0.04748051

KIAA1804 mixed lineage kinase 4 1.5985 0.01465947

SRGAP3 SLIT-ROBO Rho GTPase activating protein 3 1.598109 0.02406393

DLG2 discs, large homolog 2 (Drosophila) 1.59803 0.04648955

PLN phospholamban 1.597774 0.03369263

BIN2 bridging integrator 2 1.596659 0.03630293

AUTS2 autism susceptibility candidate 2 1.596405 0.01840948

CFI complement factor I 1.596392 0.0081991

GTPase activating protein (SH3 domain)

G3BP2 binding protein 2 1.595921 0.03007079 PI4KB phosphatidylinositol 4-kinase, catalytic, beta 1.595832 0.01455479 family with sequence similarity 174, member

FAM174A A 1.59576 0.03603914

SNX13 sorting nexin 13 1.595744 0.03359426

STAG3 stromal antigen 3 1.595647 0.04932906

PRP8 pre-mRNA processing factor 8

PRPF8 homolog (S. cerevisiae) 1.595386 0.02456534 DOCK8 dedicator of cytokinesis 8 1.595294 0.02519439 WDR37 WD repeat domain 37 1.594727 0.00378112 CD 180 CD 180 molecule 1.59426 0.00270468

DB1/ 69437₅16.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

LRRC39 leucine rich repeat containing 39 0.04469574

HOXA3 homeobox A3 0.03851359

C3orf63 chromosome 3 open reading frame 63 0.04996988

NRG1 neuregulin 1 0.02057303

KDM4A lysine (K)-specific demethylase 4A 0.00806626

RARS arginyl-tRNA synthetase 0.02013136 heat shock protein family B (small), member

HSPB11 11 0.04902965

UNQ3028 N/A 0.04928276

IQCB1 IQ motif containing Bl 0.03315168 hypoxia inducible factor 1, alpha subunit

HIF1A (basic helix-loop-helix transcription factor) 1.591415 0.00884964

ArfGAP with GTPase domain, ankyrin repeat

AGAP4 and PH domain 4 0.0332583

IFNAR2 interferon (alpha, beta and omega) receptor 2 0.00484284

WDR35 WD repeat domain 35 0.00790004

MTCH1 mitochondrial carrier homolog 1 (C. elegans) 0.04063505

CCDC54 coiled-coil domain containing 54 0.03288872

FAF2 Fas associated factor family member 2 0.0271 1297 oxidative stress induced growth inhibitor

OSGIN2 family member 2 0.02519466

KIAA1949 KIAA1949 0.04098394

PADI1 peptidyl arginine deiminase, type I 0.04804845 calcium channel, voltage-dependent, P/Q

CACNA1A type, alpha 1A subunit 1.58815 0.02091973

FERM, RhoGEF (ARHGEF) and pleckstrin

FARP1 domain protein 1 (chondrocyte-derived) 0.04607572 C22orf34 chromosome 22 open reading frame 34 0.01101082 class II, major histocompatibility complex,

CIITA transactivator .586799 0.02529807

TAF9 RNA polymerase II, TATA box

binding protein (TBP)-associated factor,

TAF9 32kDa 1.586724 0.04658612 nuclear autoantigenic sperm protein (histone-

NASP binding) 0.02198518

KIRREL2 Kin of IRRE like 2 (Drosophila) 0.01097234

FADS2 Fatty acid desaturase 2 0.00033349

NF1 neurofibromin 1 0.03828146

CTSA cathepsin A 0.04152232

P4HA1 prolyl 4-hydroxylase, alpha polypeptide I 0.02420803

RFC 5 replication factor C (activator 1) 5, 36.5kDa 0.00493414

ZNF655 zinc finger protein 655 0.03282984

PRLH prolactin releasing hormone 0.03987318

CCDC146 coiled-coil domain containing 146 0.04435089

Bromodomain and WD repeat domain

BRWD2 containing 2 0.01008763

BTN2A2 butyrophilin, subfamily 2, member A2 0.03770244

TRIM58 tripartite motif-containing 58 0.02235746

KLK15 Kallikrein-related peptidase 15 0.02715313

OARS glutaminyl-tRNA synthetase 0.0125861 1 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

CXCR4 chemokine (C-X-C motif) receptor 4 1.580898 0.04082367 cytochrome P450, family 3, subfamily A,

CYP3A4 polypeptide 4 1.580699 0.04268473

NBAS neuroblastoma amplified sequence 1.580693 0.00388638

Clorf87 chromosome 1 open reading frame 87 1.580614 0.00863699

EXOC3L2 exocyst complex component 3 -like 2 1.580241 0.00834036

PTPRM protein tyrosine phosphatase, receptor type, M 1.580029 0.00732594

LIMD2 LIM domain containing 2 1.579849 0.03016734

Smg-5 homolog, nonsense mediated mRNA

SMG5 decay factor (C. elegans) 1.579435 0.0010077

C21orf91 chromosome 21 open reading frame 91 1.579127 0.03847725

ZNF663 Zinc finger protein 663 1.578963 0.03550333

EIF2C2 eukaryotic translation initiation factor 2C, 2 1.578877 0.02885005

GPR113 G protein-coupled receptor 113 1.578257 0.03397636

LYPLA2 lysophospholipase II 1.577251 0.04735262

IQWD1 IQ motif and WD repeats 1 1.576988 0.01881598 membrane bound O-acyltransferase domain

MB OAT 1 containing 1 1.57594 0.03236491 TTLL2 tubulin tyrosine ligase-like family, member 2 1.575766 0.0307972

ATPase, aminophospholipid transporter

ATP8A1 (APLT), class I, type 8A, member 1 1.575492 0.01557476

Ras protein-specific guanine nucleotide-

RASGRF2 releasing factor 2 1.575085 0.0447572 guanine nucleotide binding protein (G

GNA11 protein), alpha 11 (Gq class) 1.575028 0.0024914

Olfactory receptor, family 52, subfamily B,

OR52B6 member 6 1.575011 0.01759295

CDC42 binding protein kinase beta (DMPK-

CDC42BPB like) 1.574939 0.00935113

CD300LG CD300 molecule-like family member g 1.574229 0.00222999

KNTC1 kinetochore associated 1 1.573628 0.03209189

DEPDC4 DEP domain containing 4 1.573049 0.03533614

SHQ1 SHQ1 homolog (S. cerevisiae) 1.572124 0.03773088

MACC1 metastasis associated in colon cancer 1 1.571743 0.03047397

GOLM1 golgi membrane protein 1 1.571733 0.01360222

LRRC37B2 leucine rich repeat containing 37, member B2 1.571699 0.02532213

COL5A2 collagen, type V, alpha 2 1.5714 0.0309551 1

TP53BP1 tumor protein p53 binding protein 1 1.571121 0.03849533

ClOorf O chromosome 10 open reading frame 90 1.570911 0.01054486 phospholipase C, beta 1 (phosphoinositide-

PLCB1 specific) 1.569662 0.04119316

ANKRD32 ankyrin repeat domain 32 1.569041 0.02424598

RBM34 RNA binding motif protein 34 1.568797 0.00559575 carboxyl ester lipase (bile salt-stimulated

CEL lipase) 1.568045 0.03937509 ANXA1 annexin Al 1.567821 0.00977338 core 1 synthase, glycoprotein-N- acetylgalactosamine 3-beta-

C1GALT1 galactosyltransferase, 1 1.567234 0.04435706 FAT1 FAT tumor suppressor homolog 1 1.566978 0.01950681 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

(Drosophila)

general transcription factor IIIC, polypeptide

GTF3C1 1, alpha 220kDa 1.565863 0.03390878 ATMIN ATM interactor 1.565673 0.02568693 PNPT1 polyribonucleotide nucleotidyltransferase 1 1.565445 0.03732588 transcription elongation factor B polypeptide

TCEB3C 3C (elongin A3) 1.565293 0.04760489 KLK3 kallikrein-related peptidase 3 1.565237 0.01348915 potassium voltage-gated channel, subfamily

KCNF1 F, member 1 1.564143 0.02834103

MTA2 metastasis associated 1 family, member 2 1.563827 0.01761642

CBR4 carbonyl reductase 4 1.563764 0.0326285

C14orfl59 chromosome 14 open reading frame 159 1.563717 0.00169098

INTS7 integrator complex subunit 7 1.563662 0.04482643

SFTPC surfactant protein C 1.562999 0.01436025

PDE10A phosphodiesterase 10A 1.562608 0.02091243

ZKSCAN5 zinc finger with KRAB and SCAN domains 5 1.562567 0.00508912

EMID1 EMI domain containing 1 1.562191 0.00782405

AMPH amphiphysin 1.562135 0.0154874

NPIP nuclear pore complex interacting protein 1.562071 0.01869195

MTMR10 myotubularin related protein 10 1.561932 0.0103955 damage-specific DNA binding protein 1,

DDB1 127kDa 1.561316 0.00746873 GATAD2B GATA zinc finger domain containing 2B 1.560948 0.04069536 solute carrier family 12

(sodium/potassium/chloride transporters),

SLC12A2 member 2 1.560775 0.02096845 PDLIM7 PDZ and LIM domain 7 (enigma) 1.560624 0.01849702 RNF38 ring finger protein 38 1.560505 0.03660505 NOTCH4 Notch homolog 4 (Drosophila) 1.560209 0.02750535 solute carrier family 6 (neurotransmitter

SLC6A13 transporter, GAB A), member 13 1.560159 0.02092643 ARL8A ADP-ribosylation factor-like 8A 1.55933 0.02476569

DIP2 disco-interacting protein 2 homolog C

DIP2C (Drosophila) 1.559135 0.0306571

TBR1 T-box, brain, 1 1.558615 0.00973385

DOCK5 dedicator of cytokinesis 5 1.558612 0.0134413 family with sequence similarity 113, member

FAM113A A 1.558557 0.03275575

ZBTB1 zinc finger and BTB domain containing 1 1.558397 0.00183477

KRT23 Keratin 23 (histone deacetylase inducible) 1.558175 0.0148528

DKFZp434Fl

42 hypothetical DKFZp434F142 1.558166 0.03025031

Clorf96 chromosome 1 open reading frame 96 1.557442 0.00313993 MICALCL MICAL C-terminal like 1.557271 0.02847193

ADAM metallopeptidase with

ADAMTS20 thrombospondin type 1 motif, 20 1.557258 0.01814664 tumor necrosis factor (ligand) superfamily,

TNFSF13 member 13 1.556484 0.03059729 CAPRJN1 cell cycle associated protein 1 1.556445 0.01908969

DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

INPP5J inositol polyphosphate-5-phosphatase J 1.556265 0.0041265

Amyotrophic lateral sclerosis 2 (juvenile)

ALS2CR1 1 chromosome region, candidate 1 1 1.555369 0.04529981

MAN1A1 mannosidase, alpha, class 1 A, member 1 1.554765 0.01354809

EPB41L5 erythrocyte membrane protein band 4.1 like 5 1.554615 0.00348279

ZNF445 zinc finger protein 445 1.554576 0.01779286

EMCN endomucin 1.554188 0.03905193

MAP2 microtubule-associated protein 2 1.55383 0.03204381

DNA cross-link repair 1A (PS02 homolog, S.

DCLRE1A cerevisiae) 1.553638 0.03995784 MFAP3 microfibrillar-associated protein 3 1.553195 0.04737588 RAVER 1 Ribonucleoprotein, PTB-binding 1 1.552791 0.00727941 NCAPG non-SMC condensin I complex, subunit G 1.552663 0.03554067 WDR41 WD repeat domain 41 1.551501 0.00269208 calcium homeostasis endoplasmic reticulum

CHERP protein 1.551363 0.01319

DVL3 dishevelled, dsh homolog 3 (Drosophila) 1.551 189 0.03796681

FRAS 1 Fraser syndrome 1 1.551065 0.00045573

ANKRD13D ankyrin repeat domain 13 family, member D 1.55101 1 0.00199369

DES desmin 1.549738 0.01271598

E2F5 E2F transcription factor 5, pl30-binding 1.549601 0.03693464 phosphatidylinositol-5 -phosphate 4-kinase,

PIP4K2C type II, gamma 1.549431 0.03481636

ZDHHC3 zinc finger, DHHC-type containing 3 1.549004 0.00761689

UHRF1BP1L UHRF1 binding protein 1 -like 1.548447 0.00697566

WDR49 WD repeat domain 49 1.548196 0.0134696

YTHDF3 YTH domain family, member 3 1.548102 0.02135835

Src homology 2 domain containing adaptor

SHB protein B 1.547684 0.00084426

CLEC 18C C-type lectin domain family 18, member C 1.547543 0.0110041 1 protein tyrosine phosphatase, non-receptor

PTPN2 type 2 1.54739 0.02035435 ZNF354B zinc finger protein 354B 1.547163 0.01684084 ABHD3 abhydrolase domain containing 3 1.547037 0.04585433 TSLP thymic stromal lymphopoietin 1.546812 0.0157549

ADAM metallopeptidase with

ADAMTS9 thrombospondin type 1 motif, 9 1.54551 1 0.00347952

GRHL1 grainyhead-like 1 (Drosophila) 1.544812 0.04849137

AQR aquarius homolog (mouse) 1.544351 0.01005732 diacylglycerol O-acyltransferase homolog 1

DGAT1 (mouse) 1.54416 0.01906196

ORMDL1 ORMl-like 1 (S. cerevisiae) 1.54414 0.02275899

TBC1D21 TBC1 domain family, member 21 1.543774 0.04418519

NCR3 natural cytotoxicity triggering receptor 3 1.543416 0.02868302

PCDH1 protocadherin 1 1.543274 0.04368429

GPR56 G protein-coupled receptor 56 1.542173 0.04121757

CPT1A carnitine palmitoyltransferase 1 A (liver) 1.541995 0.0455955

DNMBP dynamin binding protein 1.54178 0.01037482

NT5DC1 5 '-nucleotidase domain containing 1 1.541535 0.01224804

BTNL8 butyrophilin-like 8 1.541439 0.00940871

DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

PZP pregnancy-zone protein 0.04044797

RGAG1 retrotransposon gag domain containing 1 0.04310469

ZNF248 Zinc finger protein 248 0.03294884

Cas-Br-M (murine) ecotropic retroviral

CBLB transforming sequence b 0.02728626 TMEM39A transmembrane protein 39A 0.02298178 glucosaminyl (N-acetyl) transferase 3, mucin

GCNT3 type 0.04765364 MMP19 matrix metallopeptidase 19 0.02127341 C19orf55 chromosome 19 open reading frame 55 0.02031633 ZNF639 zinc finger protein 639 0.03676195

Zic family member 5 (odd-paired homolog,

ZIC5 Drosophila) 0.00518347

TUFT1 tuftelin 1 0.04381125

ALK anaplastic lymphoma receptor tyrosine kinase 0.03566215

FCH02 FCH domain only 2 0.00085839

NFIA nuclear factor I/A 0.04313686

PAK2 p21 protein (Cdc42/Rac)-activated kinase 2 0.03014228

UIMC1 ubiquitin interaction motif containing 1 0.0111732

MANEAL mannosidase, endo-alpha-like 0.00444797

PSD3 pleckstrin and Sec7 domain containing 3 0.04330975

ATF6B activating transcription factor 6 beta 0.03667598

IP6K2 inositol hexakisphosphate kinase 2 0.01536192 mitogen-activated protein kinase 8 interacting

MAPK8IP3 protein 3 0.00633798 ZBTB9 zinc finger and BTB domain containing 9 0.01918224

Stress-associated endoplasmic reticulum

SERP1 protein 1 0.00112698 UBA2 ubiquitin-like modifier activating enzyme 2 0.03719408 C15orf33 chromosome 15 open reading frame 33 0.03807529 inhibitor of CDK, cyclin Al interacting

INCA1 protein 1 0.04573421

SFT2D3 SFT2 domain containing 3 0.03043152

DPEP3 dipeptidase 3 0.01954245

HEG1 HEG homolog 1 (zebrafish) 0.0324556

GLOl glyoxalase I 0.04519109

UTP15, U3 small nucleolar

UTP15 ribonucleoprotein, homolog (S. cerevisiae) 0.01108262

C19orf50 chromosome 19 open reading frame 50 0.02943876

ARSF arylsulfatase F 0.0186262 transforming growth factor beta 1 induced

TGFB1I1 transcript 1 1.533844 0.04888081 protein disulfide isomerase family A, member

PDIA6 6 0.01326546 PPA2 pyrophosphatase (inorganic) 2 0.01586952

CDK5RAP3 CDK5 regulatory subunit associated protein 3 0.02254633

UDP-N-acetyl-alpha-D- galactosamine:polypeptide N-

GALNTL4 acetylgalactosaminyltransferase-like 4 0.04491059 RTEL1 regulator of telomere elongation helicase 1 0.01527838

DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

BCL9L B-cell CLL/lymphoma 9-like 1.531991 0.0045904

GB AS glioblastoma amplified sequence 1.531 88 0.00296838

NCOA3 nuclear receptor coactivator 3 1.531259 0.00465947

ROPN1L ropporin 1 -like 1.530537 0.01192305

CXorf23 chromosome X open reading frame 23 1.530431 0.03105831

APOA2 apolipoprotein A-II 1.53024 0.03723402

ACADVL acyl-CoA dehydrogenase, very long chain 1.529945 0.02404657 integrin, alpha V (vitronectin receptor, alpha

ITGAV polypeptide, antigen CD51) 1.529921 0.02992868

ZNF672 zinc finger protein 672 1.529868 0.01291179

C9orfl 50 chromosome 9 open reading frame 150 1.529094 0.01511257

SSPO SCO-spondin homolog (Bos taurus) 1.529074 0.04138227

RGS7 regulator of G-protein signaling 7 1.528987 0.01630161

HAUS4 HAUS augmin-like complex, subunit 4 1.528799 0.04476215

CALCR calcitonin receptor 1.528616 0.00181452

SPATA3 Spermatogenesis associated 3 1.528332 0.00385196

LCLAT1 lysocardiolipin acyltransferase 1 1.527877 0.04339041

STK17B serine/threonine kinase 17b 1.527719 0.03760197

Clorfl98 chromosome 1 open reading frame 198 1.527608 0.01535303

AFF4 AF4/FMR2 family, member 4 1.527321 0.02022046

C3orfl5 chromosome 3 open reading frame 15 1.52695 0.04424073

GTPBP8 GTP-binding protein 8 (putative) 1.526699 0.02764528 cleft lip and palate associated transmembrane

CLPTM1 protein 1 1.526502 0.03479322 solute carrier family 4, sodium bicarbonate

SLC4A10 transporter, member 10 1.526501 0.04084261

MKRN3 makorin ring finger protein 3 1.526045 0.0085596

PIM1 pirn- 1 oncogene 1.525922 0.0424031 1

RAB23 RAB23, member RAS oncogene family 1.52539 0.01869873

ZFY zinc finger protein, Y-linked 1.525336 0.0029304

PCSK7 proprotein convertase subtilisin/kexin type 7 1.52515 0.00584015 phospholipase A2, group IVC (cytosolic,

PLA2G4C calcium-independent) 1.52491 0.02842672

KIAA1279 KIAA1279 1.524763 0.01136681

ANKRD35 ankyrin repeat domain 35 1.524669 0.02594497

UDP glucuronosyltransferase 1 family,

UGT1A7 polypeptide A7 1.524507 0.04652272

Usher syndrome 1C (autosomal recessive,

USH1C severe) 1.524293 0.00891889

CDC42SE1 CDC42 small effector 1 1.524227 0.02124608

MKRN2 makorin ring finger protein 2 1.524163 0.04756701

LAS1L LASl-like (S. cerevisiae) 1.523924 0.0047693

WDR66 WD repeat domain 66 1.523336 0.03741995

RICH2 Rho-type GTPase-activating protein RICH2 1.523316 0.00911856

FAM76B family with sequence similarity 76, member B 1.523274 0.03193599

ZNF616 zinc fmger protein 616 1.523196 0.01759284

FZD10 frizzled homolog 10 (Drosophila) 1.523097 0.03396822 nuclear factor of kappa light polypeptide gene

NFKBIZ enhancer in B-cells inhibitor, zeta 1.522876 0.01551464

KLHDC2 kelch domain containing 2 1.522313 0.02042568 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

IRAKI interleukin-1 receptor-associated kinase 1 1.522241 0.00602997

FANCA Fanconi anemia, complementation group A 1.522057 0.02479576

TNS1 tensin 1 1.521956 0.03592733 inner centromere protein antigens

INCENP 135/155kDa 1.521596 0.00926599

Ral GEF with PH domain and SH3 binding

RALGPS2 motif 2 1.521416 0.00618193

GPR128 G protein-coupled receptor 128 1.520965 0.00372652

FLJ37396 hypothetical protein FL.T37396 1.520372 0.04538205

SP140L SP140 nuclear body protein-like 1.520204 0.02461727

ACVR2A activin A receptor, type IIA 1.519658 0.0083885

GLT25D2 glycosyltransferase 25 domain containing 2 1.519436 0.03927104

C2orf63 chromosome 2 open reading frame 63 1.519398 0.00148009

DYNC1H1 dynein, cytoplasmic 1 , heavy chain 1 1.519287 0.02522096

PMSl postmeiotic segregation increased 1 (S.

PMSl cerevisiae) 1.51918 0.04248844

KIAA1324 KIAA1324 1.518936 0.03849599

C21orf90 chromosome 21 open reading frame 90 1.518365 0.03883319

ATPase, H+ transporting, lysosomal V0

ATP6V0A4 subunit a4 1.518126 9.30E-06

HIG1 hypoxia inducible domain family,

HIGD1A member 1A 1.518117 0.0008097 solute carrier family 6 (neurotransmitter

SLC6A4 transporter, serotonin), member 4 1.517608 0.03883098 mannosyl (alpha-l,3-)-glycoprotein beta-1,4-

MGAT4A N-acetylglucosaminyltransferase, isozyme A 1.517593 0.01744339

CDP-diacylglycerol—inositol 3-

CDIPT phosphatidyltransferase 1.517408 0.04511741 colony stimulating factor 2 receptor, beta,

CSF2RB low-affinity (granulocyte-macrophage) 1.517362 0.04008848

HOXA9 homeobox A9 1.517045 0.04696364

MAN2A1 mannosidase, alpha, class 2A, member 1 1.516951 0.0270042 family with sequence similarity 82, member

FAM82A1 Al 1.516347 0.01479676

ETV5 ets variant 5 1.516057 0.04481994

RPS10 ribosomal protein S10 1.516017 0.02906973 aldehyde dehydrogenase 8 family, member

ALDH8A1 Al 1.515699 0.03066374

TMEM48 transmembrane protein 48 1.514852 0.04795775 glutamate decarboxylase 2 (pancreatic islets

GAD2 and brain, 65kDa) 1.514642 0.03182126

PCDH15 Protocadherin 1 1.514612 0.04382075 transmembrane emp24 protein transport

TMED4 domain containing 4 1.514565 0.04591312 calcium channel, voltage-dependent, alpha

CACNA2D1 2/delta subunit 1 1.514413 0.00568028

ALPL alkaline phosphatase, liver/bone/kidney 1.514321 0.0280432

TGM6 transglutaminase 6 1.514171 0.02168385

KIAA1109 KIAA1109 1.51414 0.01690086

PARP9 poly (ADP-ribose) polymerase family, 1.513927 0.03008991

DB l/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value member 9

olfactory receptor, family 5, subfamily I,

OR5I1 member 1 1.51391 0.03273026

FBN3 Fibrillin 3 1.513639 0.03689208 ribosomal protein S6 kinase, 90kDa,

RPS6KA3 polypeptide 3 1.513578 0.04127709 non-metastatic cells 7, protein expressed in

NME7 (nucleoside-diphosphate kinase) 1.513493 0.01033888

WDR36 WD repeat domain 36 1.51338 0.03790186

IFRD1 interferon-related developmental regulator 1 1.512674 0.02802167

GM2A GM2 ganglioside activator 1.512602 0.03087316

MCPH1 Microcephalin 1 1.512198 0.02307828

RNF207 ring finger protein 207 1.511946 0.006231 1

IQSEC1 IQ motif and Sec7 domain 1 1.51151 0.02037703

UDP glucuronosyltransferase 1 family,

UGT1A9 polypeptide A9 1.511159 0.02271588

POLQ polymerase (DNA directed), theta 1.510962 0.03235888

MRPS33 mitochondrial ribosomal protein S33 1.510729 0.02680392

DYX1C1 dyslexia susceptibility 1 candidate 1 1.510621 0.01800952

TREXl Three prime repair exonuclease 1 1.510618 0.0479416

POMT2 protein-O-mannosyltransferase 2 1.510577 0.02206787

MAP7 microtubule-associated protein 7 1.51051 0.04421807

GPATCH4 G patch domain containing 4 1.510344 0.03298126

MTA1 metastasis associated 1 1.510324 0.02069066

Clorfl75 chromosome 1 open reading frame 175 1.510261 0.03674759

C5orf4 chromosome 5 open reading frame 4 1.509893 0.03555095 calcium/calmodulin-dependent serine protein

CASK kinase (MAGUK family) 1.509852 0.02504441

FLJ33534 hypothetical LOC285150 1.509641 0.00605129

SUSD1 sushi domain containing 1 1.509077 0.001 10171

MED12L mediator complex subunit 12-like 1.50899 0.00845126

ATP-binding cassette, sub-family A (ABCl),

ABCA4 member 4 1.508877 0.0360565

CTPS CTP synthase 1.508758 0.03235272

UGP2 UDP -glucose pyrophosphorylase 2 1.50845 0.04195768

UDP-N-acetyl-alpha-D- galactosamine:polypeptide N- acetylgalactosaminyltransferase 14 (GalNAc-

GALNT14 T14) 1.508233 0.00975996

C16orf82 chromosome 16 open reading frame 82 1.508071 0.01412293

ZMYND8 zinc finger, MYND-type containing 8 1.507935 0.0154587

GBA glucosidase, beta, acid 1.507121 0.0186475

MANSC1 MANSC domain containing 1 1.506913 0.03010828

MBD1 methyl-CpG binding domain protein 1 1.506387 0.01403498

C7orf50 chromosome 7 open reading frame 50 1.505924 0.01147375

NIMA (never in mitosis gene a)-related

NEK1 kinase 1 1.505029 0.00488555

TAF1 1 R A polymerase II, TATA box

binding protein (TBP)-associated factor,

TAF1 1 28kDa 1.504602 0.04250863

B 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

ST7L suppression of tumorigenicity 7 like 0.01399733

DNAH9 dynein, axonemal, heavy chain 9 0.04054231

TNP02 transportin 2 0.00026096

PSD4 pleckstrin and Sec7 domain containing 4 0.04978432

ABLIM3 actin binding LIM protein family, member 3 0.0297663

C6orfl42 chromosome 6 open reading frame 142 0.01949794 sulfotransferase family, cytosolic, 1A, phenol-

SULT1A3 preferring, member 3 0.04257144 CAPN3 calpain 3, (p94) 0.01986647 thymocyte selection-associated high mobility

TOX group box 0.02915765 ZNF205 zinc finger protein 205 0.00100172 chymotrypsin-like elastase family, member

CELA2A 2A 0.00239408

DLX5 distal-less homeobox 5 0.00306021

CCDC88A coiled-coil domain containing 88A 0.04767025

STOML1 stomatin (EPB72)-like 1 0.0280494

MID2 midline 2 0.0169234

CSGLCA-T Chondroitin sulfate glucuronyltransferase 0.01010816

P4HA2 prolyl 4-hydroxylase, alpha polypeptide II 0.0292032

MY06 myosin VI 0.04628552

GEMIN8 gem (nuclear organelle) associated protein 8 0.01700446

R ASEH2B ribonuclease H2, subunit B 0.02568195 solute carrier family 12 (potassium/chloride

SLC12A5 transporter), member 5 1.498932 0.04182994 cytochrome P450, family 20, subfamily A,

CYP20A1 polypeptide 1 0.00860486

BPTF bromodomain PHD finger transcription factor 0.0230048

PHTF2 Putative homeodomain transcription factor 2 0.01305125

ZBTB7A zinc finger and BTB domain containing 7A 0.01106742

PDK1 pyruvate dehydrogenase kinase, isozyme 1 0.01511556

KRTAPlO-10 keratin associated protein 10-10 0.01929623 SAP130 Sin3A-associated protein, 130kDa 0.0309965 C20orfl 1 chromosome 20 open reading frame 11 0.03218343 GPR162 G protein-coupled receptor 162 0.00727074

ArfGAP with RhoGAP domain, ankyrin

ARAP3 repeat and PH domain 3 0.03446676 FAM120B family with sequence similarity 120B 0.02053027 protein kinase, DNA-activated, catalytic

PRKDC polypeptide 1.496476 0.04042323 actin related protein 2/3 complex, subunit 1 A,

ARPC1A 41kDa 0.0273321

ATPase, Na+/K+ transporting, alpha 4

ATP1A4 polypeptide 0.00959306

TESSP2 Testis serine protease 2 0.04986434

ARHGDIB Rho GDP dissociation inhibitor (GDI) beta 0.04171769

TBC1D5 TBC1 domain family, member 5 0.04532486

SLTM SAFB-like, transcription modulator 0.02071 192

ALPK1 alpha-kinase 1 0.00084307

SLC37A1 solute carrier family 37 (glycerol-3 -phosphate 0.00887469

DB1/ 69₄37516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value transporter), member 1

VAV3 vav 3 guanine nucleotide exchange factor 1.49455 0.00863513 calcium channel, voltage-dependent, L type,

CACNA1D alpha ID subunit 1.494529 0.04770073 C17orf39 chromosome 17 open reading frame 39 1.494082 0.02305828 ventricular zone expressed PH domain

VEPH1 homolog 1 (zebrafish) 1.493979 0.00237279 VDAC1 voltage-dependent anion channel 1 1.493692 0.00815443 GADD45GIP growth arrest and DNA-damage-inducible,

1 gamma interacting protein 1 1.493655 0.02061236

GRN granulin 1.493607 0.03683456 IDUA iduronidase, alpha-L- 1.493505 0.00362299 olfactory receptor, family 11, subfamily H,

OR11H1 member 1 1.493333 0.02470052

EYA2 eyes absent homolog 2 (Drosophila) 1.492952 0.04100083 CCDC123 coiled-coil domain containing 123 1.492601 0.00411613 solute carrier family 35 (CMP-sialic acid

SLC35A1 transporter), member A 1 1.492421 0.03009839 SLC25A37 solute carrier family 25, member 37 1.492148 0.02969246 tumor necrosis factor receptor superfamily,

TNFRSF10B member 10b 1.492041 0.0473876

CUGBP2 CUG triplet repeat, R A binding protein 2 1.491452 0.00976238

FBX042 F-box protein 42 1.491338 0.03781683

WDYHV1 WDYHV motif containing 1 1.491315 0.0290555

TLR9 toll-like receptor 9 1.491057 0.02533605

STRN3 striatin, calmodulin binding protein 3 1.490937 0.04429151

JRKL jerky homolog-like (mouse) 1.490843 0.03773327

WDR65 WD repeat domain 65 1.489954 0.02181211 ubiquinol-cytochrome c reductase, Rieske

UQCRFS1 iron-sulfur polypeptide 1 1.489845 0.02452908 ASPN asporin 1.489751 0.02227567 L3MBTL2 l(3)mbt-like 2 (Drosophila) 1.489618 0.00853662 HESX1 HESX homeobox 1 1.48897 0.01313614 upstream transcription factor 2, c-fos

USF2 interacting 1.488893 0.02332004

RIT1 Ras-like without CAAX 1 1.488704 0.01691638

CXCR7 chemokine (C-X-C motif) receptor 7 1.48836 0.04469999 solute carrier family 3 (cystine, dibasic and

neutral amino acid transporters, activator of

cystine, dibasic and neutral amino acid

SLC3A1 transport), member 1 1.488117 0.00445729

CI lor© chromosome 11 open reading frame 9 1.487813 0.04541662

CSAD cysteine sulfinic acid decarboxylase 1.487784 0.04360266

N4BP2 NEDD4 binding protein 2 1.487665 0.04561429

BMPR1B bone morphogenetic protein receptor, type IB 1.487422 0.01325305

MY015B Myosin XVB pseudogene 1.487292 0.03221572

DEAD (Asp-Glu-Ala-Asp) box polypeptide

DDX20 20 1.487244 0.0038332 phosphatidylinositol-3,4,5-trisphosphate-

PREX2 dependent Rac exchange factor 2 1.486892 0.02762766

DBl/ 694375] 6.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

E2F6 E2F transcription factor 6 0.04873563 CCDC38 coiled-coil domain containing 38 0.04585151 C9 complement component 9 0.03138149 ILK integrin-linked kinase 0.03627245 AD54L RAD54-like (S. cerevisiae) 0.00858123

LAMB1 laminin, beta 1 0.00653142

CIB1 calcium and integrin binding 1 (calmyrin) 0.01107503

HIST1H2AC histone cluster 1 , H2ac 0.02826414

KIAA0319L KIAA0319-like 0.00321669

KIF5C kinesin family member 5C 0.03417717

GSK3A glycogen synthase kinase 3 alpha 0.01122827

KDM6A lysine (K)-specific demethylase 6A 0.02741398

GUSB glucuronidase, beta 0.00747287

QPCT glutaminyl-peptide cyclotransferase 0.04104095

BCAS4 breast carcinoma amplified sequence 4 0.02197508

BTN2A1 butyrophilin, subfamily 2, member Al 0.00038605

SYCP1 synaptonemal complex protein 1 0.04266731

KRBA1 KRAB-A domain containing 1 0.00220749 poly (ADP-ribose) polymerase family,

PARP4 member 4 0.00301927

SI 2 single-minded homolog 2 (Drosophila) 0.04804004

ATRNL1 attractin-like 1 0.03262769

SWI/SNF related, matrix associated, actin

dependent regulator of chromatin, subfamily

SMARCB1 b, member 1 0.0117909 ZZEF1 zinc finger, ZZ-type with EF-hand domain 1 0.02785441 pseudouridylate synthase 7 homolog (S.

PUS7 cerevisiae) 0.04277312

KDM4B lysine (K)-specific demethylase 4B 0.0292299

ZNF238 zinc finger protein 238 0.01726056 transglutaminase 3 (E polypeptide, protein-

TGM3 glutamine-gamma-glutamyltransferase) 0.02530872

ERGIC3 ERGIC and golgi 3 0.00847787

SLC41A3 solute carrier family 41, member 3 0.03315266 integrin, alpha 5 (fibronectin receptor, alpha

ITGA5 polypeptide) 0.01069824 NSBP1 Nucleosomal binding protein 1 0.03963054 NAV1 neuron navigator 1 0.0407588 FOSL2 FOS-like antigen 2 0.00031436 nuclear factor of kappa light polypeptide gene

NFKBID enhancer in B -cells inhibitor, delta 0.00732586

GGT1 gamma-glutamyltransferase 1 0.00264442

DOCK3 dedicator of cytokinesis 3 0.04456291

POU5F1 POU class 5 homeobox 1 0.0205725

ZNF776 zinc finger protein 776 0.01308106

PCTK3 PCTAIRE protein kinase 3 0.04215809 family with sequence similarity 171, member

FAM171B B 0.01422667 phosphoinositide-3 -kinase, regulatory subunit

PIK3R4 4 0.04851308

DB l/ 09437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

MED23 mediator complex subunit 23 0.04028339

LPIN2 lipin 2 0.04844938

PIAS2 protein inhibitor of activated STAT, 2 0.02186057

ZNF346 zinc finger protein 346 0.01112805

CCNL2 cyclin L2 0.02934899

ZNF317 Zinc finger protein 317 0.02908138

CUBN cubilin (intrinsic factor-cobalamin receptor) 0.03940218

ZNF669 zinc finger protein 669 0.008801 1

LRRC28 leucine rich repeat containing 28 0.04717917 signal transducer and activator of

STAT2 transcription 2, 113kDa 0.00464306

KATNAl katanin p60 (ATPase-containing) subunit A 1 0.03371068

KIAA1407 KIAA1407 0.04081785

PCID2 PCI domain containing 2 0.02600855

E 01LB EROl-like beta (S. cerevisiae) 0.02510508

HEATR7B2 HEAT repeat family member 7B2 0.0474

PTGR2 prostaglandin reductase 2 0.01576499

EP300 El A binding protein p300 0.03674569 sema domain, seven thrombospondin repeats

(type 1 and type 1-like), transmembrane

domain (TM) and short cytoplasmic domain,

SEMA5A (semaphorin) 5 A 0.03564324

TYSND1 trypsin domain containing 1 0.03841107

FASTKD1 FAST kinase domains 1 0.01426259 nucleotide-binding oligomerization domain

NOD2 containing 2 0.00327639 RNF167 ring finger protein 167 0.031 12976

DEAH (Asp-Glu-Ala-His) box polypeptide

DHX29 29 0.01019979 GSDMD gasdermin D 0.04369056

Microtubule-associated protein 1 light chain 3

MAP1LC3A alpha 0.04249948 TEAD3 TEA domain family member 3 0.03096314 family with sequence similarity 126, member

FAM126B B 0.03569178 LIPA lipase A, lysosomal acid, cholesterol esterase 0.02558128 advanced glycosylation end product-specific

AGER receptor 0.03465146 phytanoyl-CoA 2-hydroxylase interacting

PHYHIPL protein-like 0.02514305 solute carrier organic anion transporter

SLC04C1 family, member 4C 1 0.01184326

LDHD lactate dehydrogenase D 0.00975421

KRT28 keratin 28 0.01816292

IQ motif containing GTPase activating

IQGAP3 protein 3 0.01554435 nudix (nucleoside diphosphate linked moiety

NUDT3 X)-type motif 3 0.00899816 coiled-coil-helix-coiled-coil-helix domain

CHCHD2 containing 2 0.01172654 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P

value

ARHGAP9 Rho GTPase activating protein 9 1.466942 0.0280099

Family with sequence similarity 62 (C2

FAM62B domain containing) member B 1.466889 0.01377577

GCLC glutamate-cysteine ligase, catalytic subunit 1.466645 0.02679587

ARR3 arrestin 3, retinal (X-arrestin) 1.466048 0.01696652 regulator of G protein signaling 9 binding

RGS9BP protein 1.465883 0.03961413 phospholipase A2, group VI (cytosolic,

PLA2G6 calcium-independent) 1.465765 0.02742349

BAALC Brain and acute leukemia, cytoplasmic 1.46535 0.00024952

LRRN4 leucine rich repeat neuronal 4 1.465336 0.00738088

EXD3 exonuclease 3'-5' domain containing 3 1.464634 0.02526724 insulin-like growth factor 2 mRNA binding

IGF2BP2 protein 2 1.464327 0.04162595

FOXQ1 forkhead box Ql 1.464178 0.00212678 solute carrier family 39 (zinc transporter),

SLC39A13 member 13 1.464156 0.01844752

RASA2 RAS p21 protein activator 2 1.463718 0.00740884

KIF16B kinesin family member 16B 1.463596 0.011 15288

KRTAP10-8 keratin associated protein 10-8 1.463269 0.000559

CRTC2 CREB regulated transcription coactivator 2 1.463094 0.04358035 protein phosphatase, Mg2+/Mn2+ dependent,

PPM1H 1H 1.462605 0.01356042

S 100A16 S 100 calcium binding protein A 16 1.462571 0.04659033

TBL1X transducin (beta)-like lX-linked 1.462548 0.02846753

ZNF35 zinc finger protein 35 1.462328 0.01374461 peptidase domain containing associated with

PAMR1 muscle regeneration 1 1.461975 0.0389447

ADCY5 adenylate cyclase 5 1.461874 0.01746332

X-prolyl aminopeptidase (aminopeptidase P)

XPNPEP2 2, membrane-bound 1.461415 0.02555418 dual-specificity tyrosine-(Y)-phosphorylation

DYRK1A regulated kinase 1A 1.461295 0.02525277 cytochrome P450, family 3, subfamily A,

CYP3A7 polypeptide 7 1.461 141 0.03694454

MAPK14 mitogen-activated protein kinase 14 1.461055 0.00495656

NBEA neurobeachin 1.460973 0.03240274

C7orf42 chromosome 7 open reading frame 42 1.460876 0.02721132 semaphorin 7A, GPI membrane anchor (John

SEMA7A Milton Hagen blood group) 1.460443 0.04669342

RUNX1 runt-related transcription factor 1 1.46004 0.04954951

P1POX pipecolic acid oxidase 1.459566 0.01220641

COL16A1 collagen, type XVI, alpha 1 1.459324 0.00255753

CCDC155 coiled-coil domain containing 155 1.459029 0.00173523

ELSPBP1 epididymal sperm binding protein 1 1.458425 0.04218641

PRDM14 PR domain containing 14 1.458395 0.04902037 thyroid hormone receptor, beta (erythroblastic

leukemia viral (v-erb-a) oncogene homolog 2,

THRB avian) 1.457783 0.02863261

UHRF1BP1 UHRF1 binding protein 1 1.457743 0.04933297

Bl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

ATP synthase mitochondrial Fl complex

ATPAF2 assembly factor 2 0.04978588

UCK1 uridine-cytidine kinase 1 0.02615271

SPTBN2 spectrin, beta, non-erythrocytic 2 0.01348539 fumarylacetoacetate hydrolase

FAH (fumarylacetoacetase) 0.03082082 CCDC78 coiled-coil domain containing 78 0.00779009 protein kinase, AMP-activated, beta 1 non-

PRKAB1 catalytic subunit 1.456934 0.00674298

NADH dehydrogenase (ubiquinone) 1 alpha

NDUFA13 subcomplex, 13 0.04645714

KAT2A K(lysine) acetyltransferase 2A 0.00222147

RPL28 ribosomal protein L28 0.03220045 mannosyl (alpha-l,3-)-glycoprotein beta- 1,4-

MGAT4B N-acetylglucosaminyltransferase, isozyme B 0.04076649

FBN1 fibrillin 1 0.02322272

ULK4 unc- 1-like kinase 4 (C. elegans) 0.04272579

X-linked Kx blood group (McLeod

XK syndrome) 0.02239272

UPK2 uroplakin 2 0.04753193

CEP68 centrosomal protein 68kDa 0.03508992 platelet-derived growth factor receptor, alpha

PDGFRA polypeptide 0.0179518 USP51 Ubiquitin specific peptidase 51 0.03331138

Sema domain, seven thrombospondin repeats

(type 1 and type 1-like), transmembrane

domain (TM) and short cytoplasmic domain,

SEMA5B (semaphorin) 5B 1.454976 0.02313882 elongation factor Tu GTP binding domain

EFTUD2 containing 2 0.01886939

FR D4A FEPvM domain containing 4A 0.01579827

UHM 1 U2AF homology motif (UHM) kinase 1 0.03607354

DMXL2 Dmx-like 2 0.00874766

ZWI T ZW10 interactor 0.00942131

OSBP oxysterol binding protein 0.04350568

SBF2 SET binding factor 2 0.01078788

C12orf48 chromosome 12 open reading frame 48 0.02655996

SLC15A3 solute carrier family 15, member 3 0.0045492

CAPSL calcyphosine-like 0.02075975

FBXL17 F-box and leucine-rich repeat protein 17 0.03278551

C2orf53 chromosome 2 open reading frame 53 0.04970591

SRR serine racemase 0.03543625

EDN2 endothelin 2 0.03828423 cAMP responsive element binding protein 3-

CREB3L2 like 2 0.02761724 vacuolar protein sorting 33 homolog A (S.

VPS33A cerevisiae) 0.03534595 calmodulin regulated spectrin-associated

CAMS API protein 1 0.03807689 ADCY2 Adenylate cyclase 2 (brain) 0.02341994 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

1-aminocyclopropane-l -carboxylate synthase

ACCS homolog (Arabidopsis)(non-functional) 1.450606 0.0041161 1

SRM spermidine synthase 1.450314 0.0386075

KIF1B kinesin family member IB 1.450105 0.00795995

CLINT1 clathrin interactor 1 1.450089 0.03162318

HERC2P2 Hect domain and RLD 2 pseudogene 2 1.449895 0.03248465 protein phosphatase 1, regulatory (inhibitor)

PPP1R3D subunit 3D 1.449813 0.02244246

Plectin 1 , intermediate filament binding

PLEC1 protein 500kDa 1.449738 0.04213924

Clorf92 chromosome 1 open reading frame 92 1.44966 0.01543183

FLCN folliculin 1.449054 0.0230347

BRD7 bromodomain containing 7 1.448578 0.00933436 postmeiotic segregation increased 2-like 2

PMS2L2 pseudogene 1.448546 0.00505112

NCR1 natural cytotoxicity triggering receptor 1 1.448542 0.04855739

C10orfl04 Chromosome 10 open reading frame 104 1.448491 0.00267935

SSPN sarcospan (Kras oncogene-associated gene) 1.44845 0.03302467

RNA pseudouridylate synthase domain

RPUSD3 containing 3 1.448408 0.00998086

DRP2 dystrophin related protein 2 1.448236 0.00721484 latent transforming growth factor beta binding

LTBP2 protein 2 1.448086 0.02740361

TMEM14C transmembrane protein 14C 1.447908 0.01223887 aldehyde dehydrogenase 1 family, member

ALDH1L1 LI 1.447745 0.03397317

SMC IB structural maintenance of chromosomes IB 1.447653 0.01700052

CCDC45 coiled-coil domain containing 45 1.447508 0.01193568

FRMD6 FERM domain containing 6 1.447341 0.04706103

TRIM27 tripartite motif-containing 27 1.447185 0.04931 129

JMJD4 jumonji domain containing 4 1.446898 0.01389272

LEMD3 LEM domain containing 3 1.44673 0.04092375

ANXA6 annexin A6 1.446179 0.02394412

Olfactory receptor, family 2, subfamily W,

OR2W3 member 3 1.445748 0.02959812 tRNA methyltransferase 61 homolog B (S.

TRMT61B cerevisiae) 1.445655 0.04102036

C22orf24 chromosome 22 open reading frame 24 1.445618 0.04413586

SYCP2 synaptonemal complex protein 2 1.44557 0.01896128

UNC5C unc-5 homolog C (C. elegans) 1.445531 0.03566415

ADRBK1 adrenergic, beta, receptor kinase 1 1.445273 0.03231885 antagonist of mitotic exit network 1 homolog

AMN1 (S. cerevisiae) 1.445051 0.033402

RBPMS RNA binding protein with multiple splicing 1.44501 0.03858333

BMP6 bone morphogenetic protein 6 1.444856 0.02522336

IKZF4 IKAROS family zinc finger 4 (Eos) 1.444792 0.04121343

HEATR3 HEAT repeat containing 3 1.444721 0.0101094

LOXHD1 lipoxygenase homology domains 1 1.4447 0.00078933

DGKH Diacylglycerol kinase, eta 1.444408 0.0205564

KIAA1191 KIAA1191 1.444339 0.03985924 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

SPATA7 spermatogenesis associated 7 1.444215 0.01031062 transmembrane and tetratricopeptide repeat

TMTC4 containing 4 1.443929 0.02091397

SEC24C SEC24 family, member C (S. cerevisiae) 1.443774 0.03113679

LOC400940 hypothetical LOC400940 1.443742 0.04018813 sodium channel, voltage-gated, type XI, alpha

SCN11A subunit 1.44344 0.0435613 translocase of outer mitochondrial membrane

TOMM70A 70 homolog A (S. cerevisiae) 1.442531 0.03272251 toll-interleukin 1 receptor (TIR) domain

TIRAP containing adaptor protein 1.442305 0.0353389

MAML1 mastermind-like 1 (Drosophila) 1.442288 0.03228402 family with sequence similarity 115, member

FAM115C C 1.442232 0.03824025

SIGLEC9 sialic acid binding Ig-like lectin 9 1.442189 0.00149336

C15orf41 chromosome 15 open reading frame 41 1.442137 0.04387507

SMAD1 SMAD family member 1 1.442081 0.01612332

DMC1 dosage suppressor of mckl homolog,

meiosis-specific homologous recombination

DMC1 (yeast) 1.441914 0.01212361

SLC35B3 solute carrier family 35, member B3 1.441522 0.0071 1122

Cytochrome P450, family 2, subfamily C,

CYP2C19 polypeptide 19 1.441363 0.0170018

MOGAT3 monoacylglycerol O-acyltransferase 3 1.441283 0.03555083 mitochondrial carrier triple repeat 1

LOC494141 pseudogene 1.441004 0.01257991

UBXN10 UBX domain protein 10 1.440741 0.00806327

Clorf65 chromosome 1 open reading frame 65 1.440539 0.04575707

CRIP2 cysteine-rich protein 2 1.440525 0.03552207

CFB complement factor B 1.440334 0.02702825

C16orf45 chromosome 16 open reading frame 45 1.440058 0.01337094

CKLF chemokine-like factor 1.440038 0.04099922

MORN! MORN repeat containing 1 1.439966 0.04582123

KIAA0125 IAA0125 1.43966 0.04041667

GEMIN5 gem (nuclear organelle) associated protein 5 1.439594 0.0397608 tRNA splicing endonuclease 54 homolog (S.

TSEN54 cerevisiae) 1.439572 0.04851051

REPS1 RALBPl associated Eps domain containing 1 1.439539 0.0313097

CSMD2 CUB and Sushi multiple domains 2 1.439487 0.00017482 eukaryotic translation elongation factor 1

EEF1A1 alpha 1 1.439448 0.03794699

MCHR1 melanin-concentrating hormone receptor 1 1.439291 0.00549179

NKX3-1 NK3 homeobox 1 1.439246 0.00916252 protein C (inactivator of coagulation factors

PROC Va and Villa) 1.439197 0.03744441

14-Sep N/A 1.439028 0.02172227

Neural precursor cell expressed,

NEDD4L developmentally down-regulated 4-like 1.438929 0.03498104 protein phosphatase 1 , regulatory (inhibitor)

PPP1R14D subunit 14D 1.438585 0.03281531

⁾B 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upreguiated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P

Change value

solute carrier family 12

(sodium/potassium/chloride transporters),

SLC12A1 member 1 1.438116 0.02379177

PSG2 pregnancy specific beta- 1 -glycoprotein 2 1.437935 0.04206079

DPT dermatopontin 1.437896 0.04729978

ARMC9 armadillo repeat containing 9 1.437839 0.02857529

EPAS1 endothelial PAS domain protein 1 1.437838 0.02537747

ATL1 atlastin GTPase 1 1.437797 0.02539355

ZNF419 Zinc finger protein 419 1.437381 0.03921324

TRNT1 tRNA nucleotidyl transferase, CCA-adding, 1 1.436917 0.01566898

RNASEH2C ribonuclease H2, subunit C 1.436884 0.04326723

UBXN1 UBX domain protein 1 1.436743 0.01261269

AHCY adenosylhomocysteinase 1.436738 0.0251681

CI orf51 chromosome 1 open reading frame 51 1.43641 0.0452643

DTL denticleless homolog (Drosophila) 1.436258 0.00228503

SPAG7 sperm associated antigen 7 1.435961 0.02176801 nuclear receptor subfamily 1, group H,

NR1H4 member 4 1.43593 0.01391427

CLASP 1 cytoplasmic linker associated protein 1 1.435908 0.02537964

DDHD1 DDHD domain containing 1 1.435652 0.02093535

KIF1A kinesin family member 1A 1.435186 0.04232803

DFNB31 Deafness, autosomal recessive 31 1.434434 0.0130253 kinase non-catalytic C-lobe domain (KIND)

KNDC1 containing 1 1.43423 0.04860364

SMOC1 SPARC related modular calcium binding 1 1.434133 0.01865818 roundabout homolog 4, magic roundabout

ROB04 (Drosophila) 1.433999 0.0402941

WDR68 WD repeat domain 68 1.433988 0.01943028

KRT6B keratin 6B 1.433946 0.04035729

CTPS2 CTP synthase II 1.433712 0.00451117

Arginyl aminopeptidase (aminopeptidase B)-

RNPEPL1 like 1 1.433653 0.0127466

RPL23A ribosomal protein L23a 1.433396 0.03929183

PI4KA phosphatidylinositol 4-kinase, catalytic, alpha 1.433153 0.01035201

ADRBK2 adrenergic, beta, receptor kinase 2 1.432822 0.03410394

LOC1001304 similar to PI gene for c subunit of human

92 mitochondrial ATP synthase 1.432758 0.02573644

G-protein signaling modulator 1 (AGS3-like,

GPSM1 C. elegans) 1.432471 0.01972055

SCRIB scribbled homolog (Drosophila) 1.431988 0.04023653

WFDC1 WAP four-disulfide core domain 1 1.431673 0.01610888

LMAN1L Lectin, mannose-binding, 1 like 1.431654 0.04178231

6-phosphofructo-2-kinase/fructose-2,6-

PF FB3 biphosphatase 3 1.431618 0.04427076 gamma-aminobutyric acid (GABA) B

GABBR2 receptor, 2 1.431377 0.01905578

TRM5 tRNA methyltransferase 5 homolog

TRMT5 (S. cerevisiae) 1.431236 0.01264871

SYT15 synaptotagmin XV 1.431127 0.0468319

RBM6 RNA binding motif protein 6 1.43099 0.0074634

DB1/ 69437516.1 Supplemental Table 1. Gene Transcripts Up regulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value complement component 4A (Rodgers blood

C4A group) 1.430559 0.01 175462

ATP -binding cassette, sub-family B

ABCB1 (MDR/TAP), member 1 1.430367 0.02609242

ZNF174 zinc finger protein 174 1.430263 0.02382622

ASAM adipocyte-specific adhesion molecule 1.429698 0.01575073

SULF2 sulfatase 2 1.429509 0.03707728

PCSK1 proprotein convertase subtilisin/kexin type 1 1.429504 0.00675947

DEXI Dexi homolog (mouse) 1.4295 0.00979015

CREB5 cAMP responsive element binding protein 5 1.429176 0.03559724

ITK IL2-inducible T-cell kinase 1.429076 0.04169545

PGAP1 post-GPI attachment to proteins 1 1.429043 0.02809428 cadherin, EGF LAG seven-pass G-type

CELSR1 receptor 1 (flamingo homolog, Drosophila) 1.428928 0.01308152 FOXM1 forkhead box Ml 1.428823 0.00664337 sialic acid binding Ig-like lectin 1 ,

SIGLECl sialoadhesin 1.428823 0.03063211

DTX2 deltex homolog 2 (Drosophila) 1.428784 0.01838192

PRRT1 proline-rich transmembrane protein 1 1.428698 0.00624586

C14orfl33 Chromosome 14 open reading frame 133 1.428084 0.01192022

GRM5 glutamate receptor, metabotropic 5 1.428 0.00569792 general transcription factor IIF, polypeptide 2,

GTF2F2 30kDa 1.427729 0.03320271 XRRA1 X-ray radiation resistance associated 1 1.42764 0.02680118 sodium channel, voltage-gated, type V, alpha

SCN5A subunit 1.427595 0.04117775 YST2 MYST histone acetyltransferase 2 1.427383 0.0315683

FZD5 frizzled homolog 5 (Drosophila) 1.427287 0.00237956

SYNE2 spectrin repeat containing, nuclear envelope 2 1.427261 0.02730996

ZNF787 zinc finger protein 787 1.427139 0.04991913 gamma-aminobutyric acid (GABA) A

GABRD receptor, delta 1.426991 0.00917325

OPRLl opiate receptor-like 1 1.426883 0.00697309

FZD6 frizzled homolog 6 (Drosophila) 1.426781 0.02987967

KRTAP21-2 keratin associated protein 21-2 1.426314 0.01330069 TMEM63A transmembrane protein 63A 1.426248 0.02568617 leukocyte immunoglobulin-like receptor,

subfamily B (with TM and ITIM domains),

LILRB1 member 1 1.425524 0.04811093 solute carrier family 24

(sodium/potassium/calcium exchanger),

SLC24A6 member 6 1.425131 0.00428639

MY05B myosin VB 1.424893 0.04053217

UBE2Z ubiquitin-conjugating enzyme E2Z 1.424388 0.04566522 major facilitator super family domain

MFSD3 containing 3 1.424253 0.03529744 ankyrin repeat, SAM and basic leucine zipper

ASZ1 domain containing 1 1.423832 0.00549437

MORC3 MORC family CW-type zinc finger 3 1.423767 0.0282166

COQ6 coenzyme Q6 homolog, monooxygenase (S. 1.423745 0.01763509

DB1/ 69437₅16.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value cerevisiae)

ITGB4 integrin, beta 4 1.423742 0.00487711

SRP54 signal recognition particle 54kDa 1.423741 0.02741312

VPRBP Vpr (HIV-1) binding protein 1.423671 0.01590628

SCRN3 secernin 3 1.423637 0.00924737

TMEM196 transmembrane protein 196 1.423504 0.03912515

PAX4 paired box 4 1.4234 0.03546965

H3F3B H3 histone, family 3B (H3.3B) 1.423228 0.0202904

LYNX1 Ly6/neurotoxin 1 1.423037 0.0006764

IL21R interleukin 21 receptor 1.42299 0.0210596

VAC 14 Vac 14 homolog (S. cerevisiae) 1.422842 0.03352068

Purinergic receptor P2Y, G-protein coupled,

P2RY12 12 1.42284 0.03032864 solute carrier family 39 (zinc transporter),

SLC39A7 member 7 1.422776 0.00564315

RAB11FIP5 RAB11 family interacting protein 5 (class I) 1.422343 0.02262736 polyamine modulated factor 1 binding protein

PMFBP1 1 1.422189 0.04357855

GPR115 G protein-coupled receptor 115 1.422028 0.03195424

RRAGB Ras-related GTP binding B 1.421971 0.04892957

MNX1 motor neuron and pancreas homeobox 1 1.421965 0.02578174

CCDC27 coiled-coil domain containing 27 1.421938 0.00474015 low density lipoprotein receptor-related

LRP1B protein IB 1.421678 0.00833432

INPP5E inositol polyphosphate-5 -phosphatase, 72 kDa 1.421631 0.00536565 vacuolar protein sorting 53 homolog (S.

VPS53 cerevisiae) 1.421566 0.04694093

TIMP4 TIMP metallopeptidase inhibitor 4 1.421302 0.00096167 procollagen-lysine 1, 2-oxoglutarate 5-

PLOD1 dioxygenase 1 1.421203 0.03569493

DKFZp451A2

11 DKFZp451A211 protein 1.421088 0.04583309

C4orf29 chromosome 4 open reading frame 29 1.421085 0.03705249 pleckstrin homology domain containing,

PLEKHB1 family B (evectins) member 1 1.420822 0.00910407

XAGEIA X antigen family, member 1 A 1.420684 0.00468609 ring finger and CHY zinc finger domain

RCHY1 containing 1 1.420477 0.00583725

FGL2 fibrinogen-like 2 1.419858 0.02205817

DOCK6 dedicator of cytokinesis 6 1.419724 0.00615545

GIGYF2 GRB10 interacting GYF protein 2 1.419681 0.04428945 degenerative spermatocyte homolog 1 , lipid

DEGS1 desaturase (Drosophila) 1.419499 0.017395

Bactericidal/permeability-increasing protein¬

BPIL2 like 2 1.419455 0.02723426

LPHN3 latrophilin 3 1.419388 0.04837424

TMEM67 transmembrane protein 67 1.419169 0.04411419 ectonucleoside triphosphate

ENTPD5 diphosphohydrolase 5 1.419164 0.02048402

CEP72 centrosomal protein 72kDa 1.419136 0.02292996

)B1/ 09437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

AMOTL1 angiomotin like 1 1.418766 0.01087323

ATPase, Ca++ transporting, plasma

ATP2B2 membrane 2 1.418552 0.04957391

VGLL4 vestigial like 4 (Drosophila) 1.41834 0.04794193 solute carrier family 37 (glycerol-3-phosphate

SLC37A3 transporter), member 3 1.41767 0.0252969

ZNF658 zinc finger protein 658 1.417326 0.01854368

FTSJD2 FtsJ methyltransferase domain containing 2 1.417106 0.04306268

ADIPOR1 adiponectin receptor 1 1.417013 0.02325571

ArfGAP with RhoGAP domain, ankyrin

ARAP1 repeat and PH domain 1 1.41686 0.01952002

KDM4C lysine (K)-specific demethylase 4C 1.416713 0.01518097

MRPL48 mitochondrial ribosomal protein L48 1.416469 0.03672311

BOLA3 bolA homolog 3 (E. coli) 1.416326 0.04327928

VGF VGF nerve growth factor inducible 1.416295 0.01054276

NRAP nebulin-related anchoring protein 1.416244 0.03451808

ABHD11 abhydrolase domain containing 11 1.416205 0.04257664 cutA divalent cation tolerance homolog (E.

CUTA coli) 1.41605 0.00410166

OTUB2 OTU domain, ubiquitin aldehyde binding 2 1.415713 0.0037679 rabaptin, RAB GTPase binding effector

RABEP2 protein 2 1.415527 0.01931713

EXOC2 exocyst complex component 2 1.41514 0.00306119

C5orf44 chromosome 5 open reading frame 44 1.415138 0.00720595

ENGASE endo-beta-N-acetylglucosaminidase 1.414899 0.01551833

HSD17B7 hydroxysteroid (17-beta) dehydrogenase 7 1.414871 0.02314324 family with sequence similarity 59, member

FAM59A A 1.414685 0.01858809

ATP -binding cassette, sub-family A (ABCl),

ABCA5 member 5 1.414504 0.01366697

ADPRHL1 ADP-ribosylhydrolase like 1 1.41442 0.04904569

TCEAL2 transcription elongation factor A (Sll)-like 2 1.414201 0.02452442 phosphodiesterase 4D, cAMP-specific

(phosphodiesterase E3 dunce homolog,

PDE4D Drosophila) 1.414178 0.0113491

TUBE1 tubulin, epsilon 1 1.414105 0.00144696

MYOCD myocardin 1.414081 0.04496923

CKMT2 creatine kinase, mitochondrial 2 (sarcomeric) 1.414046 0.0128032

CYFIP2 cytoplasmic FMR1 interacting protein 2 1.413943 0.01863851

CUZD1 CUB and zona pellucida-like domains 1 1.413924 0.00851985

FM03 flavin containing monooxygenase 3 1.4139 0.02493988

ABLIM1 actin binding LIM protein 1 1.413544 0.04823307 tankyrase, TRF1 -interacting ankyrin-related

TNKS2 ADP-ribose polymerase 2 1.413046 0.03105238

CPNE1 copine I 1.412965 0.00879491

BTBD7 BTB (POZ) domain containing 7 1.412938 0.0451493 protein phosphatase, EF-hand calcium

PPEF2 binding domain 2 1.412887 0.01372869

TMEM45B transmembrane protein 45B 1.412854 0.02498117

NECAB2 N-terminal EF-hand calcium binding protein 1.412734 0.00482513

DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P

Change value

2

signal-induced proliferation-associated 1 like

SIPA1L1 1 1.412649 0.03131075

TTC13 tetratricopeptide repeat domain 13 1.412549 0.02575639 epithelial cell transforming sequence 2

ECT2 oncogene 1.412257 0.00609004 mitogen-activated protein kinase kinase

MAP3K5 kinase 5 1.412219 0.0127853

IL17RC interleukin 17 receptor C 1.412013 0.01 14419 ectonucleotide

ENPP6 pyrophosphatase/phosphodiesterase 6 1.411987 0.02580456 menage a trois homolog 1, cyclin H assembly

MNAT1 factor (Xenopus laevis) 1.411922 0.02407525

CLCA3P chloride channel accessory 3 (pseudogene) 1.411853 0.04263647 calcium channel, voltage-dependent, beta 2

CACNB2 subunit 1.411807 0.0276152

CASC5 cancer susceptibility candidate 5 1.411558 0.00946303

HK1 hexokinase 1 1.411 14 0.04448314

CALR calreticulin 1.411 0.04006515

C8orf38 chromosome 8 open reading frame 38 1.410974 0.02540992

FLJ45950 FLJ45950 protein 1.410895 0.03436742 inositol polyphosphate-4-phosphatase, type II,

I PP4B 105kDa 1.41084 0.03007155

C5orf24 chromosome 5 open reading frame 24 1.41066 0.02510297

LY6H lymphocyte antigen 6 complex, locus H 1.410606 0.0133544

PTH1R parathyroid hormone 1 receptor 1.410543 0.00783519 intraflagellar transport 57 homolog

IFT57 (Chlamydomonas) 1.410484 0.02169174

DY C112 dynein, cytoplasmic 1 , intermediate chain 2 1.410334 0.0279939 pregnancy specific beta- 1 -glycoprotein 7

PSG7 (gene/pseudogene) 1.410282 0.03956582

FGFRL1 fibroblast growth factor receptor-like 1 1.410036 0.04769822

DAO D-amino-acid oxidase 1.409682 0.01256402

SULF1 sulfatase 1 1.409417 0.02525754 protein phosphatase 2, regulatory subunit B',

PPP2R5D delta 1.409369 0.02720365

ECHDC2 enoyl CoA hydratase domain containing 2 1.409332 0.0282362 cylicin, basic protein of sperm head

CYLC2 cytoskeleton 2 1.409008 0.03520158

C3orf20 chromosome 3 open reading frame 20 1.408985 0.01768384

TKTL1 transketolase-like 1 1.408946 0.01008055

C5orf26 Chromosome 5 open reading frame 26 1.408597 0.00536435

FNDC4 fibronectin type III domain containing 4 1.408025 0.02248347 superkiller viralicidic activity 2-like (S.

SKIV2L cerevisiae) 1.407726 0.00726796

DVL1 dishevelled, dsh homolog 1 (Drosophila) 1.407381 0.01421061

SRD5A3 steroid 5 alpha-reductase 3 1.407294 0.04982272

GPR98 G protein-coupled receptor 98 1.407268 0.01027858

NLGN1 neuroligin 1 1.407195 0.01186509

UQCRC1 ubiquinol-cytochrome c reductase core 1.407184 0.01608345

DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value protein I

OSBPL9 Oxysterol binding protein-like 9 1.406858 0.02191181

UBTD2 ubiquitin domain containing 2 1.406757 0.02310731

TARSL2 threonyl-tRNA synthetase-like 2 1.406743 0.03616151

DPF2 D4, zinc and double PHD fingers family 2 1.406662 0.00964088 asparagine-linked glycosylation 9, alpha- 1,2-

ALG9 mannosyltransferase homo log (S. cerevisiae) 1.406114 0.02876208

MXD4 MAX dimerization protein 4 1.406008 0.0335339

ZNF517 zinc finger protein 517 1.405979 0.0127863

C13orf31 chromosome 13 open reading frame 31 1.405851 0.02596859

JTV1 JTV1 gene 1.405782 0.00950045

SASH1 SAM and SH3 domain containing 1 1.404986 0.01632024 solute carrier family 6 (neurotransmitter

SLC6A8 transporter, creatine), member 8 1.404866 0.03216539

H2AFV H2A histone family, member V 1.40403 0.03700618

CUL7 cullin 7 1.403988 0.01660501

ST7 suppression of tumorigenicity 7 1.403839 0.01748328

RP1L1 retinitis pigmentosa 1 -like 1 1.40353 0.03560601

La ribonucleoprotein domain family, member

LARP4 4 1.403388 0.02344304 sodium channel, voltage-gated, type IV, alpha

SCN4A subunit 1.402997 0.00767131

DOK6 docking protein 6 1.402978 0.04549792 nucleolar complex associated 3 homolog (S.

NOC3L cerevisiae) 1.402952 0.03708411

NECAP2 NECAP endocytosis associated 2 1.402829 0.032084

LMCD1 LIM and cysteine-rich domains 1 1.402766 0.03712631

N-deacetylase/N-sulfotransferase (heparan

NDST1 glucosaminyl) 1 1.402735 0.03263743

TBCKL N/A 1.402699 0.03188772

ZNF770 zinc finger protein 770 1.402633 0.00386837 IAA1797 KIAA1797 1.402343 0.00803293

CENPC1 centromere protein C 1 1.402049 0.0016592

WEE1 WEE1 homolog (S. pombe) 1.401628 0.01546795

GLT25D1 glycosyltransferase 25 domain containing 1 1.401591 0.0059023

COL1A2 collagen, type I, alpha 2 1.401494 0.03357532

SH3BP5L SH3 -binding domain protein 5 -like 1.401407 0.0460964

GRRPl glycine/arginine rich protein 1 1.400911 0.02169507

FBXL18 F-box and leucine-rich repeat protein 18 1.400868 0.03213365

TMEM5 transmembrane protein 5 1.400644 0.02448413

PRKCD protein kinase C, delta 1.400535 0.00850696

MEIS1 Meis homeobox 1 1.400454 0.04054264 nuclear factor of kappa light polypeptide gene

NFKBIL1 enhancer in B-cells inhibitor-like 1 1.400366 0.02647057

SLC35A5 solute carrier family 35, member A5 1.400233 0.00237093 solute carrier family 36 (proton/amino acid

SLC36A1 symporter), member 1 1.399675 0.02076631

ANXA2P1 annexin A2 pseudogene 1 1.399533 0.02940857

ANKRD5 ankyrin repeat domain 5 1.399432 0.0007459

PARVG parvin, gamma 1.399324 0.00164838

DB1/ 6943751₆.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value mitogen-activated protein kinase kinase

MAP4K5 kinase kinase 5 1.399107 0.02479176

ZNF100 Zinc finger protein 100 1.398985 0.00625826

CATSPER2 cation channel, sperm associated 2 1.398976 0.00496629

C6orfl05 chromosome 6 open reading frame 05 1.398805 0.04529836 serum/glucocorticoid regulated kinase family,

SG 3 member 3 1.398376 0.04615825

Protein tyrosine phosphatase, non-receptor

PTPN5 type 5 (striatum-enriched) 1.398369 0.00577337

TNKS1BP1 tankyrase 1 binding protein 1, 182kDa 1.398288 0.00506839

DENND5A DENN/MADD domain containing 5A 1.398194 0.0134378

SMAD5 SMAD family member 5 1.397969 0.04112916

GPR85 G protein-coupled receptor 85 1.397847 0.01995992 retinol dehydrogenase 11 (all-trans/9-cis/l 1-

RDH11 cis) 1.397657 0.0050891

ZNF92 Zinc finger protein 92 1.397295 0.01910671

C6orfl23 Chromosome 6 open reading frame 123 1.397278 0.01660509

TULP4 tubby like protein 4 1.397015 0.02174879

GAS2L2 growth arrest-specific 2 like 2 1.396857 0.00769112

MON2 MON2 homolog (S. cerevisiae) 1.396562 0.02277165

NCKAP1L NCK-associated protein 1 -like 1.396475 0.03478304

RAB28 RAB28, member RAS oncogene family 1.396447 0.02485702

WASH2P WAS protein family homolog 2 pseudogene 1.396235 0.01601012

C2orf43 chromosome 2 open reading frame 43 1.396214 0.03663188

ZFHX4 zinc finger homeobox 4 1.395673 0.03745583 killer cell immunoglobulin-like receptor, two

KIR2DL4 domains, long cytoplasmic tail, 4 1.395657 0.03599348

IKZF2 IKAROS family zinc finger 2 (Helios) 1.395479 0.03064697

Olfactory receptor, family 2, subfamily H,

OR2H2 member 2 1.395417 0.04713191 olfactory receptor, family 2, subfamily B,

OR2B2 member 2 1.395263 0.00597808 PTN kaptin (actin binding protein) 1.395175 0.00347347

LOC1001343

96 similar to zinc finger protein 799 1.39516 0.04812719

CDH2 cadherin 2, type 1, N-cadherin (neuronal) 1.395061 0.04529743 translocase of inner mitochondrial membrane

TIMM44 44 homolog (yeast) 1.394702 0.02292879

ATP-binding cassette, sub-family F (GCN20),

ABCF2 member 2 1.394627 0.03672061

ZNF193 zinc finger protein 193 1.393586 0.00256927

MOSPD2 motile sperm domain containing 2 1.393409 0.00750667

AMELX amelogenin, X-linked 1.393182 0.01706607

C20orfl49 Chromosome 20 open reading frame 149 1.392992 0.03940517

BLM Bloom syndrome, RecQ helicase-like 1.392962 0.02331052

PRMT8 protein arginine methyltransferase 8 1.392528 0.04848671

FOXP1 forkhead box PI 1.392398 0.03455442

ATP-binding cassette, sub-family G

ABCG4 (WHITE), member 4 1.392177 0.02679048

ST13 suppression of tumorigenicity 13 (colon 1.392146 0.02567641 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value carcinoma) (Hsp70 interacting protein)

GTF2A1L general transcription factor IIA, 1 -like 1.392143 0.0445689

Clorf25 chromosome 1 open reading frame 25 1.391853 0.00399888

BBS2 Bardet-Biedl syndrome 2 1.391766 0.0482488 solute carrier family 34 (sodium phosphate),

SLC34A2 member 2 1.391721 0.00394565

PPIA peptidylprolyl isomerase A (cyclophilin A) 1.391479 0.00135116 secreted protein, acidic, cysteine-rich

SPARC (osteonectin) 1.391088 0.04346937

LIMD1 LIM domains containing 1 1.390887 0.01945038

BAG2 BCL2-associated athanogene 2 1.390864 0.00399346

CNDP dipeptidase 2 (metallopeptidase M20

CNDP2 family) 1.39074 0.04661699

SGK2 serum/glucocorticoid regulated kinase 2 1.39068 0.03191632

PDE3A phosphodiesterase 3A, cGMP -inhibited 1.390545 0.04174219

FNDC7 fibronectin type III domain containing 7 1.390462 0.0021826

FLNC filamin C, gamma 1.390381 0.00718939 alcohol dehydrogenase 4 (class II), pi

ADH4 polypeptide 1.390243 0.02064603

C6orfl0 chromosome 6 open reading frame 10 1.389954 0.0360883

ST6 beta-galactosamide alpha-2,6-

ST6GAL1 sialyltranferase 1 1.389745 0.03513611

HELQ helicase, POLQ-like 1.389705 0.03292837

GGCX gamma-glutamyl carboxylase 1.38939 0.0460239

PI15 peptidase inhibitor 15 1.389099 0.02507614 nuclear receptor subfamily 1, group I,

NR1I2 member 2 1.388937 0.00647909

PGPEP1 Pyroglutamyl-peptidase I 1.388913 0.00818542 family with sequence similarity 174, member

FAM174B B 1.388897 0.0283348

PYCARD PYD and CARD domain containing 1.388828 0.02722781

SLC38A4 solute carrier family 38, member 4 1.388811 0.04897691

CENPP centromere protein P 1.388721 0.02320842

FCRL5 Fc receptor-like 5 1.388699 0.01992709

TM7SF3 transmembrane 7 superfamily member 3 1.388536 0.01990459

SLPI secretory leukocyte peptidase inhibitor 1.38852 0.04288421

SORT1 sortilin 1 1.388421 0.00563762

SIPA1 signal-induced proliferation-associated 1 1.388256 0.00350995

RAD52 RAD52 homolog (S. cerevisiae) 1.388195 0.01704318 sodium channel, voltage-gated, type III, alpha

SCN3A subunit 1.387952 0.03410646

Cl lorfl6 chromosome 11 open reading frame 16 1.387896 0.01527868

KDELC2 KDEL (Lys-Asp-Glu-Leu) containing 2 1.387517 0.03464133

SYTL4 synaptotagmin-like 4 1.3871 18 0.02970297

POTEA POTE ankyrin domain family, member A 1.387003 0.04607794

C4orf8 Chromosome 4 open reading frame 8 1.386989 0.03542979

LTA4H leukotriene A4 hydrolase 1.386545 0.03548382

C14orfl77 chromosome 14 open reading frame 177 1.386309 0.00984611

GBP4 guanylate binding protein 4 1.386077 0.04580035

RRP9 ribosomal RNA processing 9, small subunit 1.386013 0.00671923

DB1/ 6943751₆.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

(SSU) processome component, homolog

(yeast)

SIK2 salt-inducible kinase 2 0.04197294

NKD1 naked cuticle homolog 1 (Drosophila) 0.03408552

UBE3B ubiquitin protein ligase E3B 0.04875568

RYR1 ryanodine receptor 1 (skeletal) 0.02386302

MAK male germ cell-associated kinase 0.04875467

Ras protein-specific guanine nucleotide-

RASGRF1 releasing factor 1 0.04400616

ULK3 unc-51-like kinase 3 (C. elegans) 0.04520021

NKTR natural killer-tumor recognition sequence 0.03433816

C5orf51 chromosome 5 open reading frame 51 0.01685538

MYCBP2 MYC binding protein 2 0.02599111

MEX3B mex-3 homolog B (C. elegans) 0.01461286 family with sequence similarity 50, member

FAM50A A 0.02964922 NVL nuclear VCP-like 0.02522613 CD96 CD96 molecule 0.00301321 Cl lorGO chromosome 11 open reading frame 30 0.01287423

ST6 (alpha-N-acetyl-neuraminyl-2,3 -beta-

ST6GALNAC galactosyl-l,3)-N-acetylgalactosaminide

3 alpha-2,6-sialyltransferase 3 0.01459722

CD99L2 CD99 molecule-like 2 0.02914173

ALAD aminolevulinate dehydratase 0.04249311

FLU Friend leukemia virus integration 1 0.04745503 kelch repeat and BTB (POZ) domain

BTBD2 containing 2 0.02264339 myosin, light chain 12A, regulatory, non-

MYL12A sarcomeric 0.01246539 v-erb-a erythroblastic leukemia viral

ERBB4 oncogene homolog 4 (avian) 0.02315776 KPNA3 karyopherin alpha 3 (importin alpha 4) 0.0289694

WW domain binding protein 4 (formin

WBP4 binding protein 21) 0.04909614

KIF13B kinesin family member 13B 0.04347903

SPOCD1 SPOC domain containing 1 0.02601498 sarcoglycan, alpha (50kDa dystrophin-

SGCA associated glycoprotein) 0.00441295 SNX19 Sorting nexin 19 0.03833771 solute carrier family 12 (potassium/chloride

SLC12A6 transporters), member 6 0.02817791 CAMTA1 calmodulin binding transcription activator 1 0.04779083 EFHD2 EF-hand domain family, member D2 0.01067716 MDM4 Mdm4 p53 binding protein homolog (mouse) 0.04659048 amyloid beta (A4) precursor protein-binding,

APBB3 family B, member 3 0.03664956 GPR135 G protein-coupled receptor 135 0.04040497 mitochondrial rRNA methyltransferase 1

MRM1 homolog (S. cerevisiae) 0.0007521 HTRA2 HtrA serine peptidase 2 0.04940812

DB1/ 69437₅16.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

KIRREL3 kin of IRRE like 3 (Drosophila) 1.381017 0.00737628 syntrophin, beta 2 (dystrophin-associated

SNTB2 protein Al, 59kDa, basic component 2) 1.380994 0.02123007

M S1 Meckel syndrome, type 1 1.380991 0.04213353

HERC6 hect domain and RLD 6 1.380985 0.01442056

CPLX2 complexin 2 1.380866 0.04521856

IP6K3 inositol hexakisphosphate kinase 3 1.38025 0.00952223

PDZRN3 PDZ domain containing ring finger 3 1.380245 0.00918114

AQP6 aquaporin 6, kidney specific 1.379963 0.03940188

USP8 ubiquitin specific peptidase 8 1.379749 0.01506322

CCDC93 coiled-coil domain containing 93 1.379414 0.03060352 leukocyte immunoglobulin-like receptor,

LILRA3 subfamily A (without TM domain), member 3 1.37924 0.04854274

PI-3-kinase-related kinase SMG-1

LOC595101 pseudogene 1.379113 0.03181381

FGFR4 fibroblast growth factor receptor 4 1.379071 0.02539936

ZNF16 zinc finger protein 16 1.37864 0.02760601

MTSS1 metastasis suppressor 1 1.378356 0.01047276

RNFT2 ring finger protein, transmembrane 2 1.37832 0.01084488

PIPSL PIP5K1 A and PSMD4-like 1.37826 0.03426384

ZNF597 zinc finger protein 597 1.378182 0.01974716

PH domain and leucine rich repeat protein

PHLPP phosphatase 1.378024 0.03544604 nuclear factor related to kappaB binding

NFRKB protein 1.377916 0.00803175

UTP6, small subunit (SSU) processome

UTP6 component, homolog (yeast) 1.377461 0.04338852

GIMAP5 GTPase, IMAP family member 5 1.377391 0.00262894 ribosomal protein S6 kinase, 90kDa,

RPS6KA2 polypeptide 2 1.377333 0.03489272

PRKCB protein kinase C, beta 1.377304 0.0430421 zinc finger, RAN-binding domain containing

ZRANB3 3 1.377256 0.02630989

GPR133 G protein-coupled receptor 133 1.377234 0.02937482

DEAD (Asp-Glu-Ala-Asp) box polypeptide

DDX60 60 1.377194 0.01933972

UDP-N-acetyl-alpha-D- galactosamine.'polypeptide N- acetylgalactosaminyltransferase 11 (GalNAc-

GALNT11 Tl l) 1.37695 0.04489588

FOXD1 forkhead box Dl 1.376873 0.00527696

PTDSS1 phosphatidylserine synthase 1 1.376364 0.01628131

COL12A1 collagen, type XII, alpha 1 1.376147 0.04737272

CALB1 calbindin 1, 28kDa 1.37604 0.02319277

F9 coagulation factor IX 1.375946 0.04016998

TNXA tenascin XA pseudogene 1.375903 0.02711531

CD8A CD8a molecule 1.375754 0.01878319

NGFI-A binding protein 1 (EGR1 binding

NAB1 protein 1) 1.375422 0.02338057

FERMT3 fermitin family homolog 3 (Drosophila) 1.375379 0.03007465

⁾B 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

ZNF394 Zinc finger protein 394 1.375341 0.0292037

DNAH10 Dynein, axonemal, heavy chain 10 1.375307 0.02636417

USP38 ubiquitin specific peptidase 38 1.37522 0.04727816

PH G1 phosphorylase kinase, gamma 1 (muscle) 1.37485 0.03284559

YY1AP1 YY1 associated protein 1 1.374742 0.02095981 inositol polyphosphate-5 -phosphatase,

I PP5D 145kDa 1.374524 0.00364048

CLSTN2 calsyntenin 2 1.374429 0.00355959

ECM1 extracellular matrix protein 1 1.374408 0.0430531

USP25 ubiquitin specific peptidase 25 1.374384 0.01432184

CHKA choline kinase alpha 1.374342 0.02812555

Rho guanine nucleotide exchange factor

ARHGEF10L (GEF) 10-like 1.374329 0.04034993

WDR6 WD repeat domain 6 1.374259 0.04345138

TFCP2 transcription factor CP2 1.373815 0.0381982

PMS2L11 N/A 1.373707 0.01103585

KDELC1 KDEL (Lys-Asp-Glu-Leu) containing 1 1.37365 0.0092781

MEDI O mediator complex subunit 10 1.373572 0.01287145 family with sequence similarity 135, member

FAM135A A 1.373455 0.03341903

BCL2L1 BCL2-like 1 1.373446 0.02246357

ADAM metallopeptidase with

ADAMTS2 thrombospondin type 1 motif, 2 1.373402 0.03624825

CLCN7 chloride channel 7 1.373344 0.03694279

C3orf23 chromosome 3 open reading frame 23 1.373321 0.03609232 phospholipase Dl, phosphatidylcholine-

PLD1 specific 1.373202 0.04783635 cytidine monophosphate (UMP-CMP) kinase

CMPK2 2, mitochondrial 1.373034 0.04652844 membrane protein, palmitoylated 5 (MAGUK

MPP5 p55 subfamily member 5) 1.372794 0.01412992

C21orf67 chromosome 21 open reading frame 67 1.372758 0.03063945

H0XC8 homeobox C8 1.372535 0.03904603

PSTK phosphoseryl-tRNA kinase 1.372512 0.0045338

TM2D1 TM2 domain containing 1 1.372504 0.03854133

Amyotrophic lateral sclerosis 2 (juvenile)

ALS2CR8 chromosome region, candidate 8 1.372445 0.006561 caspase 6, apoptosis-related cysteine

CASP6 peptidase 1.372269 0.04203738

MGC16385 Hypothetical protein MGC 16385 1.372209 0.03824835

SFRS17A splicing factor, arginine/serine-rich 17A 1.371645 0.04315668

RXRG retinoid X receptor, gamma 1.371558 0.01357285

ACACB acetyl-CoA carboxylase beta 1.371543 0.01865922

KIAA1310 KIAA1310 1.371445 0.03626434

VEGFA vascular endothelial growth factor A 1.371401 0.00112732

Family with sequence similarity 74, member

FAM74A3 A3 1.371 195 0.04290608

Neural precursor cell expressed,

NEDD1 developmentally down-regulated 1 1.371 19 0.0359751

OR2T3 Olfactory receptor, family 2, subfamily T, 1.371188 0.0318152

DB I/ 69437516. I Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value member 3

solute carrier family 16, member 10 (aromatic

SLC16A10 amino acid transporter) 1.371154 0.02266337 vacuolar protein sorting 24 homolog (S.

VPS24 cerevisiae) 1.371119 0.04148419

CD44 CD44 molecule (Indian blood group) 1.370793 0.00355826

TAT tyrosine aminotransferase 1.370675 0.01325271

CLCNKA chloride channel Ka 1.370649 0.00486945

NOTCH2 Notch homolog 2 (Drosophila) 1.370623 0.0341 1534 solute carrier family 5 (sodium/glucose

SLC5A10 cotransporter), member 10 1.37042 0.04271008 purinergic receptor P2Y, G-protein coupled,

P2 Y13 13 1.370289 0.00291615

NCAPH non-SMC condensin I complex, subunit H 1.370164 0.01932908

PRSS22 protease, serine, 22 1.370127 0.04061674

TMEM87B transmembrane protein 87B 1.369897 0.0223541

PTPRH protein tyrosine phosphatase, receptor type, H 1.369696 0.03119341 janus kinase and microtubule interacting

JAKMIP1 protein 1 1.369683 0.01769588 intrafiagellar transport 74 homolog

IFT74 (Chlamydomonas) 1.369324 0.01094548

TBC1D4 TBC1 domain family, member 4 1.369181 5.58E-05

NUP210L nucleoporin 210kDa-like 1.369063 0.02464659

Olfactory receptor, family 6, subfamily W,

OR6W1P member 1 pseudogene 1.369057 0.04445932

SNAP29 synaptosomal-associated protein, 29kDa 1.368977 0.04802207

Golgi autoantigen, golgin subfamily a, 2-like,

GOLGA2LY1 Y-linked 1 1.368455 0.00642459

CDC 14 cell division cycle 14 homolog B (S.

CDC14B cerevisiae) 1.368453 0.04864209

TRIM45 tripartite motif-containing 45 1.36841 0.02057028

Cl lorf2 chromosome 11 open reading frame 2 1.368238 0.04591136

MERTK c-mer proto-oncogene tyrosine kinase 1.368201 0.01656551

Basic, immunoglobulin-like variable motif

BIVM containing 1.36808 0.02640504

NADPH oxidase, EF-hand calcium binding

NOX5 domain 5 1.367954 0.04018162

MEF2B myocyte enhancer factor 2B 1.367631 0.03665346

ANGPTL4 Angiopoietin-like 4 1.36763 0.03038604

RGS22 regulator of G-protein signaling 22 1.367621 0.01221356

CTN BL1 catenin, beta like 1 1.367091 0.01718999 neutral sphingomyelinase (N-SMase)

NSMAF activation associated factor 1.367032 0.03987999

HAMP hepcidin antimicrobial peptide 1.366953 0.01646212

PRDX6 peroxiredoxin 6 1.366944 0.04515275

ATP-binding cassette, sub-family A (ABC1),

ABCA1 member 1 1.366742 0.00856212

TTL tubulin tyrosine ligase 1.366725 0.02531198

C4orf41 chromosome 4 open reading frame 41 1.366403 0.01849862

C17orf63 chromosome 17 open reading frame 63 1.366389 0.03570733

DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

SOX13 SPvY (sex determining region Y)-box 13 1.36636 0.01564496 pre-B-cell leukemia homeobox interacting

PBXIP1 protein 1 1.366227 0.00453036

TCTN1 tectonic family member 1 1.366123 0.010648

PRKD1 protein kinase Dl 1.366096 0.02015636

NFE2L1 nuclear factor (erythroid-derived 2)-like 1 1.366058 0.00030326

GRB2 -binding adaptor protein,

GAPT transmembrane 1.366056 0.00139747

TNF tumor necrosis factor 1.365785 0.01449054

IK IK cytokine, down-regulator of HLA II 1.365648 0.01056745

PTPRD protein tyrosine phosphatase, receptor type, D 1.365298 0.02363435

ZZZ3 zinc finger, ZZ-type containing 3 1.36524 0.02901362

ODF1 outer dense fiber of sperm tails 1 1.365172 0.02776627

NTRK2 neurotrophic tyrosine kinase, receptor, type 2 1.365093 0.02245205

KIAA0195 KIAA0195 1.365032 0.02929526

DUSP5P dual specificity phosphatase 5 pseudogene 1.364973 0.04615392

POLR1D polymerase (RNA) I polypeptide D, 16kDa 1.364918 0.02725572

ENPEP glutamyl aminopeptidase (aminopeptidase A) 1.364897 0.0451536 adenylate cyclase activating polypeptide 1

ADCYAPIRI (pituitary) receptor type I 1.364667 0.0398011

FAM65B family with sequence similarity 65, member B 1.364604 0.02320728

CENPK centromere protein K 1.364588 0.03575031

MTERFD2 MTERF domain containing 2 1.36445 0.01687718

ATP8B2 ATPase, class I, type 8B, member 2 1.364282 0.01260885 pleckstrin homology domain containing,

PLEKHH2 family H (with MyTH4 domain) member 2 1.364214 0.02614524

NFU1 iron-sulfur cluster scaffold homolog

NFU1 (S. cerevisiae) 1.364152 0.02126921

Rho/Rac guanine nucleotide exchange factor

ARHGEF2 (GEF) 2 1.364141 0.0009248

METTL3 methyltransferase like 3 1.364042 0.00405217

NGFI-A binding protein 2 (EGR1 binding

NAB2 protein 2) 1.364006 0.02567161 bile acid CoA: amino acid N-acyltransferase

BAAT (glycine N-choloyltransferase) 1.363683 0.02579747

WDR44 WD repeat domain 44 1.363614 0.02783348

UDP-GlcNAc:betaGal beta-l,3-N-

B3GNTL1 acetylglucosaminyltransferase-like 1 1.363544 0.00190917

EMILIN3 elastin microfibril interfacer 3 1.363472 0.00980223

C15orf40 chromosome 15 open reading frame 40 1.363453 0.04965862 methylenetetrahydrofolate dehydrogenase

MTHFD1L (NADP+ dependent) 1-like 1.363389 0.00547608

TDRD5 tudor domain containing 5 1.363085 0.02402684

PCDHB5 protocadherin beta 5 1.363007 0.01410305 cytochrome P450, family 2, subfamily A,

CYP2A7 polypeptide 7 1.36287 0.03869986 polymerase (RNA) II (DNA directed)

POLR2C polypeptide C, 33kDa 1.362858 0.04997226 adenosine deaminase, RNA-specific, B2

ADARB2 (RED2 homolog rat) 1.362617 0.02314728

)B 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P

Change value

solute carrier family 11 (proton-coupled

SLC11A2 divalent metal ion transporters), member 2 1.362551 0.00212935 regulator of chromosome condensation

(RCC1) and BTB (POZ) domain containing

RCBTB2 protein 2 1.362522 0.0387415

SUSD4 sushi domain containing 4 1.362469 0.04400647

NPC1 Niemann-Pick disease, type CI 1.362315 0.04477366

ADAMDEC1 ADAM-like, decysin 1 1.362129 0.03679769

GMPPA GDP-mannose pyrophosphorylase A 1.362062 0.03362215

MYO10 myosin X 1.361879 0.04208556

DOCK1 dedicator of cytokinesis 1 1.361725 0.006188

ASB16 ankyrin repeat and SOCS box-containing 16 1.361515 0.02673649 leucine rich repeat and fibronectin type III

LRFN5 domain containing 5 1.361441 0.00683786

SCOC short coiled-coil protein 1.361401 0.02982515

FLJ43950 FAM75-like protein FLJ46321 pseudogene 1.36124 0.03910104

PRKCZ protein kinase C, zeta 1.360589 0.0125831

BRPF1 bromodomain and PHD finger containing, 1 1.360487 0.03928809

PTPRJ protein tyrosine phosphatase, receptor type, J 1.360438 0.03523859 tumor necrosis factor (ligand) superfamily,

TNFSF1 1 member 11 1.360371 0.01940588

FZD3 frizzled homolog 3 (Drosophila) 1.36018 0.03737165

PITX3 paired-like homeodomain 3 1.360032 0.03254832

ZCCHC2 zinc finger, CCHC domain containing 2 1.359997 0.03782226

Pantothenate kinase 2 (Hallervorden-Spatz

PANK2 syndrome) 1.359972 0.01813668

UDP-N-acteylglucosamine

UAP1 pyrophosphorylase 1 1.359785 0.01606561

C8orf37 chromosome 8 open reading frame 37 1.359433 0.01568876

ESR2 estrogen receptor 2 (ER beta) 1.359245 0.02848424

DEAH (Asp-Glu-Ala-His) box polypeptide

DHX38 38 1.359196 0.04968719

ZXDC ZXD family zinc finger C 1.359056 0.04434111

TATA box binding protein (TBP)-associated

TAF1B factor, RNA polymerase I, B, 63kDa 1.35891 0.00465628

COL11A1 collagen, type XI, alpha 1 1.358775 0.01500244 leucine-rich repeat-containing G protein-

LGR4 coupled receptor 4 1.358736 0.02256386

VIL1 villin 1 1.358667 0.03021292

GLIS2 GLIS family zinc finger 2 1.358655 0.02208258

IL1R2 Interleukin 1 receptor, type II 1.358531 0.04399534

CKB creatine kinase, brain 1.358461 0.01419595

Rtfl, Pafl/RNA polymerase II complex

RTF1 component, homolog (S. cerevisiae) 1.358008 0.00507983 solute carrier family 34 (sodium phosphate),

SLC34A1 member 1 1.357953 0.01540008

RLF rearranged L-myc fusion 1.357779 0.00608573 dual-specificity tyrosine-(Y)-phosphorylation

DYRK4 regulated kinase 4 1.357452 0.01059005

SLC30A8 solute carrier family 30 (zinc transporter), 1.357366 0.04578163

DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value member 8

poliovirus receptor-related 1 (herpesvirus

PVRL1 entry mediator C) 0.01512735 HFE hemochromatosis 0.03804853

3'-phosphoadenosine 5'-phosphosulfate

PAPSS2 synthase 2 0.01527324

USP5 ubiquitin specific peptidase 5 (isopeptidase T) 0.02266555

PDLIM5 PDZ and LIM domain 5 0.03327639

DEAD (Asp-Glu-Ala-Asp) box polypeptide

DDX25 25 0.00745677 CDH18 cadherin 18, type 2 0.01178932

ER degradation enhancer, mannosidase alpha¬

EDEM3 like 3 1.356732 0.04196012

CD59 molecule, complement regulatory

CD59 protein 0.00238596 LLGL1 lethal giant larvae homolog 1 (Drosophila) 0.03396635 HARS histidyl-tRNA synthetase 0.03079558 GPR111 G protein-coupled receptor 111 0.01129072 solute carrier family 28 (sodium-coupled

SLC28A3 nucleoside transporter), member 3 0.01558433

SC65 synaptonemal complex protein SC65 0.0041156

ZNF544 zinc fmger protein 544 0.03669101

TNNT3 troponin T type 3 (skeletal, fast) 0.01223845

ZNF236 zinc finger protein 236 0.00612352

KIAA0664 KIAA0664 0.00939652 integrin-linked kinase-associated

ILKAP serine/threonine phosphatase 2C 1.35462 0.00485523 fibroblast growth factor 3 (murine mammary

tumor virus integration site (v-int-2) oncogene

FGF3 homolog) 0.04298606 PELI1 pellino homolog 1 (Drosophila) 0.01691951 ZNHIT2 zinc finger, HIT type 2 0.04183563 SIRPB1 signal-regulatory protein beta 1 0.01437671 leucine-rich repeats and calponin homology

LRCH1 (CH) domain containing 1 0.00280028 aryl-hydrocarbon receptor nuclear

ARNT2 translocator 2 0.00923458

ATP-binding cassette, sub-family C

ABCC2 (CFTR/MRP), member 2 0.01324965

ADAM23 ADAM metallopeptidase domain 23 0.00519005

NLRC5 NLR family, CARD domain containing 5 0.0138878

UDP-N-acetyl-alpha-D- galactosamine:polypeptide N-

GALNTL2 acetylgalactosaminyltransferase-like 2 0.03969585 CIDEC cell death-inducing DFFA-like effector c 0.01386864 solute carrier family 9 (sodium/hydrogen

SLC9A7 exchanger), member 7 1.352213 0.03119589 family with sequence similarity 87, member

FAM87A A 0.02843837 MME membrane metallo-endopeptidase 0.04281673 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

PPIL2 peptidylprolyl isomerase (cyclophiiin)-like 2 0.03170762 FBXL4 F-box and leucine-rich repeat protein 4 0.00412396 carcinoembryonic antigen-related cell

CEACAM20 adhesion molecule 20 1.35193 0.01783611 serum response factor (c-fos serum response

S F element-binding transcription factor) 0.02938074 PIP prolactin-induced protein 0.02836164

ANKRD30A ankyrin repeat domain 3 OA 0.03178457

SNCAIP synuclein, alpha interacting protein 0.00842294

GTPBP1 GTP binding protein 1 0.01449782 growth factor independent IB transcription

GFI1B repressor 0.04386037

ATM ataxia telangiectasia mutated 0.02307203

LYST lysosomal trafficking regulator 0.00716237

OXTR oxytocin receptor 0.02047591

ATP synthase, H+ transporting, mitochondrial

ATP5L2 F0 complex, subunit G2 0.02899822 DEN D3 DENN/MADD domain containing 3 0.00428396 nucleolar complex associated 2 homolog (S.

NOC2L cerevisiae) 1.350431 0.04666038 synaptonemal complex central element

SYCE1 protein 1 0.04034105 KIAA0415 IAA0415 0.04599724 CXXC1 CXXC finger 1 (PHD domain) 0.03108404 NUAK1 NUAK family, SNFl -like kinase, 1 0.04767112 v-maf musculoaponeurotic fibrosarcoma

MAF oncogene homolog (avian) 1.349925 0.03533849

ADAM metallopeptidase with

ADAMTS10 thrombospondin type 1 motif, 10 0.00906533

KLF5 Kruppel-like factor 5 (intestinal) 0.03913202

PAPD4 PAP associated domain containing 4 0.01316031

RGS17 regulator of G-protein signaling 17 0.03025957

KCNIP2 Kv channel interacting protein 2 0.02853969

RASAL2 RAS protein activator like 2 0.04056111

CNRIP1 cannabinoid receptor interacting protein 1 0.0092194

TARBP2 TAR (HIV-1) RNA binding protein 2 0.0213518

AVL9 AVL9 homolog (S. cerevisiase) 0.03542439 sema domain, immunoglobulin domain (Ig),

SEMA3B short basic domain, secreted, (semaphorin) 3B 0.0227655

ZNF451 zinc finger protein 451 0.04749371

MIP major intrinsic protein of lens fiber 0.00400498

DNAI1 dynein, axonemal, intermediate chain 1 0.01203404

SLC38A5 solute carrier family 38, member 5 0.04248543

ZFYVE26 zinc finger, FYVE domain containing 26 0.04363

ODF2L outer dense fiber of sperm tails 2-like 0.01729239

ITPR2 inositol 1,4,5-triphosphate receptor, type 2 0.04400182

ZNF764 zinc finger protein 764 0.00620326

ADCK4 aarF domain containing kinase 4 0.02276393

EFHA1 EF-hand domain family, member Al 0.01216572

DIAPH3 diaphanous homolog 3 (Drosophila) 0.03802677 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

KIF9 kinesin family member 9 1.346678 0.02665295 kelch repeat and BTB (POZ) domain

KBTBD10 containing 10 1.346583 0.04517275 v-akt murine thymoma viral oncogene

AKT2 homolog 2 1.346576 0.040245

ATPase, H+ transporting, lysosomal

ATP6V1B1 56/58kDa, VI subunit Bl 1.345892 0.03333946

F12 coagulation factor XII (Hageman factor) 1.345592 0.0046184

KIF13A kinesin family member 13A 1.345497 0.00072713

TRBV7-2 T cell receptor beta variable 7-2 1.345457 0.00970627

SCLT1 sodium channel and clathrin linker 1 1.345172 0.02022515

ATP synthase, H+ transporting, mitochondrial

ATP5S F0 complex, subunit s (factor B) 1.344751 0.01699017

NT5E 5'-nucleotidase, ecto (CD73) 1.344379 0.01792402 syntrophin, beta 1 (dystrophin-associated

SNTB1 protein Al, 59kDa, basic component 1) 1.344235 0.03577983

C20orfl60 chromosome 20 open reading frame 160 1.34407 0.03316357 hairy/enhancer-of-split related with YRPW

HEY2 motif 2 1.343975 0.03234805

SCMH1 sex comb on midleg homolog 1 (Drosophila) 1.34362 0.04399927

DLL1 delta-like 1 (Drosophila) 1.343162 0.02388195

KRT81 keratin 81 1.342955 0.03566106 alveolar soft part sarcoma chromosome

ASPSCR1 region, candidate 1 1.342913 0.03671779

LYPD4 LY6/PLAUR domain containing 4 1.342848 0.04666735 procollagen-lysine, 2-oxoglutarate 5-

PLOD3 dioxygenase 3 1.342835 0.02428522

CES2 Carboxylesterase 2 (intestine, liver) 1.342819 0.01927775

TFF3 trefoil factor 3 (intestinal) 1.342781 0.03513944 protein disulfide isomerase family A, member

PDIA5 5 1.34214 0.03101883

HSPG2 heparan sulfate proteoglycan 2 1.341774 0.03447131

KLHDC10 kelch domain containing 10 1.34146 0.04514183

RBM7 R A binding motif protein 7 1.341205 0.01218817

DENND1C DENN/MADD domain containing 1C 1.341178 0.03422802

ATG16 autophagy related 16-like 1 (S.

ATG16L1 cerevisiae) 1.34111 0.03484506

TMEM35 transmembrane protein 35 1.340953 0.04831484 myocilin, trabecular meshwork inducible

MYOC glucocorticoid response 1.340916 0.03716645

SMOC2 SPARC related modular calcium binding 2 1.340814 0.03545095

CDCA8 Cell division cycle associated 8 1.340746 0.04499828

ZNF433 zinc finger protein 433 1.340633 0.00429054

LOC339524 hypothetical LOC339524 1.339964 0.04932416

KIAA1383 KIAA1383 1.339459 0.00376021

FLJ43860 FLJ43860 protein 1.339306 0.02548869

TMEM187 transmembrane protein 187 1.338988 0.01389232 protein tyrosine phosphatase-like (proline

PTPLA instead of catalytic arginine), member A 1.338969 0.037401

MTX2 metaxin 2 1.338733 0.0334663

DB1/ 69437₅16.1 Supplemental Tabic 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value family with sequence similarity 73, member

FAM73A A 1.338713 0.00397283

LCP1 lymphocyte cytosolic protein 1 (L-plastin) 1.338614 0.04071473

TET1 tet oncogene 1 1.338454 0.03052802

CCL16 chemokine (C-C motif) ligand 16 1.338375 0.02109751

POU2AF1 POU class 2 associating factor 1 1.338032 0.02411808

ZNF575 zinc finger protein 575 1.338017 0.0417702

DNAH11 dynein, axonemal, heavy chain 11 1.337979 0.01880007 von Willebrand factor A domain containing

VWA5B1 5B1 1.337776 0.00609771

MAD1L1 MAD 1 mitotic arrest deficient-like 1 (yeast) 1.337675 0.0490912 family with sequence similarity 71 , member

FAM71F1 Fl 1.33763 0.00878194

TRAPPC9 N/A 1.337554 0.01651589

Clorf201 chromosome 1 open reading frame 201 1.337552 0.0498056

OR52E5 N/A 1.3375 0.03682626 polymerase (R A) III (DNA directed)

POLR3C polypeptide C (62kD) 1.337476 0.01864437

PRMT3 protein arginine methyltransferase 3 1.337342 0.03303852

KIF17 kinesin family member 17 1.336691 0.01760912

LIPC lipase, hepatic 1.336691 0.0039318

ARMC4 armadillo repeat containing 4 1.336666 0.04505778

CCDC60 coiled-coil domain containing 60 1.336495 0.00361605

EGLN1 egl nine homolog 1 (C. elegans) 1.336453 0.03867409

CATSPER1 cation channel, sperm associated 1 1.336405 0.0332202

SETDB2 SET domain, bifurcated 2 1.336084 0.02125444 nucleolar complex associated 4 homolog (S.

NOC4L cerevisiae) 1.335968 0.0161945

CDYL chromodomain protein, Y-like 1.335878 0.02791548 calcium/calmodulin-dependent protein kinase

CAMK2B II beta 1.335812 0.04798184 methylenetetrahydrofolate dehydrogenase

MTHFD2L (NADP+ dependent) 2-like 1.335717 0.04103293

IGHG2 N/A 1.335709 0.04491141

FBX024 F-box protein 24 1.335484 0.01106863

PCBP1 poly(rC) binding protein 1 1.33547 0.01595027

MPDZ multiple PDZ domain protein 1.335134 0.04286986 protein phosphatase 2, regulatory subunit B',

PPP2R5B beta 1.335088 0.02170275 family with sequence similarity 172, member

FAM172A A 1.335005 0.02084294

COG2 component of oligomeric golgi complex 2 1.334892 0.04709598

ICMT isoprenylcysteine carboxyl methyltransferase 1.334878 0.03860215

KIAA0430 KIAA0430 1.334773 0.01020301 cyclin-dependent kinase inhibitor 2C (pi 8,

CDKN2C inhibits CDK4) 1.33462 0.04260088

STIL SCL/TAL1 interrupting locus 1.334613 0.03388643

PRSS7 Protease, serine, 7 (enterokinase) 1.334333 0.01142169

XRCC6BP 1 XRCC6 binding protein 1 1.334324 0.02789105

EPS8L3 EPS8-like 3 1.334213 0.04695945

DB1/ ₆943751₆.1 Supplemental Table 1. Gene Transcripts Up regulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

DNAL1 dynein, axonemal, light chain 1 0.00728948

MVP major vault protein 0.01031094

C14orfl53 chromosome 14 open reading frame 153 0.01271846

GPNMB glycoprotein (transmembrane) nmb 0.03873986

MRPL14 mitochondrial ribosomal protein L14 0.04564392

PRIM2 primase, DNA, polypeptide 2 (58kDa) 0.04472306

C12orf53 chromosome 12 open reading frame 53 0.04842264

ARRB1 arrestin, beta 1 0.04064721

MYOIE myosin IE 0.02617532 acyl-CoA synthetase long-chain family

ACSLl member 1 1.332807 0.04712455 family with sequence similarity 48, member

FAM48A A 0.03909798 NLR 12 NLR family, pyrin domain containing 12 0.02016962 YTHDF1 YTH domain family, member 1 6.74E-05 TE TEK tyrosine kinase, endothelial 0.02096853 heterogeneous nuclear ribonucleoprotein U-

H RNPUL1 like 1 0.03824297 C17orf68 chromosome 17 open reading frame 68 0.01659617 COL4A6 collagen, type IV, alpha 6 0.02055205 ADAM 15 ADAM metallopeptidase domain 15 0.04166114 ZNF230 zinc finger protein 230 0.03172799 leucine-rich repeats and immunoglobulin-like

LRIG1 domains 1 1.332089 0.02564779 major histocompatibility complex, class II,

HLA-DOB DO beta 0.02622731 GST02 glutathione S-transferase omega 2 0.04470831

SIN3 homolog A, transcription regulator

SIN3A (yeast) 0.02326265 CNT 1 contactin 1 0.0209712 TMPRSS3 transmembrane protease, serine 3 0.00957193 MAGEA4 melanoma antigen family A, 4 0.0305814

Cytidine monophosphate N-acetylneuraminic

CMAS acid synthetase 1.330734 0.01823308 family with sequence similarity 156, member

F AM 156 A A 0.03781504

SPG11 Spastic paraplegia 11 (autosomal recessive) 0.02444527

SLC26A10 solute carrier family 26, member 10 0.01287172

ASB7 ankyrin repeat and SOCS box -containing 7 0.04772905

MPRIP myosin phosphatase Rho interacting protein 0.04741189

ZNF221 zinc finger protein 221 0.02107807 spen homolog, transcriptional regulator

SPEN (Drosophila) 0.00217947 PMV phosphomevalonate kinase 0.04833547

Nephrosis 2, idiopathic, steroid-resistant

NPHS2 (podocin) 0.02886971

SNAP23 synaptosomal-associated protein, 23kDa 0.03566571

MIPEP mitochondrial intermediate peptidase 0.02939542

UNC5CL unc-5 homolog C (C. elegans)-like 0.03819333

I PPL1 inositol polyphosphate phosphatase-like 1 0.00979076 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

NCF2 neutrophil cytosolic factor 2 1.32983 0.03949076

DTX3L deltex 3 -like (Drosophila) 1.329799 0.00180118 hCG 2020170 HCG2020170 1.329766 0.01539661

WDR25 WD repeat domain 25 1.329556 0.02098528

U C84A Unc-84 homolog A (C. elegans) 1.329388 0.00510734

PXMP4 peroxisomal membrane protein 4, 24kDa 1.329312 0.04663567

RHBG Rh family, B glycoprotein (gene/pseudogene) 1.329034 0.03111524

ZHX1 zinc fingers and omeoboxes 1 1.328792 0.02722766

Smith-Magenis syndrome chromosome

SMC 7L region, candidate 7-like 1.328557 0.00411243 protein associated with topoisomerase II

PATL1 homolog 1 (yeast) 1.328315 0.03968027

SLC9A11 solute carrier family 9, member 1 1 1.328309 0.0193753 family with sequence similarity 105, member

F AM 105 A A 1.32814 0.00467247

PSRC1 proline/serine-rich coiled-coil 1 1.328033 0.04722541 dapper, antagonist of beta-catenin, homolog 3

DACT3 (Xenopus laevis) 1.327948 0.02331086 family with sequence similarity 38, member

FAM38A A 1.327903 0.00802084

CDC2L1 N/A 1.327887 0.0153454

CCM2 Cerebral cavernous malformation 2 1.327782 0.02434867

Glycerophosphodiester pho sphodiesterase

GDPD1 domain containing 1 1.32778 0.00292559

TRIM41 tripartite motif-containing 41 1.327768 0.01154423

COL15A1 collagen, type XV, alpha 1 1.327586 0.020284

TMEM161B transmembrane protein 161B 1.32758 0.04183431

ACAD 11 acyl-CoA dehydrogenase family, member 11 1.327511 0.01857637

DPPA4 Developmental pluripotency associated 4 1.32749 0.00698447

PRR13 proline rich 13 1.327383 0.02554162 microtubule-associated protein, RP/EB

MAPRE3 family, member 3 1.327354 0.03360774

NSUN4 NOP2/Sun domain family, member 4 1.327342 0.03660922

ZNF500 zinc finger protein 500 1.327317 0.00726811 membrane-spanning 4-domains, subfamily A,

MS4A14 member 14 1.327271 0.02715879

MBD6 methyl-CpG binding domain protein 6 1.326963 0.01599676

MCTP2 multiple C2 domains, transmembrane 2 1.326518 0.04849203

ATP-binding cassette, sub-family C

ABCC9 (CFTR MRP), member 9 1.326231 0.03610157

EHF ets homologous factor 1.326027 0.04824006

GIF gastric intrinsic factor (vitamin B synthesis) 1.325988 0.01793027

SLC24A5 Solute carrier family 24, member 5 1.325788 0.02700464

ZNF282 zinc finger protein 282 1.325592 0.04251978

ICAIL islet cell autoantigen l,69kDa-like 1.325277 0.01671185

PLG plasminogen 1.325181 0.02059755

ZNF461 zinc finger protein 461 1.325137 0.03479437

C14orfl 78 chromosome 14 open reading frame 178 1.325086 0.03532542

AN RD53 ankyrin repeat domain 53 1.325033 0.0308792

ZNF318 zinc finger protein 318 1.324888 0.04057492

DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Ceils Gene Symbol Gene Description Fold Ttest P

Change value

KIF20B kinesin family member 20B 0.00916296 CT45A2 cancer/testis antigen family 45, member A2 0.01496868 TRIML2 tripartite motif family-like 2 0.02904986 FBX05 F-box protein 5 0.0080861 1 serpin peptidase inhibitor, clade H (heat shock

protein 47), member 1 , (collagen binding

SERPI H1 protein 1) 0.01919945

HAUS5 HAUS augmin-like complex, subunit 5 0.00324377

PKD1L2 polycystic kidney disease 1 -like 2 0.03252629

Chromodomain helicase DNA binding protein

CHD5 5 0.03775408

ADAM metallopeptidase domain 19 (meltrin

ADAM 19 beta) 0.01218115

CCR4-NOT transcription complex, subunit 6-

CNOT6L like 0.01210832

KCNT2 Potassium channel, subfamily T, member 2 0.04130177

HORMAD2 HORMA domain containing 2 0.04105609

PEX6 peroxisomal biogenesis factor 6 0.00710564

CCDC79 coiled-coil domain containing 79 0.03779917

BTN3A2 butyrophilin, subfamily 3, member A2 0.04746066

C9orf9 chromosome 9 open reading frame 9 0.00782996 adaptor-related protein complex 4, epsilon 1

AP4E1 subunit 0.00619788

ATN1 atrophin 1 0.02343773

C18orf22 chromosome 18 open reading frame 22 0.04587944

LEPR leptin receptor 0.04430447

MED1 mediator complex subunit 1 0.04246086

C10orf4 Chromosome 10 open reading frame 4 0.01735236 benzodiazapine receptor (peripheral)

BZRAP1 associated protein 1 0.03558951 HS6ST1 heparan sulfate 6-O-sulfotransferase 1 0.01662026 latent transforming growth factor beta binding

LTBP4 protein 4 0.0357762 MANBA mannosidase, beta A, lysosomal 0.0144055

TBC1 domain family, member 8B (with

TBC1D8B GRAM domain) 1.321661 0.02024654 acyl-CoA synthetase bubblegum family

ACSBG2 member 2 0.02038367 PMS2L5 postmeiotic segregation increased 2-like 5 0.04674914

Asthma-associated alternatively spliced gene

AAA1 1 0.0125656 TOP3B topoisomerase (DNA) III beta 0.0448924 ZBTB44 zinc finger and BTB domain containing 44 0.00360563 SMO smoothened homolog (Drosophila) 0.03439192 ectonucleoside triphosphate

ENTPD3 diphosphohydrolase 3 0.01633764

MSLN mesothelin 0.03681721

WDR72 WD repeat domain 72 0.02144796

TMEM144 transmembrane protein 144 0.01405535

MED7 mediator complex subunit 7 0.04881557

DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value aryl hydrocarbon receptor nuclear

ARNTL translocator-like 1.320026 0.01245522 protein tyrosine phosphatase, non-receptor

PTPN23 type 23 1.320026 0.00645288

FSTL4 follistatin-like 4 1.319819 0.02501339

TMEM219 transmembrane protein 219 1.319745 0.02673344 phosphoribosylglycinamide

formyltransferase,

phosphoribosylglycinamide synthetase,

GART phosphoribosylaminoimidazole synthetase 1.31974 0.04033209

PHKA2 phosphorylase kinase, alpha 2 (liver) 1.31943 0.04301133

DMGDH dimethylglycine dehydrogenase 1.319296 0.03413839

C14orfl47 chromosome 14 open reading frame 147 1.319192 0.03875552

TRIM22 tripartite motif-containing 22 1.319187 0.04164827 glutamic pyruvate transaminase (alanine

GPT2 aminotransferase) 2 1.31914 0.00699189

SSH1 slingshot homolog 1 (Drosophila) 1.318798 0.0307019

EMB embigin homolog (mouse) 1.318438 0.03974458

MSTOl misato homolog 1 (Drosophila) 1.318428 0.01888897

PRKCQ protein kinase C, theta 1.318396 0.03206098

ADAM metallopeptidase with

ADAMTS13 thrombospondin type 1 motif, 13 1.318309 0.02353973

PDRG1 p53 and DNA-damage regulated 1 1.318285 0.04255131

SNRK SNF related kinase 1.318247 0.02386553

C9orfl00 chromosome 9 open reading frame 100 1.318221 0.01355025

TRIM56 tripartite motif-containing 56 1.318199 0.03539142

GCNT1 glucosaminyl (N-acetyl) transferase 1, core 2 1.318145 0.0106976

ARHGEF5L N/A 1.318054 0.03589274

CPNE7 copine VII 1.318018 0.04033407

UBE2S ubiquitin-conjugating enzyme E2S 1.317991 0.03399721

ZNF321 Zinc finger protein 321 1.317951 0.03230609

ZNF143 zinc finger protein 143 1.317349 0.04315744

RNF144B ring finger protein 144B 1.317336 0.00626051

USP24 ubiquitin specific peptidase 24 1.317279 0.04933808

Clorfl22 chromosome 1 open reading frame 122 1.317239 0.02093694

ZFP28 zinc finger protein 28 homolog (mouse) 1.3171 18 0.00740862

GUCY1B3 guanylate cyclase 1 , soluble, beta 3 1.317051 0.00086926

PRDM16 PR domain containing 16 1.317007 0.04796125

KCP kielin chordin-like protein 1.316988 0.0088902

PCSK5 proprotein convertase subtilisin/kexin type 5 1.316956 0.01056173

BCL2/adenovirus E1B 19kD interacting

BNIPL protein like 1.316952 0.03989385 solute carrier family 22 (organic anion/urate

SLC22A12 transporter), member 12 1.31688 0.04811674 RAI2 retinoic acid induced 2 1.316758 0.03820596

OLFML2B olfactomedin-like 2B 1.31662 0.01997839

C8orf45 chromosome 8 open reading frame 45 1.316541 0.04426162

KLKB1 kallikrein B, plasma (Fletcher factor) 1 1.316373 0.0385414

TEX14 testis expressed 14 1.316226 0.03827991

PON3 paraoxonase 3 1.315951 0.03474527 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

DOCK4 dedicator of cytokinesis 4 1.315887 0.02646044 nuclear factor of kappa light polypeptide gene

NFKBIL2 enhancer in B-cells inhibitor-like 2 1.315349 0.01640883

CCNB1 cyclin Bl 1.315053 0.02415274

RNF213 ring finger protein 213 1.31469 0.00272093

CDH9 cadherin 9, type 2 (Tl-cadherin) 1.314628 0.0156202 solute carrier family 15 (H+/peptide

SLC15A2 transporter), member 2 1.314537 0.01002407

GPATCH8 G patch domain containing 8 1.314467 0.03038614

IRX1 iroquois homeobox 1 1.313925 0.01156482

LPHN2 latrophilin 2 1.313747 0.00687677

TMEM146 transmembrane protein 146 1.313705 0.02082781

CDK3 cyclin-dependent kinase 3 1.313305 0.01672594 low density lipoprotein receptor-related

LRP2 protein 2 1.313296 0.00968269

TG thyroglobulin 1.313285 0.00185045

GPR171 G protein-coupled receptor 171 1.313243 0.04135709

C14orfl45 chromosome 14 open reading frame 145 1.312749 0.03212212 growth factor independent 1 transcription

GFI1 repressor 1.312642 0.01046655

EIF4H eukaryotic translation initiation factor 4H 1.312594 0.00452783

ACPP acid phosphatase, prostate 1.312577 0.03492758 nudix (nucleoside diphosphate linked moiety

NUDT15 X)-type motif 15 1.312551 0.04340014

ArfGAP with SH3 domain, ankyrin repeat

ASAP3 and PH domain 3 1.312499 0.03870607

PIAS3 protein inhibitor of activated STAT, 3 1.312445 0.02652922

PAN3 poly(A) specific ribonuclease subunit

PAN3 homolog (S. cerevisiae) 1.312377 0.01230948 radial spoke head 10 homolog B

RSPH10B (Chlamydomonas) 1.311911 0.01401368

UROC1 urocanase domain containing 1 1.311867 0.04595685

C6orfl82 Chromosome 6 open reading frame 182 1.311566 0.02633846

S100A7 S 100 calcium binding protein A7 1.311542 0.0142408 myosin, heavy chain 8, skeletal muscle,

MYH8 perinatal 1.31154 0.0245483

LMX1B LIM homeobox transcription factor 1 , beta 1.311513 0.02368958

AHCYL2 adenosylhomocysteinase-like 2 1.311322 0.04070981

CCDC135 coiled-coil domain containing 135 1.311143 0.02857

WHSC2 Wolf-Hirschhorn syndrome candidate 2 1.311082 0.03526217

COL8A2 collagen, type VIII, alpha 2 1.310946 0.02539666

Usher syndrome 2A (autosomal recessive,

USH2A mild) 1.310913 0.04391246

ORAOV1 Oral cancer overexpressed 1 1.310757 0.01014515

NUP35 nucleoporin 35kDa 1.310688 0.03504381 calcium channel, voltage-dependent, T type,

CACNA1I alpha 11 subunit 1.310393 0.02761535

SCARA3 scavenger receptor class A, member 3 1.310298 0.04660373 queuine tRNA-ribosyltransferase domain

QTRTD1 containing 1 1.310073 0.03897065

⁾B 1 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

ADAL adenosine deaminase-like 1.309891 0.0379593

PRMT7 protein arginine methyltransferase 7 1.309419 0.01323269 prematurely terminated mRNA decay factor¬

LOC91431 like 1.309402 0.04138642

INADL InaD-like (Drosophila) 1.309387 0.00981621

SYS1 Golgi-localized integral membrane

SYS1 protein homolog (S. cerevisiae) 1.30937 0.0448041 kelch repeat and BTB (POZ) domain

KBTBD11 containing 11 1.309312 0.01421923

TMEM107 transmembrane protein 107 1.309287 0.01165641

ATPase, H+/K+ exchanging, alpha

ATP4A polypeptide 1.309252 0.03384388

C4orf35 chromosome 4 open reading frame 35 1.309181 0.00329241 family with sequence similarity 55, member

FAM55A A 1.309086 0.02141947

SNIP1 Smad nuclear interacting protein 1 1.30902 0.04305763 potassium voltage-gated channel, KQT-like

KCNQ5 subfamily, member 5 1.308923 0.01452584 solute carrier family 20 (phosphate

SLC20A1 transporter), member 1 1.308554 0.01655305

ZNF479 zinc finger protein 479 1.308537 0.03375878

TCN2 transcobalamin II 1.308533 0.01433225

MUT methylmalonyl CoA mutase 1.308487 0.02319145

IRF1 interferon regulatory factor 1 1.308463 0.04031537 testis-specific transcript, Y-linked 14 (non¬

TTTY14 protein coding) 1.308338 0.02764961

MGC4294 hypothetical protein MGC4294 1.308291 0.00833659

HK3 hexokinase 3 (white cell) 1.307948 0.00984782

CNP 2',3'-cyclic nucleotide 3' phosphodiesterase 1.307669 0.03190761

ARHGAP19 Rho GTPase activating protein 19 1.307466 0.02820484

BOC Boc homolog (mouse) 1.307464 0.04120587

HPSE2 heparanase 2 1.307142 0.02069281

HOXA11 homeobox Al 1 1.3071 17 0.02978879

IGSF8 immunoglobulin superfamily, member 8 1.307107 0.04802534

APAF1 apoptotic peptidase activating factor 1 1.306905 0.03041618

GJA8 gap junction protein, alpha 8, 50kDa 1.306617 0.0301685

ENG endoglin 1.306576 0.03736587

PCNA proliferating cell nuclear antigen 1.306526 0.02897492

ZNF234 zinc finger protein 234 1.30646 0.01321066 latent transforming growth factor beta binding

LTBP3 protein 3 1.306433 0.02949493

PRDM4 PR domain containing 4 1.30643 0.04352244

INSL5 insulin-like 5 1.306233 0.01876093

JMJD8 jumonji domain containing 8 1.306173 0.04275968

DnaJ (Hsp40) homolog, subfamily C, member

DNAJC28 28 1.306141 0.0464148

RNF123 ring finger protein 123 1.305908 0.0316032

TEKT1 tektin 1 1.305715 0.01698729

ETN 1 ethanolamine kinase 1 1.305688 0.01828431

PPP2 2D protein phosphatase 2, regulatory subunit B, 1.305577 0.0421285 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

delta isoform

large subunit GTPase 1 homolog (S.

LSG1 cerevisiae) 1.30556 0.02208307

CD40 molecule, TNF receptor superfamily

CD40 member 5 1.305475 0.029036 sulfotransferase family, cytosolic, 1C,

SULT1C4 member 4 1.305438 0.0172204 TMEM190 transmembrane protein 190 1.305362 0.01501063 polymerase (RNA) III (DNA directed)

POLR3D polypeptide D, 44kDa 1.30532 0.01376665 amylo-alpha-1, 6-glucosidase, 4-alpha-

AGL glucanotransferase 1.305308 0.02445334 pleckstrin homology domain containing,

PLEKHG6 family G (with RhoGef domain) member 6 1.305225 0.00992449 xenotropic and polytropic retrovirus receptor

XPR1 1 1.305053 0.00184251 ankyrin repeat and BTB (POZ) domain

ABTB2 containing 2 1.305043 0.02396353

TGM5 transglutaminase 5 1.304837 0.02979951

CDC25B cell division cycle 25 homolog B (S. pombe) 1.304806 0.03726143

TMOD2 tropomodulin 2 (neuronal) 1.30475 0.01772342

TMEM185B transmembrane protein 185B (pseudogene) 1.30461 0.00257445

PHKA1 phosphorylase kinase, alpha 1 (muscle) 1.304453 0.047388

COL19A1 collagen, type XIX, alpha 1 1.304251 0.01176413

SLC26A6 solute carrier family 26, member 6 1.304206 0.01790112 protein tyrosine phosphatase, receptor type, f

polypeptide (PTPRF), interacting protein

PPFIA2 (liprin), alpha 2 1.304138 0.04810995 PNKD Paroxysmal nonkinesigenic dyskinesia 1.304131 0.02809504

Rap guanine nucleotide exchange factor

RAPGEF4 (GEF) 4 1.303909 0.02695454

NLGN4X neuroligin 4, X-linked 1.303813 0.03148034

CLCA1 chloride channel accessory 1 1.303717 0.03919733 polymerase (RNA) II (DNA directed)

POLR2I polypeptide I, 14.5kDa 1.303374 0.04830243

C14orf48 chromosome 14 open reading frame 48 1.303225 0.00358584

VILL villin-like 1.302715 0.04757931 membrane associated guanylate kinase, WW

MAGI2 and PDZ domain containing 2 1.30264 0.02027315 cytochrome P450, family 2, subfamily B,

CYP2B6 polypeptide 6 1.30263 0.01340493

LATS, large tumor suppressor, homolog 1

LATS1 (Drosophila) 1.3025 0.03933197

DOK5 docking protein 5 1.302469 0.01233959

ACACA acetyl-CoA carboxylase alpha 1.302373 0.02462743

PRKD3 protein kinase D3 1.302343 0.04005699

DAPK3 death-associated protein kinase 3 1.302229 0.03626214

C5orfl3 chromosome 5 open reading frame 13 1.302196 0.04509051

WWOX WW domain containing oxidoreductase 1.302119 0.02600082

FA2H fatty acid 2-hydroxylase 1.302021 0.02502105

DB l/ 69437516.1 Supplemental Table 1. Gene Transcripts Upreguiated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

PKN3 protein kinase N3 1.30192 0.0296009

STEAP3 STEAP family member 3 1.301879 0.0185418

MYPN myopalladin 1.301792 0.04028135

PSD pleckstrin and Sec7 domain containing 1.301792 0.00332964

TOX high mobility group box family member

TOX2 2 1.301788 0.00829846

CDC7 cell division cycle 7 homolog (S. cerevisiae) 1.301589 0.03056512

RWDD1L1 N/A 1.301455 0.00671015

SP9 Sp9 transcription factor homolog (mouse) 1.301235 0.04540898 vacuolar protein sorting 41 homolog (S.

VPS41 cerevisiae) 1.301232 0.03671784 sarcoglycan, delta (35kDa dystrophin-

SGCD associated glycoprotein) 1.301221 0.02934646

TRIM36 tripartite motif-containing 36 1.301203 0.01262691

PRR4 proline rich 4 (lacrimal) 1.301132 0.03615856

DnaJ (Hsp40) homolog, subfamily B, member

DNAJB12 12 1.300681 0.04334606 origin recognition complex, subunit 3 -like

ORC3L (yeast) 1.300652 0.01020332

NIMA (never in mitosis gene a)- related

NEK 10 kinase 10 1.300415 0.01710128 translocase of inner mitochondrial membrane

TIMM50 50 homolog (S. cerevisiae) 1.300325 4.55E-05

PCDHGA8 protocadherin gamma subfamily A, 8 1.300313 0.02404996

TECPR1 tectonin beta-propeller repeat containing 1 1.300191 0.03405406

ZNF789 zinc finger protein 789 1.300153 0.03424549

MKRN1 makorin ring finger protein 1 1.299966 0.01476264

MLF1IP MLF1 interacting protein 1.29929 0.03391614

GPR45 G protein-coupled receptor 45 1.29928 0.04904797 progestin and adipoQ receptor family member

PAQR5 V 1.299268 0.00317122

FHDC1 FH2 domain containing 1 1.299248 0.02931807 eukaryotic translation elongation factor 1

EEF1D delta (guanine nucleotide exchange protein) 1.299174 0.02232024

SPAG16 sperm associated antigen 16 1.299145 0.02531261

ZNF175 zinc finger protein 175 1.299129 0.02599533

MSR1 macrophage scavenger receptor 1 1.298769 0.02013449

THOC3 THO complex 3 1.298749 0.02818972 solute carrier family 12 (sodium/chloride

SLC12A3 transporters), member 3 1.298657 0.04427049

TMEM175 transmembrane protein 175 1.298598 0.00703759 eukaryotic translation initiation factor 2-alpha

EIF2AK3 kinase 3 1.298331 0.04888608

TSSC1 tumor suppressing subtransferable candidate 1 1.298268 0.04784076 dihydrolipoamide branched chain transacylase

DBT E2 1.298264 0.03189072

DnaJ (Hsp40) homolog, subfamily C, member

DNAJC14 14 1.297893 0.04993902

SPAG4L Sperm associated antigen 4-like 1.297362 0.00528533

MCC mutated in colorectal cancers 1.297264 0.02171935

DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

COP9 constitutive photomorphogenic

COPS7A homolog subunit 7A (Arabidopsis) 1.297234 0.01501032

MRT04 mRNA turnover 4 homolog (S. cerevisiae) 1.29723 0.02704754

RHD Rh blood group, D antigen 1.297189 0.02262032

TYR03 TYR03 protein tyrosine kinase 1.297133 0.04325744

ATF6 activating transcription factor 6 1.297079 0.04257111

DUSP15 dual specificity phosphatase 15 1.297006 0.02529751

LOC541473 FK506 binding protein 6, 36kDa pseudogene 1.296923 0.00600023

CEND1 cell cycle exit and neuronal differentiation 1 1.296588 0.04442424 interferon regulatory factor 2 binding protein

IRF2BP1 1 1.296464 0.0403163

TMEM179 transmembrane protein 179 1.296444 0.0217629

SPATA12 spermatogenesis associated 12 1.296108 0.01940578

Olfactory receptor, family 2, subfamily W,

OR2W5 member 5 1.296004 0.04316118

GIGYF1 GRB10 interacting GYF protein 1 1.295491 0.03956304

YEATS4 YEATS domain containing 4 1.295452 0.03794617 solute carrier family 10 (sodium/bile acid

SLC10A7 cotransporter family), member 7 1.295385 0.0235016

C17orf55 chromosome 17 open reading frame 55 1.295284 0.0171084

INVS inversin 1.295193 0.00903241

SLC46A3 solute carrier family 46, member 3 1.295174 0.04864538

EMILIN1 elastin microfibril interfacer 1 1.295009 0.0181214

NAALAD2 N-acetylated alpha-linked acidic dipeptidase 2 1.294984 0.0325433

STAB2 stabilin 2 1.294843 0.02909169

CCDC141 coiled-coil domain containing 141 1.294841 0.03543174

PFDN2 prefoldin subunit 2 1.294826 0.02783804

PGM1 phosphoglucomutase 1 1.294817 0.04011517 wingless-type MTV integration site family,

WNT2B member 2B 1.294816 0.01338583

ArfGAP with coiled-coil, ankyrin repeat and

AC API PH domains 1 1.294712 0.00969179

UFC1 ubiquitin-fold modifier conjugating enzyme 1 1.294642 0.04198936

MCF.2 cell line derived transforming

MCF2 sequence 1.294591 0.04438568

MAGEB3 melanoma antigen family B, 3 1.294585 0.01466257 v-src sarcoma (Schmidt-Ruppin A-2) viral

SRC oncogene homolog (avian) 1.294388 0.02949684

POLH polymerase (DNA directed), eta 1.293916 0.04809113

HAP1 huntingtin-associated protein 1 1.293825 0.01962217 runt-related transcription factor 1 ;

RUNX1T1 translocated to, 1 (cyclin D-related) 1.293798 0.00514469

TP53BP2 tumor protein p53 binding protein, 2 1.293725 0.00778505

ESRP2 epithelial splicing regulatory protein 2 1.293654 0.00638682

CRIP3 Cysteine-rich protein 3 1.293478 0.00371955

A2M alpha-2-macroglobulin 1.293429 0.00961782

CCDC114 coiled-coil domain containing 114 1.293346 0.03959844

DnaJ (Hsp40) homolog, subfamily B, member

DNAJB2 2 1.293323 0.00219792

SLC25A40 solute carrier family 25, member 40 1.293282 0.03909541

DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

SPINT2 serine peptidase inhibitor, Kunitz type, 2 1.293191 0.04918457

HIF3A Hypoxia inducible factor 3, alpha subunit 1.293096 0.04351659

TGFBR1 transforming growth factor, beta receptor 1 1.293066 0.01642541

TRIM49 tripartite motif-containing 49 1.293012 0.01757071

NADH dehydrogenase (ubiquinone) 1 alpha

NDUFA10 subcomplex, 10, 42kDa 1.292946 0.04491656 cystic fibrosis transmembrane conductance

regulator (ATP-binding cassette sub-family C,

CFTR member 7) 1.292942 0.01840615

BAT4 HLA-B associated transcript 4 1.292895 0.02567915 amyloid beta (A4) precursor protein-binding,

APBB1 family B, member 1 (Fe65) 1.292641 0.01662514

RBM25 RNA binding motif protein 25 1.292556 0.04894338

HERPUD2 HERPUD family member 2 1.292034 0.04837984

MAP2K2 mitogen-activated protein kinase kinase 2 1.291915 0.00765513

AKAP8L A kinase (PRKA) anchor protein 8 -like 1.291794 0.04370944

RREBl ras responsive element binding protein 1 1.291689 0.00827326

FAM53C family with sequence similarity 53, member C 1.291657 0.01840381

MSH5 mutS homolog 5 (E. coli) 1.291503 0.00094657

EFR3B EFR3 homolog B (S. cerevisiae) 1.291499 0.03382682

MGC24975 Hypothetical protein MGC24975 1.291206 0.01978755

MAN1B1 mannosidase, alpha, class IB, member 1 1.290923 0.03761272

KRT7 keratin 7 1.290891 0.04257891

RBP3 retinol binding protein 3, interstitial 1.290772 0.00495777

NLRP4 NLR family, pyrin domain containing 4 1.290637 0.03772813

CHDH choline dehydrogenase 1.290568 0.02570163

C14orf83 chromosome 14 open reading frame 83 1.290438 0.03660187

SOX30 SRY (sex determining region Y)-box 30 1.290387 0.02018918

MGC21881 hypothetical locus MGC21881 1.290175 0.03433103

HNMT histamine N-methyltransferase 1.290102 0.00921103

KIF24 inesin family member 24 1.290062 0.03501299

GPR176 G protein-coupled receptor 176 1.289767 0.04432081

SFRS16 splicing factor, arginine/serine-rich 16 1.289527 0.00918842

PDE3B phosphodiesterase 3B, cGMP-inhibited 1.289111 0.02490519

ATP-binding cassette, sub-family C

ABCC10 (CFTR/MRP), member 10 1.28892 0.00730162 olfactory receptor, family 2, subfamily C,

OR2C3 member 3 1.288831 0.04451079 calcium/calmodulin-dependent protein kinase

CAMKK2 kinase 2, beta 1.288582 0.00401144

HBXIP hepatitis B virus x interacting protein 1.288507 0.03684191

FERMT1 fermitin family homolog 1 (Drosophila) 1.288475 0.01992465

PCSK2 proprotein convertase subtilisin/kexin type 2 1.288199 0.01907613 cysteine-rich secretory protein LCCL domain

CRISPLD1 containing 1 1.288049 0.02520263 complement component 1, q subcomponent,

C1QB B chain 1.287998 0.00958669

MGC29506 plasma cell-induced ER protein 1 1.287906 0.03621649 guanine nucleotide binding protein (G

GNG5 protein), gamma 5 1.287847 0.0044331

⁾B1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

MAGED1 melanoma antigen family D, 1 1.287519 0.02569332 CASKIN2 CASK interacting protein 2 1.287506 0.03214233 mitogen-activated protein kinase kinase

MAP3K11 kinase 11 1.287394 0.00590728 C12orf27 chromosome 12 open reading frame 27 1.287284 0.03594103

SMEK homo log 3, suppressor of mekl

SMEK3P (Dictyostelium) pseudogene 1.287218 0.01213296 C8orf41 chromosome 8 open reading frame 41 1.287147 0.02624243

StAR-related lipid transfer (START) domain

STARD3 containing 3 1.287005 0.02329359

RPL14 ribosomal protein LI 4 1.286996 0.04389132

ELMOD3 ELMO/CED-12 domain containing 3 1.286807 0.02853122 IAA0513 KIAA0513 1.286421 0.03234515

DIDOl death inducer-obliterator 1 1.28637 0.02217596

SLC43A3 solute carrier family 43, member 3 1.286291 0.00818887

NPC2 Niemann-Pick disease, type C2 1.286232 0.01035146

SIGLEC8 sialic acid binding Ig-like lectin 8 1.285973 0.0432303 core-binding factor, runt domain, alpha

CBFA2T2 subunit 2; translocated to, 2 1.28571 0.00793092

MYH6 myosin, heavy chain 6, cardiac muscle, alpha 1.285655 5.89E-05

C12orf63 chromosome 12 open reading frame 63 1.285351 0.02001726

SHOX2 short stature homeobox 2 1.285337 0.01608284

IFLTD1 intermediate filament tail domain containing 1 1.285219 0.0251623

CT45A5 cancer/testis antigen family 45, member A5 1.285076 0.02092369

CDC42 effector protein (Rho GTPase

CDC42EP4 binding) 4 1.284956 0.01468179 required for meiotic nuclear division 5

RMND5A homolog A (S. cerevisiae) 1.284948 0.01304799 FBXW2 F-box and WD repeat domain containing 2 1.284946 0.03658627 VHL von Hippel-Lindau tumor suppressor 1.284754 0.00453337 MYOM2 myomesin (M-protein) 2, 165kDa 1.284592 0.03781633

CDK5 regulatory subunit associated protein

CDKAL1 1-like 1 1.28459 0.00136589 integrin, alpha X (complement component 3

ITGAX receptor 4 subunit) 1.284505 0.01564835 sema domain, immunoglobulin domain (Ig),

SEMA3E short basic domain, secreted, (semaphorin) 3E 1.284324 0.00568937 chondroitin sulfate proteoglycan 5

CSPG5 (neuroglycan C) 1.284094 0.0016048

DPP9 dipeptidyl-peptidase 9 1.284052 0.04672429

EXOC3 exocyst complex component 3 1.284045 0.04170658 phosphatidylinositol glycan anchor

PIGN biosynthesis, class N 1.283912 0.01937258 selectin P (granule membrane protein

SELP 140kDa, antigen CD62) 1.283742 0.0326095 CGB1 chorionic gonadotropin, beta polypeptide 1 1.283709 0.04475474 PCDHA1 protocadherin alpha 1 1.283621 0.0032591 STK11IP serine/threonine kinase 11 interacting protein 1.283586 0.04232222 phosphoinositide kinase, FYVE finger

PIKFYVE containing 1.283542 0.02186269

DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

AGFG2 ArfGAP with FG repeats 2 1.283524 0.04847402 cleavage stimulation factor, 3' pre-RNA,

CSTF2 subunit 2, 64kDa 1.283423 0.02479593

MTCP1 mature T-cell proliferation 1 1.283365 0.02616361

HDGF hepatoma-derived growth factor 1.283264 0.03225054

SLC38A9 solute carrier family 38, member 9 1.283074 0.01870351

UROD uroporphyrinogen decarboxylase 1.283017 0.00763977

CRX cone-rod homeobox 1.282794 0.04267342

C5orf42 chromosome 5 open reading frame 42 1.282748 0.01191994

TPMT thiopurine S-methyltransferase 1.282727 0.0166767

TLR3 toll-like receptor 3 1.282615 0.01532234

FHL1 four and a half LIM domains 1 1.282345 0.00644461 CNK5 potassium channel, subfamily K, member 5 1.282262 0.0289603

PLAC4 placenta-specific 4 1.282113 0.01069166 guanylate cyclase 2C (heat stable enterotoxin

GUCY2C receptor) 1.281951 0.01787448

CABIN 1 calcineurin binding protein 1 1.28167 0.03449354

BMF Bcl2 modifying factor 1.281669 0.01524191

CCDC68 coiled-coil domain containing 68 1.281411 0.04189215

DYM dymeclin 1.281358 0.03128598

ZNF804B zinc finger protein 804B 1.281045 0.01404671

Clorf228 chromosome 1 open reading frame 228 1.280803 0.01893027 pro-platelet basic protein (chemokine (C-X-C

PPBP motif) ligand 7) 1.280777 0.01782109 XCL1 chemokine (C motif) ligand 1 1.280574 0.04413665 translocase of outer mitochondrial membrane

TOMM40L 40 homolog (yeast)-like 1.280371 0.02338092

RASGEFIC RasGEF domain family, member 1C 1.280162 0.0280827

JPH4 junctophilin 4 1.28015 0.04280613 family with sequence similarity 54, member

FAM54A A 1.279955 0.03734787 potassium channel tetramerisation domain

KCTD5 containing 5 1.27975 0.02869465

Olfactory receptor, family 13, subfamily C,

OR13C2 member 2 1.279711 0.03442259

ZC3H18 zinc finger CCCH-type containing 18 1.27964 0.04636705

CAPN10 calpain 10 1.279257 0.00198792

ING5 inhibitor of growth family, member 5 1.27892 0.04661732

RGS8 regulator of G-protein signaling 8 1.278832 0.00174233

AC02 aconitase 2, mitochondrial 1.27882 0.04484345

FKBP10 FK506 binding protein 10, 65 kDa 1.278655 0.0175814

Olfactory receptor, family 6, subfamily C,

OR6C3 member 3 1.278611 0.01752476

RCAN2 regulator of calcineurin 2 1.278387 0.03588298

PGCP plasma glutamate carboxypeptidase 1.2781 0.01883749

TERT telomerase reverse transcriptase 1.278023 0.01279226

ADAM28 ADAM metallopeptidase domain 28 1.277873 0.00355689 fibroblast growth factor 9 (glia-activating

FGF9 factor) 1.277817 0.03562992 SIGLEC7 sialic acid binding Ig-like lectin 7 1.277801 0.04178277

DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

CD300A CD300a molecule 1.27763 0.01498091

FRMD3 FERM domain containing 3 1.277627 0.01554986

Cl lorf39 chromosome 11 open reading frame 39 1.277453 0.00448246

KIAA1772 IAA1772 1.277126 0.03375901 wingless-type MMTV integration site family,

W T5B member 5B 1.27708 0.0226936

HHATL hedgehog acyltransferase-like 1.277057 0.04379471

MDC1 mediator of DNA-damage checkpoint 1 1.277011 0.03028642

DDR2 discoidin domain receptor tyrosine kinase 2 1.276973 0.03395236

Rap guanine nucleotide exchange factor

RAPGEF1 (GEF) 1 1.276884 0.01192098

ELK3, ETS-domain protein (SRF accessory

ELK3 protein 2) 1.276704 0.00360868

CFH complement factor H 1.276522 0.01729259

KIF6 Kinesin family member 6 1.275939 0.00729677

PALLD palladin, cytoskeletal associated protein 1.275797 0.00096629

ZNF512 zinc finger protein 512 1.275728 0.04504732 aldehyde dehydrogenase 16 family, member

ALDH16A1 Al 1.275703 0.04010194

WDR23 WD repeat domain 23 1.275664 0.00341463

SLC47A1 solute carrier family 47, member 1 1.275285 0.04228358

CCDC132 coiled-coil domain containing 132 1.275185 0.02473214

IMPACT Impact homolog (mouse) 1.275025 0.03467059

HPSE heparanase 1.274968 0.03689874

LHX6 LIM homeobox 6 1.274965 0.01865077 major facilitator superfamily domain

MFSD8 containing 8 1.27465 0.02330326 osteoclast associated, immunoglobulin-like

OSCAR receptor 1.27438 0.02518541

BMP2K BMP2 inducible kinase 1.274379 0.04885737

Olfactory receptor, family 8, subfamily S,

OR8S1 member 1 1.274174 0.03604905

ZNF329 Zinc finger protein 329 1.274083 0.04612534

GATA5 GATA binding protein 5 1.273996 0.00282524

FHL2 four and a half LIM domains 2 1.273898 0.00514596 polycystic kidney disease 1 (autosomal

PKD1 dominant) 1.273857 0.00447694

WDR33 WD repeat domain 33 1.273789 0.00149716

KIAA0831 KIAA0831 1.273734 0.04652461

SP110 SP110 nuclear body protein 1.273585 0.00042015

STIM2 stromal interaction molecule 2 1.273451 0.02757475

CNPY4 canopy 4 homolog (zebrafish) 1.273357 8.71E-05

N-acylsphingosine amidohydrolase (acid

ASAH1 ceramidase) 1 1.273185 0.03366104

GYPB glycophorin B (M S blood group) 1.273166 0.00262253 origin recognition complex, subunit 1-like

ORC1L (yeast) 1.273124 0.03331651

FES feline sarcoma oncogene 1.273069 0.04620132

CNGB1 cyclic nucleotide gated channel beta 1 1.272862 0.0377707

VPS13D vacuolar protein sorting 13 homolog D (S. 1.272795 0.0243252

>B1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value cerevisiae)

NAPSA napsin A aspartic peptidase 1.272758 0.03131851

EPB41L3 Erythrocyte membrane protein band 4.1 -like 3 1.272611 0.03658226

ANKRD23 ankyrin repeat domain 23 1.272549 0.02940823

PFTK1 PFTAIRE protein kinase 1 1.272423 0.01977383 budding uninhibited by benzimidazoles 1

BUB1 homolog (yeast) 1.272392 0.01439459 calcium channel, voltage-dependent, T type,

CACNA1G alpha 1G subunit 1.27238 0.03676087 solute carrier family 7 (cationic amino acid

SLC7A7 transporter, y+ system), member 7 1.272137 0.00085848

FLJ43826 FLJ43826 protein 1.271965 0.03776522

DAP3 death associated protein 3 1.271808 0.02339598 ral guanine nucleotide dissociation stimulator¬

RGL2 like 2 1.271306 0.0133294

SEC16B SEC 16 homolog B (S. cerevisiae) 1.27129 0.01950576 caspase 10, apoptosis-related cysteine

C ASP 10 peptidase 1.271252 0.01758932

SEPP1 selenoprotein P, plasma, 1 1.271193 0.01057495 interleukin 16 (lymphocyte chemoattractant

IL16 factor) 1.270979 0.03838038

KRT222P Keratin 222 pseudogene 1.270266 0.01755372

DOCK9 dedicator of cytokinesis 9 1.270219 0.03743694

ZNF45 zinc finger protein 45 1.269929 0.00158253

CTNNA3 Catenin (cadherin-associated protein), alpha 3 1.269856 0.01638294

C20orfl2 chromosome 20 open reading frame 12 1.269786 0.02471881

PLXNA2 plexin A2 1.269566 0.02525014

MAMDC4 MAM domain containing 4 1.269402 0.03698598

CCDC13 coiled-coil domain containing 13 1.269384 0.04620048

SH2D3A SH2 domain containing 3A 1.26919 0.04955038

ZNF233 zinc finger protein 233 1.269046 0.04749038

ZNF187 zinc finger protein 187 1.269039 0.04979211

XP04 exportin 4 1.268991 0.02555127

LIG1 ligase I, DNA, ATP-dependent 1.268785 0.01252088 platelet-activating factor acetylhydrolase lb,

PAFAH1B3 catalytic subunit 3 (29kDa) 1.268768 0.02361777

BRD9 bromodomain containing 9 1.268707 0.03008722

NLRC4 NLR family, CARD domain containing 4 1.268671 0.04980405

PAK1IP1 PAK1 interacting protein 1 1.26866 0.0392548

ARMCX4 Armadillo repeat containing, X-linked 4 1.268576 0.04715846

C9orf96 chromosome 9 open reading frame 96 1.268235 0.04998496 protein tyrosine phosphatase, non-receptor

PTPN3 type 3 1.268219 0.00406255

GPR87 G protein-coupled receptor 87 1.268184 0.0186203

EFNA3 ephrin-A3 1.268123 0.00940622 discs, large (Drosophila) homolog-associated

DLGAP1 protein 1 1.268032 0.02595138

WDFY4 WDFY family member 4 1.267986 0.03854549

PF4 platelet factor 4 1.267797 0.00548331

ERC2 ELKS/RAB6-interacting/CAST family 1.267697 0.00443263

DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value member 2

PRP38 pre-mR A processing factor 38

PRPF38A (yeast) domain containing A 1.267458 0.0372219 phosphoinositide-3 -kinase, catalytic, delta

P1K3CD polypeptide 1.267128 0.03911769

C19orf34 chromosome 19 open reading frame 34 1.266845 0.00685461

ITFG1 integrin alpha FG-GAP repeat containing 1 1.266819 0.01601937

Olfactory receptor, family 8, subfamily B,

OR8B12 member 12 1.266802 0.04584406

Olfactory receptor, family 5, subfamily K,

OR5K2 member 2 1.266728 0.02286792

ANK3 ankyrin 3, node of Ranvier (ankyrin G) 1.266635 0.00897063

NXF4 nuclear RNA export factor 4 pseudogene 1.266614 0.04825277

TRAF1 TNF receptor-associated factor 1 1.266585 0.00887076

ANKH ankylosis, progressive homolog (mouse) 1.266464 0.01 161282 xylosylprotein beta 1,4-galactosyltransferase,

B4GALT7 polypeptide 7 (galactosyltransferase I) 1.266262 0.03999451

FBX025 F-box protein 25 1.26606 0.00840386

TMX2 thioredoxin-related transmembrane protein 2 1.266034 0.04371312

C6orfl36 chromosome 6 open reading frame 136 1.265831 0.04085107

IGK@ immunoglobulin kappa locus 1.265694 0.03342056

C15orf42 chromosome 15 open reading frame 42 1.265572 0.00284937

TBCD tubulin folding cofactor D 1.265504 0.04275692

MRPL37 mitochondrial ribosomal protein L37 1.265484 0.03009753 excision repair cross-complementing rodent

repair deficiency, complementation group 1

ERCC1 (includes overlapping antisense sequence) 1.265089 0.0424201 1

FLT4 fms-related tyrosine kinase 4 1.265003 0.03423229

TRIM5 tripartite motif-containing 5 1.264801 0.02508482

REG1P regenerating islet-derived 1 pseudogene 1.264619 0.00304221

NCRNAOOIO

5 non-protein coding RNA 105 1.264585 0.03283363

NCOR1 nuclear receptor co-repressor 1 1.264318 0.04431849 TGFBR3 transforming growth factor, beta receptor III 1.264265 0.00830997 leucine-rich repeats and death domain

LRDD containing 1.26396 0.04144039 RTAP17-1 keratin associated protein 17-1 1.26364 0.02127454

SLC26A8 Solute carrier family 26, member 8 1.263636 0.00328375

KIAA1199 KIAA1 199 1.263474 0.00299676

GOLGA1 golgin Al 1.263419 0.01217355 bromodomain and WD repeat domain

BRWD3 containing 3 1.263346 0.00890564

TBRG1 transforming growth factor beta regulator 1 1.263335 0.04770941

SURF1 surfeit 1 1.263306 0.03347953

CD6 CD6 molecule 1.263225 0.03078951

KLHL2 kelch-like 2, Mayven (Drosophila) 1.263015 0.04091952

TRAJ17 T cell receptor alpha joining 17 1.263008 0.03624336

PLK3 polo-like kinase 3 (Drosophila) 1.262955 0.03572863

SST somatostatin 1.262923 0.04839899

SFXN1 sideroflexin 1 1.262718 0.02940824

DB l/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

SWI/SNF related, matrix associated, actin

dependent regulator of chromatin, subfamily

SMARCD3 d, member 3 1.26252 0.03847378

SEZ6L Seizure related 6 homolog (mouse)-like 1.262417 0.03785276

Cl lorf45 chromosome 11 open reading frame 45 1.262314 0.04663807

ATPase, H+ transporting, lysosomal 38kDa,

ATP6V0D2 V0 subunit d2 1.262176 0.04861804

DTNB dystrobrevin, beta 1.262109 0.03182453

SLIT2 slit homolog 2 (Drosophila) 1.261927 0.03785233

DEFA3 defensin, alpha 3, neutrophil-specific 1.261861 0.00224643

CDH16 cadherin 16, KSP-cadherin 1.261774 0.04225288

OXCT1 3-oxoacid CoA transferase 1 1.261625 0.02520766

RILPL2 Rab interacting lysosomal protein-like 2 1.261574 0.04999934 squamous cell carcinoma antigen recognized

SART3 by T cells 3 1.261361 0.02103018

NIMA (never in mitosis gene a)- related

NEK11 kinase 11 1.261331 0.00276633

ASB3 ankyrin repeat and SOCS box-containing 3 1.260703 0.01934422

AASS aminoadipate-semialdehyde synthase 1.260648 0.0152571

DCDC5 doublecortin domain containing 5 1.260575 0.03489532 leukocyte immunoglobulin-like receptor

LILRP2 pseudogene 2 1.26038 0.02068243

LAP3 leucine aminopeptidase 3 1.260347 0.04343932

CCDC81 coiled-coil domain containing 81 1.260205 0.02935852

HPX hemopexin 1.26013 0.03974206

LCT lactase 1.260111 0.04553083 inhibitor of DNA binding 1, dominant

ID1 negative helix-loop-helix protein 1.259904 0.02807979 protein phosphatase 2, regulatory subunit A,

PPP2R1A alpha 1.25989 0.02451023

FLT3LG fms-related tyrosine kinase 3 ligand 1.259681 0.02655841 solute carrier organic anion transporter

SLC01C1 family, member 1C1 1.259636 0.01324903

SBN02 strawberry notch homolog 2 (Drosophila) 1.259623 0.00161167

DENND4A DENN/MADD domain containing 4A 1.259615 0.01542732

FBX04 F-box protein 4 1.259492 0.0287693

MYOIA myosin IA 1.259388 0.02597957

AGXT2L2 alanine-glyoxylate aminotransferase 2-like 2 1.259298 0.02693991

C3orf58 chromosome 3 open reading frame 58 1.259091 0.04608467

MAGEA3 melanoma antigen family A, 3 1.259048 0.00534565

ABHD5 abhydrolase domain containing 5 1.259035 0.00596344

AU RNA binding protein/enoyl-CoA

AUH hydratase 1.259026 0.00182977

ATPase, Ca++ transporting, cardiac muscle,

ATP2A1 fast twitch 1 1.258936 0.03883481

HTATIP2 HIV-1 Tat interactive protein 2, 30kDa 1.258927 0.00915241

Cl lorf65 chromosome 11 open reading frame 65 1.258777 0.03677547 sema domain, transmembrane domain (TM),

SEMA6D and cytoplasmic domain, (semaphorin) 6D 1.258565 0.01420403

RARRES1 retinoic acid receptor responder (tazarotene 1.258483 0.04067531

DB1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value induced) 1

WSCD1 WSC domain containing 1 1.258403 0.00833534

PDE8A phosphodiesterase 8A 1.258003 0.01337859

FLJ46020 FLJ46020 protein 1.257828 0.04452509

UDP-N-acetyl-alpha-D- galactosamine:polypeptide N- acetylgalactosaminyltransferase 2 (GalNAc-

GALNT2 T2) 1.257702 0.02625265

P antigen family, member 5 (prostate

PAGE5 associated) 1.257566 0.01814344

ARSE arylsulfatase E (chondrodysplasia punctata 1) 1.257193 0.04391929

ELN elastin 1.257191 0.01340862

RBKS ribokinase 1.256993 0.0264602 signal transducer and activator of

STAT4 transcription 4 1.25671 0.03391 138

NLRP8 NLR family, pyrin domain containing 8 1.256625 0.01782726

DEAD/H (Asp-Glu-Ala-Asp/His) box

DDX26B polypeptide 26B 1.256569 0.03026909

RADIL Ras association and DIL domains 1.256547 0.04544739

NT5C1A 5'-nucleotidase, cytosolic IA 1.256494 0.03504009

CUGBP1 CUG triplet repeat, RNA binding protein 1 1.256281 0.01282044

SVIL supervillin 1.256071 0.02925793

COL25A1 collagen, type XXV, alpha 1 1.256013 0.02472257

QSOX1 quiescin Q6 sulfhydryl oxidase 1 1.255929 0.04328222

RPL13AP3 N/A 1.255772 0.04531485 reversion-inducing-cysteine-rich protein with

RECK kazal motifs 1.255739 0.03604279

KIFC2 kinesin family member C2 1.25571 0.03033769

WDR21A WD repeat domain 21 A 1.255693 0.03791939

WD repeat domain, phosphoinositide

WIPI1 interacting 1 1.255604 0.01893768

TP53TG3 //

LOC729355 N/A 1.255549 0.0020767

Olfactory receptor, family 5, subfamily A,

OR5A2 member 2 1.255506 0.01179942

Protein tyrosine phosphatase, non-receptor

PTPN20B type 20B 1.255418 0.00627889

DDIT4 DNA-damage-inducible transcript 4 1.255402 0.025832 potassium voltage-gated channel, subfamily H

KCNH7 (eag-related), member 7 1.255352 0.02113436

NPFFR2 neuropeptide FF receptor 2 1.255223 0.04185481 potassium voltage-gated channel, shaker-

KCNAB1 related subfamily, beta member 1 1.254744 0.01451986

MYOF myoferlin 1.254717 0.00140488

KIF21A kinesin family member 21 A 1.254658 0.04178249

BST2 bone marrow stromal cell antigen 2 1.254582 0.04913527

ANKRD6 ankyrin repeat domain 6 1.254334 0.03832837

NPTN neuroplastin 1.25423 0.03097989

TMC06 transmembrane and coiled-coil domains 6 1.25402 0.02030981

C6orfl70 chromosome 6 open reading frame 170 1.253451 0.02398408

Bl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

C5orfl7 Chromosome 5 open reading frame 17 1.253056 0.04253337 C10orfl l9 chromosome 10 open reading frame 119 1.25289 0.02257121

TAF1 RNA polymerase II, TATA box

binding protein (TBP)-associated factor,

TAF1L 210kDa-like 1.252848 0.00267541 DLX1 Distal-less homeobox 1 1.252657 0.02709251

CATSPERB cation channel, sperm-associated, beta 1.252615 0.02413714

ATP-binding cassette, sub-family C

ABCC11 (CFTR/MRP), member 11 1.252585 0.03516509 sodium channel, voltage-gated, type I, alpha

SCN1A subunit 1.252542 0.03944445 cystatin 8 (cystatin-related epididymal

CST8 specific) 1.252505 0.0416996 CD 109 CD 109 molecule 1.252274 0.03737299 UNQ6484 N/A 1.252122 0.04830452 PCDH20 Protocadherin 20 1.251784 0.04956578 PHF17 PHD finger protein 17 1.25171 0.00222868 missing oocyte, meiosis regulator, homolog

MIOS (Drosophila) 1.25141 0.01816732 MFN1 mitofusin 1 1.251298 0.03838396 ZNF615 zinc finger protein 615 1.251296 0.00735893 solute carrier family 29 (nucleoside

SLC29A3 transporters), member 3 1.251202 0.04813668

NELL1 NEL-like 1 (chicken) 1.251 108 0.03206594

RBM8A RNA binding motif protein 8 A 1.250975 0.00571058

ZNF34 Zinc finger protein 34 1.250962 0.04253855

CRABP2 cellular retinoic acid binding protein 2 1.250729 0.02425808

TMEM116 transmembrane protein 116 1.250651 0.02323204

TMEM19 transmembrane protein 19 1.250607 0.02521007

HSDL2 hydroxysteroid dehydrogenase like 2 1.250353 0.0421 1176

CLDN9 claudin 9 1.25029 0.03369131

HYOU1 hypoxia up-regulated 1 1.250242 0.04870764

TBC1D19 TBC1 domain family, member 19 1.250161 0.02438511

FOXR1 forkhead box Rl 1.250011 0.03306343

TM6SF2 transmembrane 6 superfamily member 2 1.249824 0.04033987

BEST3 bestrophin 3 1.249729 0.04319492 polymerase (RNA) III (DNA directed)

POLR3E polypeptide E (80kD) 1.249658 0.02249824

Sodium channel, voltage-gated, type VII,

SCN7A alpha 1.249531 0.01527615 nudix (nucleoside diphosphate linked moiety

NUDT21 X)-type motif 21 1.249476 0.04665571 COL4A4 collagen, type IV, alpha 4 1.249356 0.00608043 NPAS3 neuronal PAS domain protein 3 1.249345 0.03665376 cell adhesion molecule with homology to

CHLl LI CAM (close homolog of LI) 1.249314 0.04459813

MTMR4 myotubularin related protein 4 1.249254 0.03144312

MYOZ2 myozenin 2 1.249074 0.00446696

IER2 immediate early response 2 1.248976 0.02301345

YRDC yrdC domain containing (E. coli) 1.248842 0.03258699 1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

C10orf79 chromosome 10 open reading frame 79 1.248821 0.00924585

PSEN1 presenilin 1 1.24867 0.03671699

C5 complement component 5 1.248575 0.02374031

ACCN4 amiloride-sensitive cation channel 4, pituitary 1.248535 0.03166102 AKAP10 A kinase (PRKA) anchor protein 10 1.248322 0.0276429 PER3 period homolog 3 (Drosophila) 1.247536 0.03416167 CYTSA cytospin A 1.247512 0.01152395

5-hydroxytryptamine (serotonin) receptor 3,

HTR3E family member E 1.247383 0.04654415 TGDS TDP-glucose 4,6-dehydratase 1.247366 0.03307131 RPLPO ribosomal protein, large, P0 1.247362 0.01263738 CDH7 cadherin 7, type 2 1.247353 0.02363331

S1 3 homolog B, transcription regulator

SIN3B (yeast) 1.247232 0.0053172

ATP10D ATPase, class V, type 10D 1.247181 0.00263839

MED22 mediator complex subunit 22 1.24695 0.02500488 myeloid/lymphoid or mixed-lineage leukemia

(trithorax homolog, Drosophila); translocated

MLLT6 to, 6 1.246925 0.02638247 general transcription factor IIIC, polypeptide

GTF3C5 5, 63kDa 1.246715 0.02038165

LAMA1 Laminin, alpha 1 1.246648 0.03326858

EXOSC2 exosome component 2 1.246267 0.04580224

KIAA1524 KIAA1524 1.24618 0.02323518

EMP3 epithelial membrane protein 3 1.246123 0.04739262

ACTR8 ARP8 actin-related protein 8 homolog (yeast) 1.245862 0.04051028

PTPRA protein tyrosine phosphatase, receptor type, A 1.24583 0.00032856

C9or 7 Chromosome 9 open reading frame 97 1.245606 0.04273148

LRRC56 leucine rich repeat containing 56 1.245143 0.02420723

StAR-related lipid transfer (START) domain

STARD8 containing 8 1.244687 0.01282923 ZNF417 Zinc finger protein 417 1.244519 0.01805726 cytochrome P450, family 11, subfamily B,

CYP11B2 polypeptide 2 1.244442 0.00970924

C17orfl01 chromosome 17 open reading frame 101 1.244439 0.00858935

KHSRP KH-type splicing regulatory protein 1.244419 0.018

SCGB1C1 secretoglobin, family 1C, member 1 1.244323 0.01092525

TMEM117 transmembrane protein 117 1.24416 0.02746787

UBA7 ubiquitin-like modifier activating enzyme 7 1.243926 0.04828025

GYG2 glycogenin 2 1.243761 0.03227631

MYBPH myosin binding protein H 1.243565 0.00017673

ILF3 interleukin enhancer binding factor 3, 90kDa 1.243423 0.02255549

RIGS Rho GTPase-activating protein 1.243378 0.03389494

SIGLEC10 sialic acid binding Ig-like lectin 10 1.243329 0.00809374 STRN4 striatin, calmodulin binding protein 4 1.243233 0.02055198 sodium channel, voltage-gated, type IX, alpha

SCN9A subunit 1.243131 0.00576424 MDFIC MyoD family inhibitor domain containing 1.242969 0.03261241 NPHP1 nephronophthisis 1 (juvenile) 1.242624 0.0094737 BAIAP2L2 BAI1 -associated protein 2-like 2 1.242568 0.02808724

DB1/ 69₄37516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

RTTN rotatin 1.242297 0.03280613

R F26 ring finger protein 26 1.242143 0.04297931

GYLTL1B glycosyltransferase-like IB 1.241949 0.03596241

PEX19 peroxisomal biogenesis factor 19 1.241849 0.03167719

MYLK2 myosin light chain kinase 2 1.241836 0.03570873

PRDM11 PR domain containing 1 1 1.241577 0.027784

SLC44A5 solute carrier family 44, member 5 1.241513 0.02358223

POLR1A polymerase (RNA) I polypeptide A, 194kDa 1.241458 0.0372547

NFASC neurofascin homolog (chicken) 1.241441 0.04145633

KIAA1609 KIAA1609 1.24138 0.02715623

CNTN4 Contactin 4 1.241357 0.04543522

PQLC2 PQ loop repeat containing 2 1.241309 0.01358148

CCDC83 coiled-coil domain containing 83 1.24103 0.04831954

MFAP5 microfibrillar associated protein 5 1.240745 0.04278633

NEURL4 neuralized homolog 4 (Drosophila) 1.240582 0.00550729

5-hydroxytryptamine (serotonin) receptor 7

HTR7 (adenylate cyclase-coupled) 1.239826 0.00939692

AI CF APOBEC1 complementation factor 1.239591 0.00588546 family with sequence similarity 1 14, member

FAM1 14A1 Al 1.239459 0.01022173

FOXL2 forkhead box L2 1.239076 0.01996097

TRIM39 tripartite motif-containing 39 1.239033 0.02655088

AMDHD1 amidohydrolase domain containing 1 1.238857 0.0060976

CLSTN3 calsyntenin 3 1.238825 0.02663447

CRIPT cysteine-rich PDZ-binding protein 1.238761 0.0415393

SERHL Serine hydrolase-like 1.238545 0.03856226

INHBB inhibin, beta B 1.238504 0.00822597

SAMD3 sterile alpha motif domain containing 3 1.238401 0.01760916

YAF2 YY1 associated factor 2 1.238376 0.03121256

HERC3 hect domain and RLD 3 1.238202 0.01 12952

IL1F7 interleukin 1 family, member 7 (zeta) 1.238071 0.03715499

SFTPD surfactant protein D 1.238055 0.02607706

UTP18, small subunit (SSU) processome

UTP18 component, homolog (yeast) 1.23789 0.01561913 serine peptidase inhibitor-like, with Kunitz

SPINLW1 and WAP domains 1 (eppin) 1.237717 0.03300332

TPH2 tryptophan hydroxylase 2 1.237646 0.04347964

SNX8 sorting nexin 8 1.237644 0.0299587

CCNK cyclin K 1.237567 0.03657386

CYTH4 cytohesin 4 1.237449 0.04776589

TEAD4 TEA domain family member 4 1.237242 0.03223393

HKDC1 Hexokinase domain containing 1 1.237239 0.014991

ZBTB32 zinc finger and BTB domain containing 32 1.237223 0.00738703

LRRC25 leucine rich repeat containing 25 1.237094 0.0317678

ADCY10 adenylate cyclase 10 (soluble) 1.23699 0.02988935

MBD3L2 Methyl-CpG binding domain protein 3-like 2 1.236936 0.03597342

CCDC110 coiled-coil domain containing 110 1.236882 0.03089214

NCRNA0016

1 non-protein coding RNA 161 1.236863 0.04879846

CYP11A1 cytochrome P450, family 11, subfamily A, 1.236533 0.0107929

⁾B1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value polypeptide 1

FAAH2 fatty acid amide hydrolase 2 1.236528 0.04272511

SYMPK symplekin 1.236523 0.00753091

NLRP14 NLR family, pyrin domain containing 14 1.235995 0.02067863

SPATA13 spermatogenesis associated 13 1.235982 0.01841387

FLJ14100 hypothetical protein FLJ14100 1.235981 0.01346477

BMS1P5 BMS1 pseudogene 5 1.235944 0.02398758

ZNF428 zinc finger protein 428 1.235923 0.02032021

GALNAC4S-

6ST B cell RAG associated protein 1.235856 0.00316015

TNRC6A trinucleotide repeat containing 6A 1.235851 0.04134624 nuclear receptor subfamily 2, group F,

NR2F1 member 1 1.235843 0.04550788 TMC3 transmembrane channel-like 3 1.235688 0.00186255 IL4R interleukin 4 receptor 1.235665 0.0349981 ribonuclease L (2',5'-oligoisoadenylate

RNASEL synthetase-dependent) 1.235518 0.02035331

PRELID2 PRELI domain containing 2 1.235512 0.04554335

PCNX pecanex homolog (Drosophila) 1.235013 0.04108437

ZNF79 zinc finger protein 79 1.235001 0.04024746

PLXNA1 plexin Al 1.234965 0.04264428

METTL13 methyltransferase like 13 1.234935 0.01797137

CGN cingulin 1.234766 0.04962725

BTB and CNC homology 1 , basic leucine

BACH1 zipper transcription factor 1 1.234722 0.01598341 GADL1 glutamate decarboxylase-like 1 1.234581 0.03999796

G protein-coupled receptor, family C, group

GPRC6A 6, member A 1.234368 0.03671451 OTX1 orthodenticle homeobox 1 1.234312 0.03872799 adaptor-related protein complex 1 , sigma 2

AP1S2 subunit 1.234244 0.04050856 Clorfl62 chromosome 1 open reading frame 162 1.233765 0.04205373 GIMAP8 GTPase, IMAP family member 8 1.233485 0.04245494 PRKCE protein kinase C, epsilon 1.233257 0.02306676 aldo-keto reductase family 1 , member C2

(dihydrodiol dehydrogenase 2; bile acid

binding protein; 3 -alpha hydroxy steroid

AKR1C2 dehydrogenase, type III) 1.232654 0.03067469 upper zone of growth plate and cartilage

UCMA matrix associated 1.232605 0.0148044

FLJ26850 FLJ26850 protein 1.232564 0.00472674

PTDSS2 phosphatidylserine synthase 2 1.232397 0.01211942

LAPTM5 lysosomal protein transmembrane 5 1.232132 0.04167828

E2F8 E2F transcription factor 8 1.232086 0.00048585

AMY1A amylase, alpha 1A (salivary) 1.231974 0.03097984

BBS9 Bardet-Biedl syndrome 9 1.231838 0.04666133 butyrobetaine (gamma), 2-oxoglutarate

dioxygenase (gamma-butyrobetaine

BBOX1 hydroxylase) 1 1.231478 0.01092679 SERHL2 serine hydrolase-like 2 1.231232 0.02799732

DB1/ 69437₅16.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

SERAC1 serine active site containing 1 1.231142 0.04286629

TROAP trophinin associated protein (tastin) 1.231035 0.03471954

DUS3L dihydrouridine synthase 3-like (S. cerevisiae) 1.230713 0.01696831

Ganglioside-induced differentiation-

GDAP1L1 associated protein 1 -like 1 1.230631 0.01765892 solute carrier family 25 (mitochondrial

SLC25A23 carrier; phosphate carrier), member 23 1.230625 0.02786495

PDI 1L PDLIM1 interacting kinase 1 like 1.230556 0.01222398

OTOR otoraplin 1.230331 0.0006035

UPF3 regulator of nonsense transcripts

UPF3A homolog A (yeast) 1.23028 0.0287505 solute carrier family 25 (mitochondrial

SLC25A12 carrier, Aralar), member 12 1.230237 0.014549

LSM7 homolog, U6 small nuclear RNA

LSM7 associated (S. cerevisiae) 1.230163 0.02583374 leukocyte immunoglobulin-like receptor,

subfamily B (with TM and ITIM domains),

LILRB2 member 2 1.229932 0.03151425

DnaJ (Hsp40) homolog, subfamily C, member

DNAJC10 10 1.229817 0.03064105

RASGEF1A RasGEF domain family, member 1 A 1.22916 0.0460017

ZNF679 zinc finger protein 679 1.229125 0.04788786 cholinergic receptor, nicotinic, alpha 1

CHRNAl (muscle) 1.229101 0.01837677 DPYSL5 dihydropyrimidinase-like 5 1.229031 0.01631308 FCHSD1 FCH and double SH3 domains 1 1.229024 0.02041655 NKIRAS1 NFKB inhibitor interacting Ras-like 1 1.228784 0.01403705 steroid-5-alpha-reductase, alpha polypeptide 2

(3-oxo-5 alpha-steroid delta 4-dehydrogenase

SRD5A2 alpha 2) 1.228617 0.01614202 mannosyl (alpha- 1 ,6-)-glycoprotein beta- 1,6-

MGAT5B N-acetyl-glucosaminyltransferase, isozyme B 1.228543 0.00058875 GK 1 gastrokine 1 1.228174 0.00324149

Cas-Br-M (murine) ecotropic retroviral

CBLC transforming sequence c 1.228113 0.0475787

CXorf50B N/A 1.227824 0.00097768

LRRC36 leucine rich repeat containing 36 1.227789 0.04154441

UTS2D urotensin 2 domain containing 1.227373 0.02920385

OPN5 opsin 5 1.227325 0.0068055

PCDHB10 protocadherin beta 10 1.227223 0.04429794

ArfGAP with coiled-coil, ankyrin repeat and

ACAP2 PH domains 2 1.227105 0.03728326

CAP, adenylate cyclase-associated protein, 2

CAP2 (yeast) 1.226974 0.04016996

FHIT fragile histidine triad gene 1.226757 0.04422508

C2CD2 C2 calcium-dependent domain containing 2 1.226726 0.00134391

R3HDM2 R3H domain containing 2 1.226641 0.01355409

AHCYL1 adenosylhomocysteinase-like 1 1.226394 0.00961029

CCL21 chemokine (C-C motif) ligand 21 1.226341 0.00087255

MCM10 minichromosome maintenance complex 1.226335 0.03173039

DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value component 10

myosin, light chain 3, alkali; ventricular,

MYL3 skeletal, slow 1.226334 0.04743267

ZNF14 zinc finger protein 14 1.226214 0.00392558

FLJ44635 TPTl-like protein 1.226008 0.04428207

FOXD3 forkhead box D3 1.226 0.04097072

SWI/SNF related, matrix associated, actin

dependent regulator of chromatin, subfamily

SMARCA1 a, member 1 1.225814 0.02792728

GLTP glycolipid transfer protein 1.225619 0.02234763 v-crk sarcoma virus CT10 oncogene homolog

CRKL (avian)-like 1.22546 0.02004339

FBXL12 F-box and leucine-rich repeat protein 12 1.225415 0.02509421

TRAF5 T F receptor-associated factor 5 1.225339 0.00872158

HOXD11 homeobox Dl 1 1.225316 0.00666115

RAD51L1 RAD51-like 1 (S. cerevisiae) 1.225063 0.03158881 kelch repeat and BTB (POZ) domain

KBTBD3 containing 3 1.225048 0.00868803

LUZP4 leucine zipper protein 4 1.225036 0.01539111

DEAH (Asp-Glu-Ala-His) box polypeptide

DHX34 34 1.224813 0.03617669

CNPY2 canopy 2 homolog (zebrafish) 1.224602 0.04495685

PRP39 pre-mRNA processing factor 39

PRPF39 homolog (S. cerevisiae) 1.22453 0.01035303

ASGR2 asialoglycoprotein receptor 2 1.224014 0.0055253

PRKG1 protein kinase, cGMP-dependent, type I 1.223879 0.04519305 disabled homolog 2, mitogen-responsive

DAB2 phosphoprotein (Drosophila) 1.223839 0.00800414 olfactory receptor, family 5, subfamily H,

OR5H1 member 1 1.223542 0.0050431

SRPK2 SFRS protein kinase 2 1.22325 0.01501723 small nuclear ribonucleoprotein 35kDa

SNR P35 (U11/U12) 1.222875 0.00777022

Olfactory receptor, family 2, subfamily M,

OR2M7 member 7 1.222822 0.03207624

TCOF1 Treacher Collins-Franceschetti syndrome 1 1.222738 0.00826843

ANK2 ankyrin 2, neuronal 1.222676 0.00634497

G2E3 G2/M-phase specific E3 ubiquitin ligase 1.222631 0.00185943 solute carrier family 39 (zinc transporter),

SLC39A6 member 6 1.22186 0.0061314

ZNF425 Zinc finger protein 425 1.221839 0.03781226

POPDC2 popeye domain containing 2 1.221836 0.00725864

KCNE1L KCNEl-like 1.221821 0.01817093

TSC22D2 TSC22 domain family, member 2 1.221814 0.022301 excision repair cross-complementing rodent

ERCC6 repair deficiency, complementation group 6 1.221669 0.02154465 solute carrier family 1 (glutamate transporter),

SLC1A7 member 7 1.221415 0.03713144

ATP-binding cassette, sub-family A (ABCl),

ABCA10 member 10 1.220669 0.00882892

DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Up regulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value pantothenate kinase 1 1.220656 0.01608154 solute carrier family 12 (potassium/chloride

transporters), member 9 1.22038 0.04903245 transmembrane protein 156 1.220203 0.03900463

Ca++-dependent secretion activator 1.219984 0.04382195

SPARC-like 1 (hevin) 1.219852 0.03913905

Sorbin and SH3 domain containing 1 1.219499 0.01097803 tubulin folding cofactor C 1.219283 0.02493064 hyaluronan and proteoglycan link protein 1 1.219148 0.02616776 forkhead box D4 1.219085 0.02737425

COMM domain containing 9 1.218971 0.03277739 lymphocyte antigen 9 1.218677 0.04751694 lysyl oxidase-like 3 1.218312 0.02203561 tudor domain containing 9 1.218186 0.0036461

Gardner-Rasheed feline sarcoma viral (v-fgr)

oncogene homolog 1.218069 0.00514118 mucin 13, cell surface associated 1.218026 0.01253442

F-box and leucine-rich repeat protein 13 1.217916 0.00963049 zinc finger, DHHC-type containing 15 1.217781 0.00404771 kinesin family member 2B 1.217704 0.0006307 melanoma antigen family D, 4 1.217564 0.02132055 microsomal triglyceride transfer protein 1.217075 0.04306468 chromosome 1 open reading frame 109 1.216927 0.03071822

N-acylaminoacyl-peptide hydrolase 1.21679 0.04407907

THO complex 4 1.216787 0.0403008

MMS19 nucleotide excision repair homolog

(S. cerevisiae) 1.216589 0.03922461 receptor (TNFRSF)-interacting serine- threonine kinase 1 1.216346 0.01773695

MCF.2 cell line derived transforming

sequence-like 2 1.216222 0.03044115 neogenin homolog 1 (chicken) 1.216163 0.03251328

Hypothetical LOC442092 1.215765 0.01544065 centrosomal protein 1 lOkDa 1.215556 0.03730905 potassium voltage-gated channel, KQT-like

subfamily, member 3 1.215354 0.03121697 oxoeicosanoid (OXE) receptor 1 1.215246 0.02868055 forkhead box J2 1.214929 0.04716483 tripartite motif-containing 31 1.214792 0.04103994 proteasome (prosome, macropain) 26 S

subunit, non-ATPase, 13 1.214569 0.00673002

Solute carrier family 35, member E2 1.214523 0.03901927 alcohol dehydrogenase IB (class I), beta

polypeptide 1.214395 0.00100821

Microtubule associated serine/threonine

kinase family member 4 1.214111 0.0028083 fibrous sheath interacting protein 1 1.213903 0.04737353 zinc finger CCCH-type containing 14 1.213594 0.01712715 xin actin-binding repeat containing 2 1.213568 0.03649298 dynein, axonemal, heavy chain 8 1.213317 0.01764265 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value sortilin-related VPS 10 domain containing

SORCS1 receptor 1 1.213159 0.03788062

RAS guanyl releasing protein 2 (calcium and

RASGRP2 DAG-regulated) 1.21309 0.01101469 vacuolar protein sorting 13 homolog C (S.

VPS 13C cerevisiae) 1.213066 0.03233575

GSDMB gasdermin B 1.212917 0.02996031 carbamoyl-phosphate synthase 1 ,

CPS1 mitochondrial 1.21283 0.04907995

FLJ10404 Hypothetical protein FLJ 10404 1.212673 0.00191574

PHF16 PHD finger protein 16 1.212564 0.01756385

C8orf78 chromosome 8 open reading frame 78 1.212201 0.02255807

MEP1A meprin A, alpha (PABA peptide hydrolase) 1.211724 0.04853678

ADCY1 adenylate cyclase 1 (brain) 1.211412 0.02100712

TSPAN12 tetraspanin 12 1.211375 0.02651059 potassium voltage-gated channel, KQT-like

CNQ4 subfamily, member 4 1.211356 0.0320885

ATPase, H+ transporting, lysosomal

ATP6V1H 50/57kDa, VI subunit H 1.21 1331 0.026815 caspase 8, apoptosis-related cysteine

CASP8 peptidase 1.211198 0.01464514

RNF141 ring finger protein 141 1.211196 0.02991816 ectonucleotide

ENPP2 pyrophosphatase/phosphodiesterase 2 1.211 162 0.0425432

HINT1 histidine triad nucleotide binding protein 1 1.210712 0.04891515

C8orfl7 chromosome 8 open reading frame 17 1.210297 0.04478836 sphingomyelin phosphodiesterase 3, neutral

SMPD3 membrane (neutral sphingomyelinase II) 1.210189 0.04469751

COL6A2 collagen, type VI, alpha 2 1.210041 0.0485979

ZAN zonadhesin 1.209973 0.039782 transmembrane (C -terminal) protease, serine

TMPRSS12 12 1.209923 0.00684086

CALN1 calneuron 1 1.209429 0.03581015

RAGE renal tumor antigen 1.209223 0.0471772

FOLR1 folate receptor 1 (adult) 1.209123 0.04577546

PCSK9 Proprotein convertase subtilisin/kexin type 9 1.209005 0.00561032

LZTFL1 leucine zipper transcription factor-like 1 1.208827 0.03900355

FLJ41327 FLJ41327 protein 1.208808 0.01584038 protein phosphatase, EF-hand calcium

PPEF1 binding domain 1 1.208483 0.00013434

MAPK1 mitogen-activated protein kinase 1 1.208451 0.02953756

X-ray repair complementing defective repair

XRCC2 in Chinese hamster cells 2 1.208432 0.04292725

SCNN1D sodium channel, nonvoltage-gated 1 , delta 1.208383 0.02079827

CEP250 centrosomal protein 250kDa 1.208013 0.0236764

OPTN Optineurin 1.207919 0.00521899

PCTK2 PCTAIRE protein kinase 2 1.207796 0.02335376

ZNF619 zinc finger protein 619 1.207776 0.04679568

OSBP2 oxysterol binding protein 2 1.207761 0.01456842

CCDC84 coiled-coil domain containing 84 1.207745 0.03929433

>B1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

GPR112 G protein-coupled receptor 112 1.207628 0.00260127

RRAGC Ras-related GTP binding C 1.207521 0.03659237

KLK8 kallikrein-related peptidase 8 1.207414 0.01697536

GYS1 glycogen synthase 1 (muscle) 1.207255 0.0073425

RTN1 reticulon 1 1.207216 0.0192233

PAK3 p21 protein (Cdc42/Rac)-activated kinase 3 1.207161 0.04030197 obscurin, cytoskeletal calmodulin and titin-

OBSCN interacting RhoGEF 1.206772 0.02149618

TEX28 testis expressed 28 1.206549 0.04484958

ANKRD29 ankyrin repeat domain 29 1.206277 0.02225841 phosphatidylinositol transfer protein,

PITPNM1 membrane-associated 1 1.20625 0.04758375

X , Kell blood group complex subunit-

XKR3 related family, member 3 1.205822 0.04528149

ZNF528 zinc finger protein 528 1.205598 0.02553913 doublesex and mab-3 related transcription

DMRT2 factor 2 1.205569 0.01802004

MEP1B meprin A, beta 1.205569 0.00113685

SH3 -domain GRB2-like (endophilin)

SGIP1 interacting protein 1 1.205394 0.03094877

IGSF9 immunoglobulin superfamily, member 9 1.205277 0.02384311

IGH@ immunoglobulin heavy locus 1.205258 0.01282709

TBL2 transducin (beta)-like 2 1.205045 0.04332468 general transcription factor IIH, polypeptide

GTF2H3 3, 34kDa 1.204669 0.0151408

MCOLN3 mucolipin 3 1.204651 0.00181367 minichromosome maintenance complex

MCM3 component 3 1.204643 0.02501993

TRIM16 tripartite motif-containing 16 1.204583 0.02110382

RHOBTB1 Rho-related BTB domain containing 1 1.204574 0.0231 1136

TSNARE1 t-SNARE domain containing 1 1.204487 0.00549102

Caspase 14, apoptosis-related cysteine

CASP14 peptidase 1.204455 0.02818916

CDH26 cadherin 26 1.204397 0.01957364

TTLL7 tubulin tyrosine ligase-like family, member 7 1.204374 0.00056749

EDA ectodysplasin A 1.203475 0.04743863 olfactory receptor, family 2, subfamily T,

OR2T27 member 27 1.203472 0.01128284

TAF12 RNA polymerase II, TATA box

binding protein (TBP)-associated factor,

TAF12 20kDa 1.203286 0.02106946 cytochrome P450, family 24, subfamily A,

CYP24A1 polypeptide 1 1.202964 0.01758295

GNRH2 gonadotropin-releasing hormone 2 1.202871 0.00455354 transient receptor potential cation channel,

TRPC4AP subfamily C, member 4 associated protein 1.202778 0.0247338

Protein phosphatase 2 (formerly 2A),

PPP2R3B regulatory subunit B", beta 1.20235 0.0467168

Similar to ubiquitin-conjugating enzyme E2Q

FLJ43276 2 1.202268 0.03190402

DB1/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

BTNL3 butyrophilin-like 3 1.202192 0.00231857

RGSL1 regulator of G-protein signaling like 1 1.202077 0.00594699

TPO thyroid peroxidase 1.202069 0.01017159

SCEL sciellin 1.201887 0.00233167

SYNJ2 synaptojanin 2 1.201541 0.01137583

EHD1 EH-domain containing 1 1.201044 0.02330411

ACINI apoptotic chromatin condensation inducer 1 1.201026 0.02887224

IL20 interleukin 20 1.20095 0.03008605 family with sequence similarity 90, member

FAM90A1 Al 1.200927 0.00186085

ROD1 regulator of differentiation 1 (S.

ROD1 pombe) 1.200754 0.0474292

UDP-GlcNAc:betaGal beta-l,3-N-

B3GNT5 acetylglucosaminyltransferase 5 1.200695 0.01960692 cAMP responsive element binding protein 3-

CREB3L1 like 1 1.200668 0.01419674

SPON1 spondin 1 , extracellular matrix protein 1.200668 0.02924293

DEPDC5 DEP domain containing 5 1.200388 0.04198871 solute carrier family 4, sodium bicarbonate

SLC4A7 cotransporter, member 7 1.200374 0.01216306

Excision repair cross-complementing rodent

ERCC8 repair deficiency, complementation group 8 1.200211 0.01619386

SARI A SARI homolog A (S. cerevisiae) 1.200178 0.02654978

CCHCR1 coiled-coil alpha-helical rod protein 1 1.200107 0.00917738 acyl-CoA dehydrogenase, short/branched

ACADSB chain 1.20001 0.02790511

MEIS2 Meis homeobox 2 1.199965 0.02108226

DBF4B DBF4 homolog B (S. cerevisiae) 1.199619 0.03549086 interleukin 2 receptor, gamma (severe

IL2RG combined immunodeficiency) 1.199506 0.00788149

CRAMP 1L Crm, cramped-like (Drosophila) 1.199274 0.03778153

CAPN12 Calpain 12 1.199157 0.00757691

KIAA0141 KIAA0141 1.198884 0.03352701 triggering receptor expressed on myeloid

TREML1 cells-like 1 1.198054 0.04780684

NINL ninein-like 1.197949 0.02748427

SLC46A2 solute carrier family 46, member 2 1.197672 0.02290017

ALB albumin 1.197399 0.0411184 transition protein 2 (during histone to

TNP2 protamine replacement) 1.19722 0.00193066

RNA binding motif, single stranded

RBMS3 interacting protein 3 1.196392 0.03757412

EFCAB5 EF-hand calcium binding domain 5 1.196327 0.00695507

RPH3A rabphilin 3 A homolog (mouse) 1.196274 0.03001022

3 -Mar N/A 1.196125 0.01527518

ZNF227 zinc finger protein 227 1.19555 0.01396527

Solute carrier family 22 (organic anion/cation

SLC22A10 transporter), member 10 1.195396 0.04256239

TUBGCP5 tubulin, gamma complex associated protein 5 1.195396 0.02824091

KIAA0317 KIAA0317 1.195135 0.04304959

DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells Gene Symbol Gene Description Fold Ttest P

value

SIK1 salt-inducible kinase 1 1.195008 0.0327209

DnaJ (Hsp40) homolog, subfamily B, member

DNAJB5 5 1.194948 0.02080713

WDR59 WD repeat domain 59 1.194575 0.02706941

WDR90 WD repeat domain 90 1.194397 0.00265406

MOXD1 monooxygenase, DBH-like 1 1.194103 0.02778465

STAB1 stabilin 1 1.193369 0.03979409

MTMR6 myotubularin related protein 6 1.193367 0.03304742 differentially expressed in FDCP 8 homolog

DEF8 (mouse) 1.193266 0.0366666

KRT3 keratin 3 1.19301 0.00261699

C17orf47 chromosome 17 open reading frame 47 1.192946 0.01988324

F13B coagulation factor XIII, B polypeptide 1.192215 0.03738782 protein phosphatase 1, regulatory (inhibitor)

PPP1R3A subunit 3A 1.191818 0.04093887

CLIC5 chloride intracellular channel 5 1.191528 0.02173546

ZDHHC8 zinc finger, DHHC-type containing 8 1.191091 0.018042

DCL 1 doublecortin-like kinase 1 1.190858 0.01408673

CLCN4 chloride channel 4 1.190833 0.03606835

SPATS 1 spermatogenesis associated, serine-rich 1 1.189964 0.02817104

FRMD5 FERM domain containing 5 1.18974 0.02059221 eukaryotic translation initiation factor 3,

EIF3C subunit C 1.18965 0.03850882

C7orf27 chromosome 7 open reading frame 27 1.189607 0.04936258 family with sequence similarity 178, member

FAM178A A 1.189489 0.03542246

UDP glucuronosyltransferase 2 family,

UGT2B4 polypeptide B4 1.18914 0.02762916

C22orf31 chromosome 22 open reading frame 31 1.188471 0.04342905

CFHR3 complement factor H-related 3 1.188091 0.01982027 protein phosphatase 2, regulatory subunit B,

PPP2R2B beta 1.188035 0.02405195

ITPK1 inositol 1,3,4-triphospliate 5/6 kinase 1.187707 0.02648192 wingless-type MMTV integration site family,

W T5A member 5 A 1.187286 0.03638738

GSX2 GS homeobox 2 1.187258 0.04749432

FLJ44048 FLJ44048 protein 1.187132 0.02872413

CAPRIN2 caprin family member 2 1.187106 0.0381396 potassium voltage-gated channel, subfamily H

KCNH6 (eag-related), member 6 1.186893 0.00325637

IMP (inosine 5 '-monophosphate)

IMPDH2 dehydrogenase 2 1.186305 0.02984448

FGG fibrinogen gamma chain 1.18591 0.03549757 solute carrier family 27 (fatty acid

SLC27A3 transporter), member 3 1.185586 0.02812566

TEX11 testis expressed 11 1.18556 0.02007695 patatin-like phospholipase domain containing

PNPLA1 1 1.185535 0.02326484

CDP-diacylglycerol synthase (phosphatidate

C cytidylyltransferase) 1

nR1 /DfiQS/m1₅16 i 1.184946 0.02636899 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

Solute carrier family 27 (fatty acid

SLC27A6 transporter), member 6 0.03970073

DPYSL2 dihydropyrimidinase-like 2 0.02182736

MCTP1 multiple C2 domains, transmembrane 1 0.03360385

TRIB1 tribbles homolog 1 (Drosophila) 0.02736849

IFI16 interferon, gamma-inducible protein 16 0.0074908

CDH3 cadherin 3, type 1, P-cadherin (placental) 0.01625922

DnaJ (Hsp40) homolog, subfamily C, member

DNAJC16 16 0.0261288

DGKG diacylglycerol kinase, gamma 90kDa 0.039706

BPY2 basic charge, Y-linked, 2 0.03254044

ZNF583 zinc finger protein 583 0.02485305

ADAM30 ADAM metallopeptidase domain 30 0.00616206

DTNA dystrobrevin, alpha 0.02930348

CASR calcium-sensing receptor 0.03323074

ZNF345 zinc finger protein 345 0.00924459

ZNF509 Zinc finger protein 509 0.04998016

ZNRF1 zinc and ring finger 1 0.0099705

DPY19L3 dpy-19-like 3 (C. elegans) 0.01666136

ATP13A1 ATPase type 13 Al 0.04005452

W K4 WNK lysine deficient protein kinase 4 0.04657409

NPSR1 neuropeptide S receptor 1 0.02172977

ZNF687 zinc finger protein 687 0.02918329 alanyl-tRNA synthetase 2, mitochondrial

AARS2 (putative) 1.180396 0.02086541

Golgi autoantigen, golgin subfamily a-like

FLJ401 13 pseudogene 1.180388 0.00047194 adaptor-related protein complex 4, beta 1

AP4B1 subunit 0.01384674

KPNA5 karyopherin alpha 5 (importin alpha 6) 0.02793043

IMPG1 interphotoreceptor matrix proteoglycan 1 0.03330314

COL9A1 collagen, type IX, alpha 1 0.02346278

WDR46 WD repeat domain 46 0.01295145

HYI hydroxypyruvate isomerase homolog (E. coli) 0.03586758

Golgi associated, gamma adaptin ear

GGA1 containing, ARF binding protein 1 0.01209954

MAB21L2 mab-21-like 2 (C. elegans) 0.01490822

PDZD2 PDZ domain containing 2 0.04742919

KIAA0467 KIAA0467 0.00480777

MY09B myosin IXB 0.00019001

PAX3 paired box 3 0.02956595

NIDI nidogen 1 0.02300942

ALOXE3 Arachidonate lipoxygenase 3 0.04581467

1 -acylglycerol-3 -phosphate O-acyltransf erase

4 (lysophosphatidic acid acyltransferase,

AGPAT4 delta) 0.00637736

RNF25 Ring finger protein 25 0.02427105

FOXP2 forkhead box P2 0.02296124

PNMAL1 PNMA-like 1 0.04671811

TRPV6 transient receptor potential cation channel, 0.00208195

DBl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value subfamily V, member 6

ZNF607 zinc finger protein 607 1.17363 0.01986909

DSC3 desmocollin 3 1.173507 0.00852276

Histidine acid phosphatase domain containing

HISPPD2A 2A 1.173422 0.04406193

AHNAK AHNAK nucleoprotein 1.173278 0.0004565 pleckstrin homology domain containing,

PLEKH02 family O member 2 1.17267 0.01898245

PLCB4 phospholipase C, beta 4 1.172513 0.04330856

C16orf68 chromosome 16 open reading frame 68 1.17127 0.01823989 signal transducer and activator of

STAT5A transcription 5A 1.170663 0.01131636

CLEC18A C-type lectin domain family 18, member A 1.17033 0.0455398 intraflagellar transport 52 homolog

IFT52 (Chlamydomonas) 1.16959 0.01712765

NOL6 nucleolar protein family 6 (RNA-associated) 1.169534 0.04780299

LON peptidase N-terminal domain and ring

LONRF1 finger 1 1.169296 0.03987327

C6orf58 chromosome 6 open reading frame 58 1.168817 0.03032013

NPHP4 nephronophthisis 4 1.168254 0.03145141

GNPAT glyceronephosphate O-acyltransferase 1.167893 0.02519736

KIAA0355 KIAA0355 1.167416 0.01082776

PABPC3 poly(A) binding protein, cytoplasmic 3 1.167305 0.02673658

SPACA3 Sperm acrosome associated 3 1.16728 0.0489063

C20orfl l7 chromosome 20 open reading frame 117 1.167178 0.04091815

PRR18 proline rich 18 1.167034 0.01554887

SEC23A Sec23 homolog A (S. cerevisiae) 1.166758 0.0064721

ZNF783 zinc finger family member 783 1.166506 0.01530829 epidermal growth factor receptor

(erythroblastic leukemia viral (v-erb-b)

EGFR oncogene homolog, avian) 1.166192 0.04292096

THAP9 THAP domain containing 9 1.166034 0.02042772 folliculogenesis specific basic helix-loop-

FIGLA helix 1.165536 0.04868311

KLHDC9 kelch domain containing 9 1.165134 0.0305178

PIWIL2 piwi-like 2 (Drosophila) 1.164572 0.02796603 cleavage and polyadenylation specific factor

CPSF7 7, 59kDa 1.164181 0.04438468

HSH2D hematopoietic SH2 domain containing 1.163909 0.02101095

MAN2B1 mannosidase, alpha, class 2B, member 1 1.163671 0.0230003

TMEM40 transmembrane protein 40 1.163525 0.01127356

Adhesion molecule, interacts with CXADR

AMICA1 antigen 1 1.162197 0.03518972

NAT 11 N-acetyltransferase 11 1.161757 0.00136992

NOSTRIN nitric oxide synthase trafficker 1.161744 0.04875515

WDR77 WD repeat domain 77 1.161034 0.0464362

SEZ6 Seizure related 6 homolog (mouse) 1.160645 0.00582668

HSFY2 heat shock transcription factor, Y linked 2 1.160551 0.04492153

GMPS guanine monphosphate synthetase 1.160098 0.02920418

PDCD1 1 programmed cell death 11 1.159681 0.03268893

Bl/ 69437516.1 Supplemental Table 1. Gene Transcripts Upregulated by Lactate in MCF7 Cells

Gene Symbol Gene Description Fold Ttest P

Change value

KIF27 kinesin family member 27 1.159524 0.00724317 fms-related tyrosine kinase 1 (vascular

endothelial growth factor/vascular

FLT1 permeability factor receptor) 1.158691 0.02251696

ESR1 estrogen receptor 1 1.158432 0.04355614

IP013 importin 13 1.158266 0.04110354

CD1D CD Id molecule 1.157526 0.0488465

C16orf58 chromosome 16 open reading frame 58 1.157353 0.01567337

RXFP2 relaxin/insulin-like family peptide receptor 2 1.157118 0.03208373

POTEG POTE ankyrin domain family, member G 1.15675 0.0279091

ZW10, kinetochore associated, homolog

ZW10 (Drosophila) 1.156689 0.04370405

HFM1, ATP-dependent DNA helicase

HFM1 homolog (S. cerevisiae) 1.155649 0.01725609

ZNF620 zinc finger protein 620 1.155478 0.01498643

EFCAB7 EF-hand calcium binding domain 7 1.155364 0.04868796 neighbor of BRCA1 gene 2 (non-protein

NBR2 coding) 1.154574 0.0342684 translocase of inner mitochondrial membrane

TIMM8A 8 homolog A (yeast) 1.154276 0.01892605

GOSR2 golgi SNAP receptor complex member 2 1.154174 0.02083885

HVCN1 hydrogen voltage-gated channel 1 1.153664 0.04150092 integrin, alpha L (antigen CD11A (pi 80),

lymphocyte function-associated antigen 1 ;

ITGAL alpha polypeptide) 1.153175 0.0121027

TCP10L T-complex 10 (mouse)-like 1.153159 0.02041266

CILP2 cartilage intermediate layer protein 2 1.153042 0.0248711 1

HIST1H4F histone cluster 1 , H4f 1.152071 0.0381848

SORBS3 sorbin and SH3 domain containing 3 1.151912 0.0398458

IL22RA1 interleukin 22 receptor, alpha 1 1.151869 0.03723606

PPP4R1 protein phosphatase 4, regulatory subunit 1 1.151406 0.0099078

C3orf35 chromosome 3 open reading frame 3 1.151345 0.01326453 cytochrome P450, family 2, subfamily C,

CYP2C18 polypeptide 18 1.151319 0.04873183 FLJ25715 hypothetical protein FLJ25715 1.150845 0.03539013 DGKB diacylglycerol kinase, beta 90kDa 1.150602 0.02125358 AKAP2 A kinase (PRKA) anchor protein 2 1.150537 0.02056527 intraflagellar transport 172 homolog

IFT172 (Chlamydomonas) 1.150365 0.02101366

Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P

Symbol Change value

CECR6 cat eye syndrome chromosome region, candidate 6 4.533043 0.00120481 THOC5 THO complex 5 4.256919 0.00876836 APPL2 adaptor protein, phosphotyrosine interaction, PH 3.836681 0.04778387 domain and leucine zipper containing 2

PSMG2 proteasome (prosome, macropain) assembly 3.493733 0.03165942

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P

Symbol Change value

chaperone 2

Clorfl07 chromosome 1 open reading frame 107 3.395923 0.00436079

CHMP7 CHMP family, member 7 3.295925 0.04618667

DOCK1 dedicator of cytokinesis 1 3.213632 0.03198286

MDN1 MDNl. midasin homolog (yeast) 3.211667 0.02237256

RBM43 #N/A 3.196485 0.00631414

CCNT1 cyclin Tl 3.106008 0.0342957

IFT52 intraflagellar transport 52 homolog 3.046151 0.01229609

(Chi amydomonas)

ABCA12 ATP-binding cassette, sub-family A (ABC1), 3.02442 0.00623101 member 12

FBX025 F-box protein 25 3.021057 0.00368625

G3BP1 GTPase activating protein (SH3 domain) binding 2.994202 0.01682477 protein 1

ITPR1 inositol 1,4, -triphosphate receptor, type 1 2.988401 0.00625779

MED1 mediator complex subunit 1 2.96932 0.0409564

Clorf54 #N/A 2.955018 0.00026548

ELK1 ELK1, member ofETS oncogene family 2.954365 0.01660971

NUP214 nucleoporin 214kDa 2.948931 0.0326838

INADL InaD-like (Drosophila) 2.899368 0.00507621

HCN4 hyperpolarization activated cyclic nucleotide-gated 2.889932 0.02627041 potassium channel 4

ALKBH5 alkB, alkylation repair homolog 5 (E. coli) 2.85896 0.03354708

DOLK dolichol kinase 2.854543 0.01302542

ATP8B2 ATPase, class I, type 8B, member 2 2.850312 0.04602733

ERRFIl ERBB receptor feedback inhibitor 1 2.848611 0.03785734

CTNNBL catenin, beta like 1 2.847563 0.04508615 1

STIM2 stromal interaction molecule 2 2.835404 0.0459367

TNK2 tyrosine kinase, non-receptor, 2 2.830558 0.03729109

BAX BCL2-associated X protein 2.80332 0.04525024

PI4K2A #N/A 2.796562 0.0050034

FUNDC2 FUN14 domain containing 2 2.773584 0.00524994

MAP3K2 mitogen-activated protein kinase kinase kinase 2 2.768704 0.04766367

N T nicotinamide nucleotide transhydrogenase 2.768045 0.00941208

RAB30 RAB30, member RAS oncogene family 2.747985 0.04482544

CTSA cathepsin A 2.746964 0.03877969

AFF1 AF4/FMR2 family, member 1 2.739383 0.04907813

DDHD2 DDHD domain containing 2 2.735836 0.04539782

NUDT9 nudix (nucleoside diphosphate linked moiety X)- 2.735101 0.00850058 type motif 9

BRAF v-raf murine sarcoma viral oncogene homolog B 1 2.734356 0.03364438

THBS3 thrombospondin 3 2.718379 0.02243978

DHX57 DEAH (Asp-Glu-Ala-Asp/His) box polypeptide 2.71681 0.01686649

57

C6orfl68 chromosome 6 open reading frame 168 2.709293 0.02722808

R3HDM2 R3H domain containing 2 2.709092 0.00453719

SMURF1 SMAD specific E3 ubiquitin protein ligase 1 2.701271 0.01558087

UTRN utrophin 2.695947 0.01243512

BRD8 bromodomain containing 8 2.694947 0.00909826 1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

IL1RAP interleukin 1 receptor accessory protein 2.694309 0.02831857

NBEA neurobeachin 2.693884 0.02193306

DIAPH1 diaphanous homolog 1 (Drosophila) 2.685718 0.03000495

MKRN1 makorin ring finger protein 1 2.685032 0.00157199

SYT10 Synaptotagmin X 2.65176 0.01295566

DENND5 DENN/MADD domain containing 5 A 2.651474 0.00964955

A

CCNA1 cyclin Al 2.633936 0.01471915 L CH1 leucine-rich repeats and calponin homology (CH) 2.632229 0.00031883 domain containing 1

DUSP8 dual specificity phosphatase 8 2.6292 0.01137426 TIA 1 T-cell lymphoma invasion and metastasis 1 2.626128 0.03662284

CLPTM1 CLPTMl-like 2.601228 0.03868694 L

STIL SCL/TAL1 interrupting locus 2.59729 0.0397914

TNP03 transportin 3 2.593873 0.00926626

SYMPK symplekin 2.587307 0.03074672

CCNT2 cyclin T2 2.569067 0.04655543

NRP1 neuropilin 1 2.560962 0.02981305

SHQ1 SHQ1 homolog (S. cerevisiae) 2.555645 0.02299193

MAP7D1 MAP7 domain containing 1 2.54933 0.01099938

TECPR2 tectonin beta-propeller repeat containing 2 2.542771 0.04968312

MED23 mediator complex subunit 23 2.540537 0.04879873

ATXN10 ataxin 10 2.539384 0.03524992

DGKA diacylglycerol kinase, alpha 80kDa 2.529001 0.0313754

KIAA024 KIAA0247 2.523791 0.00087761

7

SNAP29 synaptosomal-associated protein, 29kDa 2.51839 0.04622785

RAB31 RAB31 , member RAS oncogene family 2.516195 0.01067045

SSH3 slingshot homolog 3 (Drosophila) 2.50875 0.04233709

C12orf41 chromosome 12 open reading frame 41 2.503165 0.03954708

TTLL1 #N/A 2.496067 0.01179622

HIP 2 Homeodomain interacting protein kinase 2 2.494198 0.01556645

DDOST dolichyl-diphosphooligosaccharide—protein 2.491522 0.04739844 glycosyltransferase

PRPF38A PRP38 pre-mRNA processing factor 38 (yeast) 2.486744 0.03023817 domain containing A

PFKM phosphofructokinase, muscle 2.486039 0.01023407

SEC23B Sec23 homolog B (S. cerevisiae) 2.485522 0.01805283

ABHD11 abhydrolase domain containing 11 2.485291 0.0361806

CCNL2 cyclin L2 2.48232 0.03744227

MTRR 5-methyltetrahydrofolate-homocysteine 2.481257 0.02012838 methyltransferase reductase

NRCAM neuronal cell adhesion molecule 2.480739 0.04752255 UBR4 ubiquitin protein ligase E3 component n-recognin 2.479947 0.01080766

4

CDC42BP CDC42 binding protein kinase beta (DMPK-like) 2.475429 0.03133293 B

DPP3 dipeptidyl-peptidase 3 2.475017 0.03076931 FN1 fibronectin 1 2.470361 0.04517357 1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value

MTERFD MTERF domain containing 2 2.468774 0.0476033 2

MRPL20 Mitochondrial ribosomal protein L20 2.457955 0.03422195

TD D5 tudor domain containing 5 2.453438 0.02693238 TUB A3 E #N/A 2.448859 0.03693353

WWP2 WW domain containing E3 ubiquitin protein 2.447361 0.01863292 ligase 2

CDC 16 #N/A 2.444693 0.04661557 SLC28A2 #N/A 2.443784 0.00364928

Magmas Mitochondria-associated protein involved in 2.443612 0.01427752 granulocyte-macrophage colony-stimulating factor

signal transduction

CDKL5 cyclin-dependent kinase-like 5 2.442396 0.03637012

PCSK7 proprotein convertase subtilisin/kexin type 7 2.441475 0.00070709

KCTD7 potassium channel tetramerisation domain 2.439878 0.0215569 containing 7

FAM129B family with sequence similarity 129, member B 2.436956 0.02104844

IFITM3 #N/A 2.435717 0.04163527

BAI2 brain-specific angiogenesis inhibitor 2 2.42976 0.00770509

MCRS1 microspherule protein 1 2.42666 0.04946973

LAD1 ladinin 1 2.425137 0.03088459

EDF1 #N/A 2.424154 0.04204104

KLHL 12 kelch-like 12 (Drosophila) 2.414911 0.01191345

NUBPL nucleotide binding protein-like 2.410654 0.01757646

LCN10 #N/A 2.410291 0.00584889

ULBP2 #N/A 2.405626 0.02840472

HMCN1 hemicentin 1 2.404099 0.00163052

CD44 CD44 molecule (Indian blood group) 2.403065 0.0344324

INVS inversin 2.402863 0.01659962

ITGB6 integrin, beta 6 2.391807 0.02136789

RFX3 #N/A 2.390793 0.01644792

MCF2L #N/A 2.388832 0.00513299

NICNl nicolin 1 2.388529 0.00908688

PCGF1 poly comb group ring finger 1 2.386976 0.03418426

TNPOl transportin 1 2.3849 0.03820035

TECPR1 tectonin beta-propeller repeat containing 1 2.383271 0.04004739 FEZ1 #N/A 2.382444 0.01408375

YY1AP1 YY1 associated protein 1 2.382036 0.0456202

CPE carboxypeptidase E 2.379491 0.02678441

EHMT1 euchromatic histone-lysine N-methyltransferase 1 2.378332 0.00038361

NDUFAF NADH dehydrogenase (ubiquinone) 1 alpha 2.378237 0.00163131

1 subcomplex, assembly factor 1

MLH3 mutL homolog 3 (E. coli) 2.376897 0.00584984 CKAP2L cytoskeleton associated protein 2-like 2.375931 0.04127031 PYROXD pyridine nucleotide-disulphide oxidoreductase 2.370243 0.04256643

2 domain 2

WDFY2 WD repeat and FYVE domain containing 2 2.369515 0.01867335

NANOS1 nanos homolog 1 (Drosophila) 2.369388 0.02870312

SUMF2 sulfatase modifying factor 2 2.365256 0.04452999

MYST2 MYST histone acetyltransferase 2 2.363382 0.0251515 1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

ZNF287 zinc finger protein 287 2.355907 0.04074512 CDS2 CDP-diacylglycerol synthase (phosphatidate 2.352796 0.04019579 cytidylyltransferase) 2

EPHX1 epoxide hydrolase 1, microsomal (xenobiotic) 2.352754 0.01354618

SNAPIN SNAP-associated protein 2.35105 0.04268937

THAP1 1 THAP domain containing 1 1 2.350904 0.02869954

HSD17B7 Hydroxysteroid (17-beta) dehydrogenase 7 2.346188 0.02274892

P2 pseudogene 2

TNIP2 TNFAIP3 interacting protein 2 2.342348 0.03096003

SFX 1 sideroflexin 1 2.34231 0.04322009

RNFT2 ring finger protein, transmembrane 2 2.341714 0.02755541

SOLH small optic lobes homolog (Drosophila) 2.33619 0.04058995

LRBA LPS-responsive vesicle trafficking, beach and 2.334046 0.03741658 anchor containing

ANK D1 ankyrin repeat domain 1 1 2.332943 0.01490882 1

SPDYE8P speedy homolog E8 (Xenopus laevis), pseudogene 2.327864 0.04429203

PHC3 polyhomeotic homolog 3 (Drosophila) 2.327043 0.04774561

PPP5C protein phosphatase 5, catalytic subunit 2.32173 0.04246803

DFNB31 Deafness, autosomal recessive 31 2.321165 0.00480601

SLC25A3 solute carrier family 25, member 35 2.319554 0.01088912

5

HISPPD2 Histidine acid phosphatase domain containing 2A 2.316541 0.03473277 A

SLC25A4 #N/A 2.315244 0.0324995 3

LYG2 lysozyme G-like 2 2.313446 0.03256065 SUSD2 sushi domain containing 2 2.308653 0.00076784 TTC4 tetratricopeptide repeat domain 4 2.305393 0.01134933 PIP5K1A phosphatidylinositol-4-phosphate 5-kinase, type I, 2.30314 0.00122676 alpha

MZF1 myeloid zinc finger 1 2.300058 0.0424067

TNNT3 troponin T type 3 (skeletal, fast) 2.299284 0.00978502

ELOVL6 ELOVL family member 6, elongation of long 2.298864 0.02905437 chain fatty acids (FENl/Elo2, SUR4/Elo3-like,

yeast)

KIAA009 KIAA0090 2.294906 0.00981731 0

BFAR bifunctional apoptosis regulator 2.293413 0.00416696 IFT122 intraflagellar transport 122 homolog 2.286489 0.04948514

(Chlamydomonas)

CDCA7L cell division cycle associated 7-like 2.28315 0.00620642

A APC1 anaphase promoting complex subunit 1 2.282745 0.0410648

C5orf25 chromosome 5 open reading frame 25 2.282417 0.04256676

AP3M2 #N/A 2.281407 0.02326857

R F115 ring finger protein 1 15 2.28131 0.04092934

OSBPL1A oxysterol binding protein-like 1A 2.28078 0.03304009

SMARCB SWI/SNF related, matrix associated, actin 2.279405 0.0346208

1 dependent regulator of chromatin, subfamily b,

member 1

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

FAM53C family with sequence similarity 53, member C 2.279002 0.02147619 SLC4A7 solute carrier family 4, sodium bicarbonate 2.276701 0.00738148 cotransporter, member 7

CYB5R3 cytochrome b5 reductase 3 2.273478 0.00146646 ΗΓΝΤ2 histidine triad nucleotide binding protein 2 2.272342 0.02016666 CTNNB 1 catenin (cadherin-associated protein), beta 1 , 2.268497 0.00091218

88kDa

LRP IB low density lipoprotein receptor-related protein 1 B 2.268244 0.01037608

SYTL2 Synaptotagmin-like 2 2.266834 0.04720219

Clorf55 chromosome 1 open reading frame 55 2.266459 0.02062753

DOT1L DOTl-like, histone H3 methyltransferase (S. 2.266164 0.04398079 cerevisiae)

PRUNE prune homolog (Drosophila) 2.261951 0.04105039 TCP1 1L2 t-complex 11 (mouse)-like 2 2.260427 0.03597573 ABCG2 ATP-binding cassette, sub-family G (WHITE), 2.258303 0.02678408 member 2

NDUFA1 NADH dehydrogenase (ubiquinone) 1 alpha 2.255936 0.0162317 3 subcomplex, 13

EIF2B5 eukaryotic translation initiation factor 2B, subunit 2.254942 0.04669815

5 epsilon, 82kDa

TCP11L1 #N/A 2.252361 0.02498018 TULP3 tubby like protein 3 2.252197 0.03918548

PLCG2 phospholipase C, gamma 2 (phosphatidylinositol- 2.251615 0.03035352 specific)

CLEC2D C-type lectin domain family 2, member D 2.250092 0.03239425

MAPKAP #N/A 2.247765 0.01969152

K5

DCTN1 dynactin 1 (pi 50, glued homolog, Drosophila) 2.247297 0.0361356 NF1 neurofibromin 1 2.246597 0.04162672

SIPA1L2 signal-induced proliferation-associated 1 like 2 2.244631 0.03842635

C9orf97 Chromosome 9 open reading frame 97 2.244268 0.00859059

CTSH #N/A 2.244056 0.03205423

CDKN 1 A cyclin-dependent kinase inhibitor 1 A (p21 , Cip 1 ) 2.238879 0.01566499

SYNJ2 synaptojanin 2 2.238072 0.02730281

NCOA1 nuclear receptor coactivator 1 2.235876 0.0373691

SLC37A3 solute carrier family 37 (glycerol-3 -phosphate 2.235513 0.04866478 transporter), member 3

MGAT4B mannosyl (alpha-l,3-)-glycoprotein beta-l,4-N- 2.233658 0.04886326 acetylglucosaminyltransferase, isozyme B

ABLIM3 actin binding LIM protein family, member 3 2.231371 0.0235566 MAP 1 B microtubule-associated protein 1 B 2.227853 0.00050307 GPR87 G protein-coupled receptor 87 2.225246 0.04203909 SGSM2 small G protein signaling modulator 2 2.223093 0.01792753 HSDL2 hydroxysteroid dehydrogenase like 2 2.220989 0.04626046 WARS2 tryptophanyl tRNA synthetase 2, mitochondrial 2.216981 0.00420204 PIGA #N/A 2.215978 0.02372293 HAGHL Hydroxyacylglutathione hydrolase-like 2.210443 0.04351155 ARAP2 ArfGAP with RhoGAP domain, ankyrin repeat 2.210235 0.03732842 and PH domain 2

OP A3 Optic atrophy 3 (autosomal recessive, with chorea 2.209787 0.00171029

DBl/ 6943751₆.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

and spastic paraplegia)

CHRM3 #N/A 2.209625 0.02107095

C3orf23 chromosome 3 open reading frame 23 2.209375 0.01667732

PHF8 PHD finger protein 8 2.206374 0.0307203

TMEM18 transmembrane protein 189 2.206157 0.02937023

9

ZFYVE27 #N/A 2.205437 0.0258554 DENND2 DEN /MADD domain containing 2C 2.203543 0.04263647 C

STRADA STE20-related kinase adaptor alpha 2.203056 0.02903358

TCTN1 tectonic family member 1 2.200135 0.02398527

MUT methylmalonyl CoA mutase 2.19871 1 0.04875338

RICS Rho GTPase-activating protein 2.198536 0.03531902

SEC14L2 SEC14-like 2 (S. cerevisiae) 2.197791 0.02157167

GIMAP6 GTPase, IMAP family member 6 2.197772 0.01959113

BCORL1 BCL6 co-repressor-like 1 2.19311 1 0.02543076

C19orf62 chromosome 19 open reading frame 62 2.191676 0.03154505

FIG4 FIG4 homolog, SAC1 lipid phosphatase domain 2.191472 0.01514057 containing (S. cerevisiae)

FBXL13 F-box and leucine-rich repeat protein 13 2.18993 0.02806166

ECE1 endothelin converting enzyme 1 2.189231 0.01296876

NT5DC2 5 '-nucleotidase domain containing 2 2.188765 0.028676

CNOT6L CCR4-NOT transcription complex, subunit 6-like 2.188121 0.00901903

TCEA2 transcription elongation factor A (SII), 2 2.187952 0.04357233

ERLIN2 ER lipid raft associated 2 2.184886 0.01319339

ITIH5L inter-alpha (globulin) inhibitor H5-like 2.183908 0.04573874

ZNF384 zinc finger protein 384 2.181926 0.0096138

ADCY1 adenylate cyclase 1 (brain) 2.180825 0.04306117

MSI1 #N/A 2.180303 0.01207864

WDR22 WD repeat domain 22 2.180082 0.02028217

FBXL3 F-box and leucine-rich repeat protein 3 2.176911 0.01974647

NPR1 natriuretic peptide receptor A/guanylate cyclase A 2.176805 0.02348208

(atrionatriuretic peptide receptor A)

NBAS neuroblastoma amplified sequence 2.176022 0.03688986 ERCC3 excision repair cross-complementing rodent repair 2.175934 0.00899813 deficiency, complementation group 3 (xeroderma

pigmentosum group B complementing)

C6orfl06 chromosome 6 open reading frame 106 2.174662 0.01419501 CACNA1 calcium channel, voltage-dependent, L type, alpha 2.170782 0.00748575 D ID subunit

C7orf41 chromosome 7 open reading frame 41 2.170586 0.04491985

DENND4 DENN/MADD domain containing 4C 2.170566 0.01230614

C

MYCBP2 MYC binding protein 2 2.168534 0.02526474 KIAA056 KIAA0562 2.167178 0.01401037 2

EFTUD1 elongation factor Tu GTP binding domain 2.166378 0.01642407 containing 1

SP140 SP140 nuclear body protein 2.164286 0.04002558 MRPL19 mitochondrial ribosomal protein LI 9 2.163857 0.02878438

DB1/ 69₄37516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

IRF7 interferon regulatory factor 7 2.163552 0.01010416

SCFD2 seel family domain containing 2 2.163273 0.04389159

GDAP1L1 Ganglioside-induced differentiation-associated 2.162375 0.03060397 protein 1 -like 1

TMEM67 transmembrane protein 67 2.161969 0.02357079 PSME3 proteasome (prosome, macropain) activator 2.161553 0.03295222 subunit 3 (PA28 gamma; Ki)

KIF1B kinesin family member 1 B 2.160942 0.02563078

RUVBL1 RuvB-like 1 (E. coli) 2.159586 0.03309362

PTGR1 prostaglandin reductase 1 2.158659 0.00752827

COG5 component of oligomeric golgi complex 5 2.157755 0.0404852

RPAP1 RNA polymerase II associated protein 1 2.156564 0.01591496

TMEM18 transmembrane protein 184A 2.155301 0.02641933

4A

Clorfl57 #N/A 2.15439 0.03582529 PSMA2 proteasome (prosome, macropain) subunit, alpha 2.153033 0.01873174 type, 2

FNBP1 formin binding protein 1 2.152364 0.02691663

PAK3 p21 protein (Cdc42/Rac)-activated kinase 3 2.151948 0.01846905

CHST10 carbohydrate sulfotransferase 10 2.151551 0.02781973

HIST1H2 #N/A 2.151105 0.03021859

AI

TP53BP2 tumor protein p53 binding protein, 2 2.150413 0.0349378

PEX11A peroxisomal biogenesis factor 11 alpha 2.150314 0.03310421

CLTCL1 clathrin, heavy chain-like 1 2.149373 0.03834021

MAP3 5 mitogen-activated protein kinase kinase kinase 5 2.14786 0.00358042

TBC1D5 TBC1 domain family, member 5 2.146839 0.00272191

LRRC16A leucine rich repeat containing 16A 2.14675 0.02601013

ZNF318 zinc finger protein 318 2.146698 0.04063381

CNTFR ciliary neurotrophic factor receptor 2.146664 0.03768583

ARHGEF Rho guanine nucleotide exchange factor (GEF) 12 2.145732 0.00866423

12

CALCA #N/A 2.145508 0.03035912

DOCK7 dedicator of cytokinesis 7 2.144975 0.01593592

CCT3 chaperonin containing TCP1, subunit 3 (gamma) 2.143663 0.03791006

FANCI Fanconi anemia, complementation group I 2.143024 0.03029496

ST3GAL5 ST3 beta-galactoside alpha-2,3-sialyltransferase 5 2.141182 0.00246875

BCL2L14 BCL2-like 14 (apoptosis facilitator) 2.140794 0.04084361

PRKCI protein kinase C, iota 2.14033 0.01913295

LIG3 ligase III, DNA, ATP-dependent 2.139885 0.00637983

KRT16 keratin 16 2.136947 0.0357481

STARD5 StAR-related lipid transfer (START) domain 2.135108 0.01409282 containing 5

TPD52 tumor protein D52 2.134887 0.03438915

TNS1 tensin 1 2.133585 0.02192764

NACAP1 nascent-polypeptide-associated complex alpha 2.13347 0.04814159 polypeptide pseudogene 1

ANTXR1 anthrax toxin receptor 1 2.131767 0.03135031 KCNK18 #N/A 2.131568 0.03880469 NIACRl #N/A 2.130256 0.01031739

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P

Symbol Change value

CHD1L chromodomain helicase DNA binding protein 1- 2.12969 0.00196612 like

PHLDB2 pleckstrin homology-like domain, family B, 2.129192 0.0359393 member 2

TGFBI transforming growth factor, beta-induced, 68kDa 2.12691 0.03594676

DDX42 DEAD (Asp-Glu- Ala-Asp) box polypeptide 42 2.125766 0.03480201

TULP4 tubby like protein 4 2.12511 0.00579006

EXOC4 exocyst complex component 4 2.124352 0.03322826

TAF 1 A TATA box binding protein (TBP)-associated 2.123803 0.01221043 factor, RNA polymerase I, A, 48kDa

C3orf34 chromosome 3 open reading frame 34 2.123355 0.0105264 DOCK6 dedicator of cytokinesis 6 2.123338 0.00285469

ETFDH electron-transferring-flavoprotein dehydrogenase 2.122325 0.02860394 KDM5A lysine (K)-specific demethylase 5A 2.121029 0.01623086 T IT1 tR A isopentenyltransferase 1 2.120578 0.02390976 KIR2DS4 #N/A 2.1 1998 0.01305444 LATS2 LATS, large tumor suppressor, homolog 2 2.119657 0.02938295

(Drosophila)

ANKRD2 ankyrin repeat domain 27 (VPS9 domain) 2.11918 0.02611183 7

ANKS 1 A ankyrin repeat and sterile alpha motif domain 2.1 19086 0.04136303 containing 1A

ASXL2 additional sex combs like 2 (Drosophila) 2.116091 0.04307021 MAN2A1 mannosidase, alpha, class 2 A, member 1 2.115693 0.03192584 PE 1 peroxisomal biogenesis factor 1 2.114996 0.00307576

TUB tubby homolog (mouse) 2.114292 0.00094413

MAP3K4 mitogen-activated protein kinase kinase kinase 4 2.1 14067 0.02121523 ZNF235 zinc finger protein 235 2.113243 0.04503107 HARBI1 #N/A 2.113096 0.03103975 POLR3C polymerase (RNA) III (DNA directed) polypeptide 2.11243 0.04340473

C (62kD)

FLOT2 #N/A 2.111448 0.04280161 PARN poly(A)-specific ribonuclease (deadenylation 2.1 11073 0.03680447 nuclease)

TRIP 12 thyroid hormone receptor interactor 12 2.109385 0.0351422

LSG1 large subunit GTPase 1 homolog (S. cerevisiae) 2.107797 0.03808136

LHPP #N/A 2.10708 0.04218035

H2AFY H2A histone family, member Y 2.106526 0.03868839

GLB1 galactosidase, beta 1 2.105544 0.0320468

CNOT4 CCR4-NOT transcription complex, subunit 4 2.103723 0.02611243 SPG20 spastic paraplegia 20 (Troyer syndrome) 2.103392 0.00306415 DAP3 death associated protein 3 2.103304 0.03983598

UBR1 Ubiquitin protein ligase E3 component n-recognin 2.103247 0.04650921

1

MPDU1 mannose-P-dolichol utilization defect 1 2.102917 0.01760447 P4HA2 prolyl 4-hydroxylase, alpha polypeptide II 2.102565 0.03821474 PHF23 #N/A 2.10236 0.00738597 ABCC4 ATP-binding cassette, sub-family C (CFTR/MRP), 2.100129 0.028971 member 4

GM2A GM2 ganglioside activator 2.099143 0.03785905

DB1/ 69437₅16.1 Supplemental Table 2 Gene Transcripts Upreguiated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

ZFYVE26 zinc finger, FYVE domain containing 26

PARP1 poly (ADP-ribose) polymerase 1

DPYSL5 dihydropyrimidinase-like 5

EXOC6 exocyst complex component 6

FAM48A family with sequence similarity 48, member A

RPA2 replication protein A2, 32kDa

ANKH ankylosis, progressive homolog (mouse)

MRPS22 Mitochondrial ribosomal protein S22

SLC5A8 #N/A

SPR sepiapterin reductase (7,8- dihydrobiopterin:NADP+ oxidoreductase)

FBXW11 F-box and WD repeat domain containing 11

PCSK4 Proprotein convertase subtilisin/kexin type 4

SPON1 spondin 1, extracellular matrix protein

HJURP Holliday junction recognition protein

DNAJB6 DnaJ (Hsp40) homolog, subfamily B, member 6

BDH2 3-hydroxybutyrate dehydrogenase, type 2

LTB4R2 leukotriene B4 receptor 2

ZNF638 zinc finger protein 638

THAP1 THAP domain containing, apoptosis associated

protein 1

PRKCD protein kinase C, delta

TMC2 transmembrane channel-like 2

PITPNM1 phosphatidylinositol transfer protein, membrane- associated 1

FAM1 14A family with sequence similarity 114, member Al

1

FIS1 fission 1 (mitochondrial outer membrane)

homolog (S. cerevisiae)

DYM dymeclin

PPARA peroxisome proliferator-activated receptor alpha

HOXB2 #N/A

GGA3 #N/A

FARP1 FERM, RhoGEF (ARHGEF) and pleckstrin

domain protein 1 (chondrocyte-derived)

GNPDA1 glucosamine-6-phosphate deaminase 1

C16orf35 chromosome 16 open reading frame 35

SLC25A3 #N/A

3

ABCC5 ATP-binding cassette, sub-family C (CFTR/MRP),

member 5

MYH11 myosin, heavy chain 11 , smooth muscle

DCLRE1 DNA cross-link repair 1 A (PS02 homolog, S.

A cerevisiae)

C4orf41 chromosome 4 open reading frame 41

MYH9 myosin, heavy chain 9, non-muscle

SNCAIP synuclein, alpha interacting protein

FAM117A family with sequence similarity 117, member A

PRDX3 peroxiredoxin 3

RP9 retinitis pigmentosa 9 (autosomal dominant)

DB l/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P

Symbol Change value

LRP10 low density lipoprotein receptor-related protein 10 2.065981 0.04553922 ERAL1 #N/A 2.065922 0.04248234 GPR125 G protein-coupled receptor 125 2.064453 0.01530749 ZP3 zona pellucida glycoprotein 3 (sperm receptor) 2.064019 0.00642625

TRAF3IP TNF receptor-associated factor 3 interacting 2.063173 0.03736506 1 protein 1

GTPBP1 GTP binding protein 1 2.063154 0.02305996

MACF1 microtubule-actin crosslinking factor 1 2.062381 0.03102047

CLGN calmegin 2.062335 0.00884516

SH2B1 SH2B adaptor protein 1 2.061791 0.00890218

JAG1 Jagged 1 (Alagille syndrome) 2.061732 0.04527461

CAST calpastatin 2.061296 0.04598394

ERG v-ets erythroblastosis virus E26 oncogene 2.060672 0.00751355 homolog (avian)

SCPEP1 serine carboxypeptidase 1 2.060543 0.03705332

COPA coatomer protein complex, subunit alpha 2.060237 0.01659317

WDR17 WD repeat domain 17 2.059102 0.03201935

NKAIN1 #N/A 2.057883 0.03463659

DDX19B DEAD (Asp-Glu-Ala-As) box polypeptide 19B 2.057343 0.02376143

SMARCA SWI/SNF related, matrix associated, actin 2.057319 0.02557869

LI dependent regulator of chromatin, subfamily a-like

1

PCGF3 polycomb group ring finger 3 2.057016 0.01483219

CAPN2 calpain 2, (m/II) large subunit 2.056544 0.0491258

FLJ40504 keratin 18 pseudogene 2.05585 0.04756887

BRI3 brain protein 13 2.055766 0.04249244

PPP2R5C protein phosphatase 2, regulatory subunit B', 2.055208 0.02721621 gamma

GANAB Glucosidase, alpha; neutral AB 2.054564 0.04775384

TSPAN1 tetraspanin 1 2.052889 0.02243325

HACL1 2-hydroxyacyl-CoA lyase 1 2.052224 0.04582893

CCDC126 coiled-coil domain containing 126 2.05198 0.00386287

MCM9 minichromosome maintenance complex 2.051018 0.01929319 component 9

POLR2A polymerase (RNA) II (DNA directed) polypeptide 2.049273 0.01201635

A, 220kDa

MATK megakaryocyte-associated tyrosine kinase 2.048784 0.04855365

TBC1D10 #N/A 2.046411 0.04126805

A

FOXJ3 forkhead box J3 2.045612 0.02462986

KIAA184 KIAA1841 2.04433 0.02550558

1

TBC1D19 TBC1 domain family, member 19 2.043551 0.00198919 BOD1 biorientation of chromosomes in cell division 1 2.043392 0.03367415 SENP8 #N/A 2.043162 0.01143988 SLC16A4 solute carrier family 16, member 4 2.043144 0.03742794

(monocarboxylic acid transporter 5)

TMEM50 transmembrane protein 50B 2.0431 0.03853038 B

C9orf96 chromosome 9 open reading frame 96 2.039984 0.01602301

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

ENTPD1 #N/A 2.039157 0.0157279

TGFBRA transforming growth factor, beta receptor 2.039078 0.02002439

PI associated protein 1

FRMD6 FERM domain containing 6 2.038562 0.03525536 POLR3A polymerase (RNA) III (DNA directed) polypeptide 2.037793 0.04734161

A, 155kDa

NUP133 nucleoporin 133kDa 2.036795 0.03118442

ICOSLG #N/A 2.036312 0.01273721

DDIT3 DNA-damage-inducible transcript 3 2.035672 0.01260509

DULLAR dullard homolog (Xenopus laevis) 2.034606 0.02967567

D

KIAA132 KIAA1324-like 2.034493 0.00645901 4L

TEL02 TEL2, telomere maintenance 2, homolog (S. 2.033902 0.01009688 cerevisiae)

AGFG2 ArfGAP with FG repeats 2 2.031856 0.03916018

CFH complement factor H 2.030595 0.03036614

C9orf5 chromosome 9 open reading frame 5 2.030239 0.03586119

TMEM18 transmembrane protein 183 A 2.029282 0.01736117

3A

CRTAC1 #N/A 2.027223 0.01696305 HIST1H2 histone cluster 1, H2be 2.024897 0.0278084 BE

DDX10 DEAD (Asp-Glu- Ala-Asp) box polypeptide 10 2.02467 0.03369673

DCBLD2 discoidin, CUB and LCCL domain containing 2 2.023168 0.02449477

WDR54 WD repeat domain 54 2.023059 0.0430325

IGSF1 immunoglobulin superfamily, member 1 2.022907 0.0217968

FAM65A family with sequence similarity 65, member A 2.022344 0.00515737

NDUFA1 NADH dehydrogenase (ubiquinone) 1 alpha 2.021916 0.02265365

0 subcomplex, 10, 42kDa

CTPS CTP synthase 2.020961 0.0454319

PAPD4 PAP associated domain containing 4 2.019495 0.04008597

GALNT2 UDP-N-acetyl-alpha-D-galactosamine:polypeptide 2.019375 0.0343144

N-acetylgalactosaminyltransferase 2 (GalNAc-T2)

CUL7 cullin 7 2.019007 0.02526261

PLEKHG pleckstrin homology domain containing, family G 2.018739 0.0133122

2 (with RhoGef domain) member 2

SERI C5 serine incorporator 5 2.018135 0.0401226

TTC37 tetratricopeptide repeat domain 37 2.015973 0.01897095

LIMK2 LIM domain kinase 2 2.015851 0.01966932

BTBD12 #N/A 2.015237 0.03720552

FAM5B family with sequence similarity 5, member B 2.014759 0.01820992

DOCK8 dedicator of cytokinesis 8 2.014412 0.00434593

RILPL1 #N/A 2.013918 0.02071449

GLUL glutamate-ammonia ligase 2.013353 0.01359148

ALDH9A aldehyde dehydrogenase 9 family, member Al 2.013125 0.03374331

1

SQRDL sulfide quinone reductase-like (yeast) 2.012745 0.00681842 PIGN phosphatidylinositol glycan anchor biosynthesis, 2.012066 0.03637931 class N

DB U 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

EFHC1 EF-hand domain (C-terminal) containing 1 2.01 173 0.01468961 VPS13D vacuolar protein sorting 13 homolog D (S. 2.01 1571 0.01703863 cerevisiae)

AHI1 Abelson helper integration site 1 2.011165 0.04965523 ZFYVE9 zinc finger, FYVE domain containing 9 2.010537 0.03963952 MED 15 mediator complex subunit 15 2.009871 0.0046975 TARS2 threonyl-tRNA synthetase 2, mitochondrial 2.009722 0.04831308

(putative)

RNASE4 #N/A 2.009656 0.00740801

HDAC6 histone deacetylase 6 2.009034 0.02420665

ATG9B ATG9 autophagy related 9 homolog B (S. 2.008936 0.04422972 cerevisiae)

CXCL5 #N/A 2.00891 0.03149128

I PP5J inositol polyphosphate-5 -phosphatase J 2.008428 0.00203254

PEX19 peroxisomal biogenesis factor 19 2.008181 0.00973182

TRIM24 tripartite motif-containing 24 2.007807 0.03950043

TRAF3IP TRAF3 interacting protein 2 2.007532 0.01812111

2

10-Sep #N/A 2.005107 0.04938754 ELF2 E74-like factor 2 (ets domain transcription factor) 2.004646 0.01763801 FLJ20674 Hypothetical protein FLJ20674 2.004557 0.00432274 OSMR oncostatin M receptor 2.002788 0.0407116 CLEC18A C-type lectin domain family 18, member A 2.002304 0.04924147 BET1L #N/A 2.00183 0.04957609 PAOX polyamine oxidase (exo-N4-amino) 1.99911 0.00673077 PRICKLE prickle homolog 3 (Drosophila) 1.999055 0.01952605 3

HPCAL1 hippocalcin-like 1 1.998674 0.0076982

TSPAN31 tetraspanin 31 1.998064 0.04403488

KIR3DL2 killer cell immunoglobulin-like receptor, three 1.997355 0.0368632 domains, long cytoplasmic tail, 2

FBRSL1 fibrosin-like 1 1.996861 0.01347891 C17orf81 chromosome 17 open reading frame 81 1.996773 0.04433268 LOC2205 #N/A 1.996635 0.01160697 94

MAP3K12 mitogen-activated protein kinase kinase kinase 12 1.995475 0.02641934

ATP9B ATPase, class II, type 9B 1.995294 0.04583778

F8A1 #N/A 1.99508 0.04250009

ACSL1 acyl-CoA synthetase long-chain family member 1 1.995074 0.00089481

CELA3B #N/A 1.99442 0.01533788

SLC30A7 solute carrier family 30 (zinc transporter), member 1.993271 0.03666306

7

PRMT3 protein arginine methyltransferase 3 1.992162 0.00863879

PAM peptidylglycine alpha-amidating monooxygenase 1.991505 0.00094873

PDHX pyruvate dehydrogenase complex, component X 1.991377 0.04243255

ADCY3 adenylate cyclase 3 1.991273 0.00529787

FAM114A family with sequence similarity 114, member A2 1.990681 0.01035328

2

NKX3-1 NK3 homeobox 1 1.990583 0.01359758 MPPED2 metallophosphoesterase domain containing 2 1.989438 0.04218865

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Uprcgulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

WDR19 WD repeat domain 19 1.988941 0.03821171

FRAS1 Fraser syndrome 1 1.988111 0.03074444

MCCC2 Methylcrotonoyl-Coenzyme A carboxylase 2 1.986557 0.01821922

(beta)

ANO10 anoctamin lO 1.985731 0.00025163

SEMA3A sema domain, immunoglobulin domain (Ig), short 1.984479 0.00549881 basic domain, secreted, (semaphorin) 3A

SIL1 SIL1 homolog, endoplasmic reticulum chaperone 1.984176 0.0093771

(S. cerevisiae)

LONRF1 LON peptidase N- terminal domain and ring finger 1.983508 0.00345862

1

WDR85 #N/A 1.983297 0.03091787

ITFG3 integrin alpha FG-GAP repeat containing 3 1.983129 0.04260644

ERBB3 v-erb-b2 erythroblastic leukemia viral oncogene 1.981818 0.04875523 homolog 3 (avian)

PREB prolactin regulatory element binding 1.981672 0.02852565

ENPP1 ectonucleotide pyrophosphatase/phosphodiesterase 1.981336 0.01844171

1

CSPP1 centrosome and spindle pole associated protein 1 1.981269 0.04082699

SDHB succinate dehydrogenase complex, subunit B, iron 1.980256 0.00952515 sulfur (Ip)

MIF #N/A 1.979778 0.01765393

ELAC2 elaC homolog 2 (E. coli) 1.979383 0.00409566

APC adenomatous polyposis coli 1.978957 0.02642031

LOC2601 Viral DNA polymerase-transactivated protein 6 1.978739 0.04497948 0

SLC39A1 solute carrier family 39 (zinc transporter), member 1.978355 0.02888006 2 12

STX12 syntaxin l2 1.977998 0.03106077

TMEM19 transmembrane protein 198 1.977707 0.0168314

SHROOM shroom family member 3 1.977414 0.01628976 3

SGCG sarcoglycan, gamma (35kDa dystrophin-associated 1.976029 0.04872242 glycoprotein)

CD109 CD 109 molecule 1.975962 0.03780495 TRPV5 transient receptor potential cation channel, 1.975926 0.01142992 subfamily V, member 5

NFX1 nuclear transcription factor, X-box binding 1 1.974681 0.03204951

RASAL2 RAS protein activator like 2 1.974273 0.00945316

MYOIC myosin IC 1.973502 0.03292925

FAT1 FAT tumor suppressor homolog 1 (Drosophila) 1.973257 0.03471174

APP amyloid beta (A4) precursor protein 1.973232 0.03396235

TRPM6 transient receptor potential cation channel, 1.972804 0.02966632 subfamily M, member 6

CEP 192 centrosomal protein 192kDa 1.972566 0.04466506

ARHGAP Rho GTPase activating protein 18 1.971624 0.03244688

18

C14orfl #N/A 1.97125 0.03550573 ADAR adenosine deaminase, RNA-specific 1.970478 0.02323278

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

PFKFB2 6-phosphofructo-2-kinase/fructose-2,6- 1.970015 0.00399819 biphosphatase 2

RLF rearranged L-myc fusion 1.969754 0.01353227

SSFA2 sperm specific antigen 2 1.968486 0.01548873 hCG_1640 #N/A 1.966671 0.03863105

171

FOS #N/A 1.965857 0.03362548

CLMN calmin (calponin-like, transmembrane) 1.965204 0.00532298

EIF4E2 eukaryotic translation initiation factor 4E family 1.965165 0.0200992 member 2

MAML1 mastermind-like 1 (Drosophila) 1.965045 0.02968616

HIST2H4 histone cluster 2, H4a 1.964463 0.04156608

A

TMEM20 transmembrane protein 208 1.963724 0.01715938 8

MED 12 mediator complex subunit 12 1.963442 0.04534554

OPTN Optineurin 1.963237 0.02282148

EXOC7 exocyst complex component 7 1.962978 0.00819659

ZNF530 #N/A 1.962974 0.02809778

DST dystonin 1.962826 0.0356846

DOPEY 1 dopey family member 1 1.962635 0.00936706

ZNF669 zinc finger protein 669 1.962251 0.01307985

ZNF664 zinc finger protein 664 1.961938 0.02541237

TTC21B tetratricopeptide repeat domain 2 IB 1.960637 0.00300804

PPM1K protein phosphatase, Mg2+/Mn2+ dependent, IK 1.960567 0.03170998

PDE8A phosphodiesterase 8A 1.960537 0.01873747

SPDEF SAM pointed domain containing ets transcription 1.960452 0.0390656 factor

C13orf34 chromosome 13 open reading frame 34 1.960428 0.03422755 PMEPA1 prostate transmembrane protein, androgen induced 1.959469 0.03570985

1

MEDIO mediator complex subunit 10 1.9594 0.03380336

AMELX amelogenin, X-linked 1.959231 0.04580962

AGA aspartylglucosaminidase 1.958962 0.02627481

COL6A2 collagen, type VI, alpha 2 1.95896 0.03531084

UXS1 UDP-glucuronate decarboxylase 1 1.958751 0.03336713

UGCG UDP-glucose ceramide glucosyltransferase 1.958597 0.01999611

WD 93 WD repeat domain 93 1.958538 0.01358497

CPLX2 complexin 2 1.957912 0.04856893

CHFR Checkpoint with forkhead and ring finger domains 1.957518 0.01016181

S AMD 10 sterile alpha motif domain containing 10 1.956836 0.03784731

KCNH1 potassium voltage-gated channel, subfamily H 1.95678 0.01184592

(eag-related), member 1

KIAA124 KIAA1244 1.956128 0.02848508 4

SMAD7 SMAD family member 7 1.955983 0.016347

NCAPG2 non-SMC condensin II complex, subunit G2 1.955733 0.00123487

KIF13B kinesin family member 13B 1.954903 0.00695187

ZFP36L2 #N/A 1.954851 0.0013625

SIDT1 SID1 transmembrane family, member 1 1.954674 0.04160414 1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

ATXN1 ataxin l 1.954585 0.02056391 SDF4 #N/A 1.9541 0.01455397 TMEM14 transmembrane protein 144 1.954001 0.02002059 4

EIF3F eukaryotic translation initiation factor 3, subunit F 1.953937 0.04942974

CCNJ cyclin J 1.953568 0.0307558

BMP6 bone morphogenetic protein 6 1.953407 0.00565919

EXOC2 exocyst complex component 2 1.952472 0.01339535

ASB1 ankyrin repeat and SOCS box-containing 1 1.952381 0.03633353

EML2 #N/A 1.952229 0.00541735

PUM1 pumilio homolog 1 (Drosophila) 1.951866 0.0158386

LMLN leishmanolysin-like (metallopeptidase M8 family) 1.951368 0.02521616

TMEM70 transmembrane protein 70 1.950205 0.02384912

SLC25A1 solute carrier family 25, member 13 (citrin) 1.949537 0.04388595

3

FASN fatty acid synthase 1.948427 0.02462526 PCDHB16 #N/A 1.948418 0.04667535 VTN vitronectin 1.948149 0.00804688 QTRTD1 queuine tRNA-ribosyltransferase domain 1.947974 0.04351918 containing 1

UGT1A1 UDP glucuronosyltransferase 1 family, 1.947405 0.03804037 polypeptide Al

GAL Galanin prepropeptide 1.947374 0.03405624 ALG9 asparagine-linked glycosylation 9, alpha- 1,2- 1.947258 0.04996388 mannosyltransferase homolog (S. cerevisiae)

FBXL5 F-box and leucine-rich repeat protein 5 1.946953 0.03780512

DEPDC6 DEP domain containing 6 1.946724 0.02824042

TRAK2 trafficking protein, kinesin binding 2 1.946558 0.00194833

CHD3 chromodomain helicase DNA binding protein 3 1.945989 0.02579796

ANKHD1 ANKHDl-EIF4EBP3 readthrough 1.945791 0.03987177

EIF4EBP3

ZNF512 zinc finger protein 512 1.944769 0.03883459

NPFFR1 neuropeptide FF receptor 1 1.944368 0.00508591

DEN D3 DENN/MADD domain containing 3 1.943696 0.03849635

BST1 bone marrow stromal cell antigen 1 1.943471 0.01376543

BCL2L11 BCL2-like 11 (apoptosis facilitator) 1.943373 0.01340632

RASAl RAS p21 protein activator (GTPase activating 1.943062 0.01887466 protein) 1

WNT2B wingless-type MMTV integration site family, 1.942845 0.03051607 member 2B

DCLRE1 DNA cross-link repair 1C (PS02 homolog, S. 1.942843 0.01560169 C cerevisiae)

ETS2 v-ets erythroblastosis virus E26 oncogene 1.942073 0.00217845 homolog 2 (avian)

DNASE2 deoxyribonuclease II, lysosomal 1.942024 0.01200752

TRAFD1 TRAF-type zinc finger domain containing 1 1.941885 0.02871056

PEX12 #N/A 1.941744 0.04737382

LIMA1 LIM domain and actin binding 1 1.941669 0.04567907

IMPDH2 IMP (inosine 5'-monophosphate) dehydrogenase 2 1.941513 0.0365507 1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P

Symbol Change value

MYPN myopalladin 1.940856 0.00327924

BECN1 beclin 1, autophagy related 1.939624 0.03134078

TRMT12 tR A methyltransferase 12 homolog (S. 1.939237 0.0271696 cerevisiae)

WDR47 WD repeat domain 47 1.939015 0.01410477

GLS2 glutaminase 2 (liver, mitochondrial) 1.938232 0.00793526

WDFY4 WDFY family member 4 1.938099 0.03267152

OR8D2 Olfactory receptor, family 8, subfamily D, member 1.938013 0.00598943

9

NCAPD3 non-SMC condensin II complex, subunit D3 1.937119 0.04972044

FAT2 FAT tumor suppressor homolog 2 (Drosophila) 1.93697 0.00379669

ROBOl roundabout, axon guidance receptor, homolog 1 1.9367 0.03725501

(Drosophila)

FAM131C #N/A 1.936587 0.03934531

PRMT2 protein arginine methyltransferase 2 1.935965 0.01672214

ATP6V0A ATPase, H+ transporting, lysosomal VO subunit a4 1.935551 0.01584305

MY05B myosin VB 1.935376 0.00697742

TTPAL #N/A 1.934954 0.01866925

POLR1A polymerase (RNA) I polypeptide A, 194kDa 1.933999 0.01513979

RPP40 #N/A 1.933671 0.00757301

C20orfl96 chromosome 20 open reading frame 196 1.933501 0.0312781 1

SMYD4 SET and MYND domain containing 4 1.932889 0.0209559

SYNGR4 #N/A 1.932569 0.04184076

MED22 mediator complex subunit 22 1.932531 0.00073511

BCKDK #N/A 1.932472 0.03091836

CPEB4 cytoplasmic polyadenylation element binding 1.932187 0.02043112 protein 4

HOXB3 homeobox B3 1.932022 0.03389903

PDE9A phosphodiesterase 9A 1.930898 0.00997

ILKAP integrin-linked kinase-associated serine/threonine 1.930093 0.04312904 phosphatase 2C

FBX032 #N/A 1.928699 0.00876792

OSBPL11 oxysterol binding protein-like 11 1.927606 0.0141209

ZMYM3 #N/A 1.92728 0.0069445

ZZEF1 zinc finger, ZZ-type with EF-hand domain 1 1.927149 0.01667368

ORC1L origin recognition complex, subunit 1-like (yeast) 1.926446 0.04566535

PRR1 proline rich 14 1.925862 0.03753863

SRBD1 SI RNA binding domain 1 1.925412 0.04260049

GNA12 guanine nucleotide binding protein (G protein) 1.924993 0.00879528 alpha 12

MAPKAP mitogen-activated protein kinase-activated protein 1.924941 0.02799185

K2 kinase 2

HMGCR 3 -hydroxy-3 -methyl glutaryl-CoA reductase 1.924533 0.03145288

SGEF Src homology 3 domain-containing guanine 1.924356 0.02658412 nucleotide exchange factor

IAA074 KIAA0748 1.923943 0.00099504 o

o

GPD2 glycerol-3 -phosphate dehydrogenase 2 1.923915 0.02166602

(mitochondrial)

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

PRAME Preferentially expressed antigen in melanoma 1.923708 0.03028361

DFNA5 deafness, autosomal dominant 5 1.923557 0.01859714

ZNF764 zinc finger protein 764 1.92335 0.01449098

VPS13C vacuolar protein sorting 13 homolog C (S. 1.923146 0.0079469 cerevisiae)

FAT4 FAT tumor suppressor homolog 4 (Drosophila) 1.922318 0.02481653

COQ9 coenzyme Q9 homolog (S. cerevisiae) 1.921458 0.01957612

ABLIM2 #N/A 1.920353 0.04876135

IL11RA interleukin 11 receptor, alpha 1.919985 0.01904984

PPP2R3A protein phosphatase 2 (formerly 2 A), regulatory 1.919842 0.04499205 subunit B", alpha

CNN3 calponin 3, acidic 1.919589 0.01326361

GNE glucosamine (UDP-N-acetyl)-2-epimerase/N- 1.919289 0.01680644 acetylmannosamine kinase

DPY19L3 dpy-19-like 3 (C. elegans) 1.919167 0.01045808

LRP12 #N/A 1.919116 0.01579065

EP400 E1A binding protein p400 1.918726 0.01295417

ZNF782 zinc finger protein 782 1.917801 0.04972236

SLC9A9 Solute carrier family 9 (sodium/hydrogen 1.917704 0.02162075 exchanger), member 9

C8orf82 chromosome 8 open reading frame 82 1.917694 0.03256964

EEF2 eukaryotic elongation factor-2 kinase 1.917587 0.00471823

CLN3 ceroid-lipofuscinosis, neuronal 3 1.916668 0.01064925

NEDD4L Neural precursor cell expressed, developmentally 1.916554 0.03460953 down-regulated 4-like

CLDN11 #N/A 1.91655 0.00517708

TAS1R1 taste receptor, type 1, member 1 1.916462 0.02473007

MCOLN3 mucolipin 3 1.916366 0.04747661

KRT85 #N/A 1.916104 0.01633036

NRDl nardilysin (N-arginine dibasic convertase) 1.915686 0.00426155

LMBR1L limb region 1 homolog (mouse)-like 1.915079 0.00394172

NPTN neuroplastin 1.914001 0.03145238

ZFYVE21 zinc finger, FYVE domain containing 21 1.913658 0.04051534

C1QTNF6 Clq and tumor necrosis factor related protein 6 1.913538 0.03897987

KIF13A kinesin family member 13A 1.913366 0.02177671

PIAS3 protein inhibitor of activated STAT, 3 1.912841 0.01839942

ZNF767 zinc finger family member 767 1.911872 0.02293369

BRWD2 Bromodomain and WD repeat domain containing 1.911198 0.02211182

2

FTSJ3 FtsJ homolog 3 (E. coli) 1.910659 0.0455875

LMBR1 limb region 1 homolog (mouse) 1.909391 0.03414052

KAT2B K(lysine) acetyltransferase 2B 1.909382 0.04214866

NODI nucleotide-binding oligomerization domain 1.909185 0.02204213 containing 1

CTSB cathepsin B 1.909121 0.0417279

THBD #N/A 1.908547 0.03756521

TLE1 transducin-like enhancer of split 1 (E(spl) 1.908118 0.04074464 homolog, Drosophila)

PCOLCE2 procollagen C-endopeptidase enhancer 2 1.90722 0.00629512

HERPUD HERPUD family member 2 1.906892 0.02572507

DBU 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

2

BAZ2B bromodomain adjacent to zinc finger domain, 2B 1.906596 0.03547602

OSGEP O-sialoglycoprotein endopeptidase 1.906341 0.02084514

FM03 flavin containing monooxygenase 3 1.906176 0.04859884

STRADB STE20-related kinase adaptor beta 1.906072 0.0150799

PNPLA4 patatin-like phospholipase domain containing 4 1.905541 0.04312986

CNOT2 CCR4-NOT transcription complex, subunit 2 1.90473 0.03898023

XRCC6B XRCC6 binding protein 1 1.90444 0.04717261

PI

IQSEC1 IQ motif and Sec7 domain 1 1.903414 0.02704439

YRDC yrdC domain containing (E. coli) 1.90296 0.00382355

C15orf39 chromosome 15 open reading frame 39 1.902875 0.00696556

C20orfl2 chromosome 20 open reading frame 12 1.90269 0.00583575

APBB2 amyloid beta (A4) precursor protein-binding, 1.90255 0.03919277 family B, member 2

CCDC138 coiled-coil domain containing 138 1.902246 0.02695231

FAM117B family with sequence similarity 117, member B 1.901772 0.01897273

P2RY6 #N/A 1.901728 0.01023842

ACAA1 #N/A 1.901316 0.01060867

BBX bobby sox homolog (Drosophila) 1.900909 0.01500846

PAXIP1 PAX interacting (with transcription-activation 1.900506 0.03772507 domain) protein 1

TRIO triple functional domain (PTPRF interacting) 1.899678 0.0063113 HPS5 Hermansky-Pudlak syndrome 5 1.899503 0.00150148 PLK2 polo-like kinase 2 (Drosophila) 1.89847 0.02392197 MYBBP1 MYB binding protein (PI 60) la 1.897963 0.01696392

A

SDR42E1 #N/A 1.897472 0.0275267

GMDS GDP-mannose 4,6-dehydratase 1.89713 0.00751708

KIF16B kinesin family member 16B 1.896905 0.02455102

PHF12 #N/A 1.896855 0.04395523

ZNF565 #N/A 1.896339 0.01266803

SLC6A13 solute carrier family 6 (neurotransmitter 1.896275 0.04426482 transporter, GAB A), member 13

FAM57A family with sequence similarity 57, member A 1.895465 0.00415853

FAM115A family with sequence similarity 115, member A 1.895377 0.02770417

DVL2 dishevelled, dsh homolog 2 (Drosophila) 1.895338 0.01917641

THTPA #N/A 1.89522 0.01954414

TIMP3 TIMP metallopeptidase inhibitor 3 1.895168 0.04628139

CHM choroideremia (Rab escort protein 1) 1.894444 0.0046574

TESSP2 Testis serine protease 2 1.893707 0.02721581

UROC1 urocanase domain containing 1 1.893215 0.00237883

RNASEN ribonuclease type III, nuclear 1.892763 0.01417458

GPR98 G protein-coupled receptor 98 1.892624 0.01326612

RPL22 ribosomal protein L22 1.892541 0.00202954

COL27A1 collagen, type XXVII, alpha 1 1.892027 0.03196172

IQGAP1 IQ motif containing GTPase activating protein 1 1.891881 0.04620746

GNAZ guanine nucleotide binding protein (G protein), 1.890976 0.03305613 alpha z polypeptide

PCTK3 PCTAIRE protein kinase 3 1.889217 0.04404937

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

CACNG4 #N/A 1.888787 0.04519699

C14orfl 79 chromosome 14 open reading frame 179 1.888348 0.04330074

PAPSS2 3'-phosphoadenosine 5'-phosphosulfate synthase 2 1.888307 0.02252546

APAF1 apoptotic peptidase activating factor 1 1.887923 0.02230552

CBX4 chromobox homolog 4 (Pc class homolog, 1.887855 0.04890595

Drosophila)

ZNF544 zinc finger protein 544 1.887464 0.03641561 SMOC1 SPARC related modular calcium binding 1 1.88737 0.02939271 RASGEF1 RasGEF domain family, member 1 A 1.887156 0.03052987 A

DCTD dCMP deaminase 1.887005 0.0238736

MAST2 microtubule associated serine/threonine kinase 2 1.886936 0.0432921

SLIT2 slit homolog 2 (Drosophila) 1.88609 0.01870651

FGD5 FYVE, RhoGEF and PH domain containing 5 1.886022 0.00617006

MBOAT1 membrane bound O-acyltransferase domain 1.886004 0.04598058 containing 1

DNAJC13 DnaJ (Hsp40) homolog, subfamily C, member 13 1.885103 0.00977761 MET met proto-oncogene (hepatocyte growth factor 1.884783 0.02601866 receptor)

ALKBH8 alkB, alkylation repair homolog 8 (E. coli) 1.883827 0.03014588

FADS2 Fatty acid desaturase 2 1.883525 0.0107778

RBM5 RNA binding motif protein 5 1.882901 0.00067389

ZNF266 zinc finger protein 266 1.882654 0.01663134

ARMC10 armadillo repeat containing 10 1.881877 0.00093444

RNF4 ring finger protein 4 1.881628 0.00674585

PCNX pecanex homolog (Drosophila) 1.880739 0.0295066

MEGF11 multiple EGF-like-domains 11 1.880138 0.00593701

DGKD diacylglycerol kinase, delta 130kDa 1.879797 0.01825987

SFRS8 splicing factor, arginine/serine-rich 8 (suppressor- 1.879646 0.03974937 of-white-apricot homolog, Drosophila)

DNTTIP1 deoxynucleotidyltransferase, terminal, interacting 1.87932 0.0331851 protein 1

C16orf70 chromosome 16 open reading frame 70 1.878726 0.04099413

NCRNAO non-protein coding RNA 105 1.878536 0.00912885

0105

SMYD3 SET and MYND domain containing 3 1.877778 0.03988187

KRTAP5- Keratin associated protein 5-9 1.877195 0.0195685

9

ATP6V1B ATPase, H+ transporting, lysosomal 56/58kDa, 1.877107 0.02190657 1 VI subunit Bl

CCDC114 coiled-coil domain containing 1 14 1.876977 0.00807659

VEGFA vascular endothelial growth factor A 1.876933 0.03850214

PAIP1 poly(A) binding protein interacting protein 1 1.876158 0.0161617

COL15A1 collagen, type XV, alpha 1 1.875908 0.03575299

MIF4GD MIF4G domain containing 1.87574 0.04359308

EIF4G1 eukaryotic translation initiation factor 4 gamma, 1 1.874885 0.03844546

BLM Bloom syndrome, RecQ helicase-like 1.874742 0.03470524

SGK196 protein kinase-like protein SgKl 96 1.87418 0.02399226

HSD1 1B2 hydroxysteroid (1 1 -beta) dehydrogenase 2 1.873772 0.019067

MRPS27 Mitochondrial ribosomal protein S27 1.873698 0.03964852

DB l/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

GPR137B G protein-coupled receptor 137B 1.872329 0.04698515

MANBA mannosidase, beta A, lysosomal 1.872158 0.02873341

LY6G5B #N/A 1.871825 0.03504443

AGXT2L2 alanine-glyoxylate aminotransferase 2-like 2 1.871678 0.01131574

I IRH3 histamine receptor H3 1.871571 0.03851706

ACTR8 ARP8 actin-related protein 8 homolog (yeast) 1.871091 0.02472616

FAM82A2 family with sequence similarity 82, member A2 1.870417 0.00217246

SYNE2 spectrin repeat containing, nuclear envelope 2 1.870394 0.01818784

OCRL oculocerebrorenal syndrome of Lowe 1.869419 0.01895175

CRYGA #N/A 1.869382 0.01865733

ACAD 11 acyl-CoA dehydrogenase family, member 11 1.868666 0.04806959

ZKSCAN zinc finger with KRAB and SCAN domains 3 1.867916 0.00078552

3

GALNT11 UDP-N-acetyl-alpha-D-galactosamine:polypeptide 1.867621 0.03529265

N-acetylgalactosaminyltransferase 11 (GalNAc-

Tl l)

PTPN3 protein tyrosine phosphatase, non-receptor type 3 1.867552 0.03410731

CDC42BP CDC42 binding protein kinase alpha (DMPK-like) 1.867402 0.0258652

A

IGHG1 Immunoglobulin heavy constant gamma 1 (Glm 1.867311 0.03631848 marker)

VAV3 vav 3 guanine nucleotide exchange factor 1.86696 0.01798735 STEAP3 STEAP family member 3 1.8661 0.00278677 ST5 suppression of tumorigenicity 5 1.865484 0.02806159 WWP1 WW domain containing E3 ubiquitin protein 1.865067 0.03347901 ligase 1

C9orf93 chromosome 9 open reading frame 93 1.864745 0.00700856 MTR 5-methyltetrahydrofolate-homocysteine 1.864588 0.02616119 methyltransferase

ZNF509 Zinc finger protein 509 1.86424 0.04624603

C14orfi02 chromosome 14 open reading frame 102 1.864093 0.00110785

CAT catalase 1.863965 0.02233098

SORT1 sortilin 1 1.863904 0.00679365

GAL3ST2 galactose-3-O-sulfotransferase 2 1.863453 0.03871831

WDFY3 WD repeat and FYVE domain containing 3 1.862532 0.02303744

OR2T3 Olfactory receptor, family 2, subfamily T, member 1.862085 0.0318299

3

GTF2H4 general transcription factor IIH, polypeptide 4, 1.861583 0.032341 3

52kDa

CCDC23 coiled-coil domain containing 23 1.861564 0.03409132

ADCY9 adenylate cyclase 9 1.86108 0.00469599

POLE polymerase (DNA directed), epsilon 1.860575 0.0261064

DDX50 DEAD (Asp-Glu- Ala-Asp) box polypeptide 50 1.860454 0.04904022

TRAPPC9 #N/A 1.859816 0.02729074

SORBS1 Sorbin and SH3 domain containing 1 1.859486 0.02920018

FRMD3 FERM domain containing 3 1.85812 0.03794642

DDX28 #N/A 1.85746 0.00748255

HTT huntingtin 1.857258 0.00520267

POMT2 protein-O-mannosyltransferase 2 1.856647 0.03166017

HSD17B8 hydroxysteroid (17-beta) dehydrogenase 8 1.856477 0.0175483 1/ 69437516.1 Supplemental Table 2 Gene Transcripts TJpregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

ALPP alkaline phosphatase, placental (Regan isozyme) 1.855804 0.01259775

SERPINB serpin peptidase inhibitor, clade B (ovalbumin), 1.855648 0.03528406

1 member 1

TTC28 tetratricopeptide repeat domain 28 1.854215 0.02108348 FAM86B1 family with sequence similarity 86, member Bl 1.854169 0.0460832 GUCY1B guanylate cyclase 1 , soluble, beta 2 1.854083 0.0275397 2

ACTR1A ARP1 actin-related protein 1 homolog A, 1.853348 0.03328455 centractin alpha (yeast)

TLR5 toll-like receptor 5 1.853333 0.03051119

BRCC3 BRCAl/BRCA2-containing complex, subunit 3 1.852606 0.03453754

HI ATI hippocampus abundant transcript 1 1.852532 0.0176408

ARMCX6 armadillo repeat containing, X-linked 6 1.852514 0.03240179

NBR1 neighbor of BRCA1 gene 1 1.852291 0.04358667

TNIK TRAF2 and NCK interacting kinase 1.852078 0.03009865

ALCAM activated leukocyte cell adhesion molecule 1.851831 0.00018223

ITPRIPL1 #N/A 1.851726 0.01392265

ESRP2 epithelial splicing regulatory protein 2 1.85125 0.00626719

ATP1A2 ATPase, Na+/K+ transporting, alpha 2 polypeptide 1.851162 0.04430596

ACP2 acid phosphatase 2, lysosomal 1.851041 0.00870894

MED12L mediator complex subunit 12-like 1.850755 0.01680082

RBM47 RNA binding motif protein 47 1.850449 0.01839222

IL2RB interleukin 2 receptor, beta 1.85013 0.02832439

RNF135 ring finger protein 135 1.849442 0.01864435

PHIP Pleckstrin homology domain interacting protein 1.849173 0.04670099

TYW1 tRNA-yW synthesizing protein 1 homolog (S. 1.84902 0.0295001 cerevisiae)

CCDC83 coiled-coil domain containing 83 1.848439 0.00716519

KIAA074 KIAA0746 protein 1.848377 0.04864065

6

1-Sep #N/A 1.848267 0.04618615 MOV10L MovlOll, Moloney leukemia virus 10-like 1, 1.848163 0.02783992 1 homolog (mouse)

GSTM4 glutathione S -transferase mu 4 1.84803 0.00686783

KIF12 kinesin family member 12 1.847663 0.01009945

PLAGL1 pleiomorphic adenoma gene-like 1 1.847369 0.03548168

CAPN1 calpain 1, (mu/I) large subunit 1.846754 0.04642925

OBFC1 oligonucleotide/oligosaccharide-binding fold 1.846418 0.0466534 containing 1

IFT172 intraflagellar transport 172 homolog 1.846383 0.03441771

(Chlamydomonas)

AGL amylo-alpha-1, 6-glucosidase, 4-alpha- 1.846345 0.02053249 glucanotransferase

CENPT centromere protein T 1.845845 0.00201983

EPB49 erythrocyte membrane protein band 4.9 (dematin) 1.845428 0.00956853

TLR9 toll-like receptor 9 1.845098 0.02451265

HOXC10 #N/A 1.844827 0.04141346

LIN54 lin-54 homolog (C. elegans) 1.844811 0.02042053

ATAD3C ATPase family, AAA domain containing 3C 1.844768 0.03050448

ACP6 acid phosphatase 6, lysophosphatidic 1.844688 0.02891276

DB1/ 694375 I6.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

ASAP3 ArfGAP with SH3 domain, ankyrin repeat and PH 1.84451 0.03401894 domain 3

WNK2 WNK lysine deficient protein kinase 2 1.843708 0.00016938 ITGAV integrin, alpha V (vitronectin receptor, alpha 1.842934 0.04834292 polypeptide, antigen CD51)

HTRA2 HtrA serine peptidase 2 1.842614 0.04774984

FBN2 fibrillin 2 1.841767 0.01227486

TM9SF4 transmembrane 9 superfamily protein member 4 1.841715 0.01879455

F2RL2 #N/A 1.841701 0.04986855

CSTF2 cleavage stimulation factor, 3' pre-RNA, subunit 2, 1.841567 0.02747869

64kDa

HHAT hedgehog acyltransferase 1.839619 0.02416417 FOXF2 forkhead box F2 1.839498 0.00811451 TNKS2 tankyrase, TRF1 -interacting ankyrin-related ADP- 1.839248 0.04496397 ribose polymerase 2

RILPL2 Rab interacting lysosomal protein-like 2 1.838902 0.00996151

C19orfl5 Chromosome 19 open reading frame 15 1.838587 0.04290152

FAM125A #N/A 1.837462 0.00701827

FAM73A family with sequence similarity 73, member A 1.83721 0.02226641

CPSF3L cleavage and polyadenylation specific factor 3 -like 1.837104 0.02063626

IQCK IQ motif containing K 1.836879 0.01496829

GNA14 #N/A 1.836489 0.01469786

RALGPS1 Ral GEF with PH domain and SH3 binding motif 1.836329 0.01923287

1

DBT dihydrolipoamide branched chain transacylase E2 1.836241 0.01951718

NAV2 neuron navigator 2 1.835983 0.04928384

MITF microphthalmia-associated transcription factor 1.835952 0.03068625

ELL2 elongation factor, RNA polymerase II, 2 1.835366 0.02073358

SCNN1B sodium channel, nonvoltage-gated 1, beta 1.835334 0.01750623

FZD7 #N/A 1.83521 0.0115498

MAPK12 mitogen-activated protein kinase 12 1.835192 0.02403095

IGSF10 immunoglobulin superfamily, member 10 1.835125 0.01577639

GPATCH G patch domain containing 4 1.834496 0.00899436

4

SMPD4 sphingomyelin phosphodiesterase 4, neutral 1.834372 0.00439255 membrane (neutral sphingomyelinase-3)

B4GALT2 UDP-Gal:betaGlcNAc beta 1,4- 1.8338 0.00400978 galactosyltransferase, polypeptide 2

TMEM39 transmembrane protein 39A 1.833209 0.02356189 A

PPP2R2C protein phosphatase 2, regulatory subunit B, 1.833122 0.00845584 gamma

MYBPH myosin binding protein H 1.833019 0.00486753

BBS1 Bardet-Biedl syndrome 1 1.8329 0.045751

LOCIOOI #N/A 1.832811 0.00342114

30131

AHCY adenosylhomocysteinase 1.832479 0.02432264

EXOSC10 exosome component 10 1.832263 0.04306411

GJC2 gap junction protein, gamma 2, 47kDa 1.832077 0.03543578

AHCTF1 AT hook containing transcription factor 1 1.83198 0.037359631/ 6943751₆.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P

Symbol Change value

GSN gelsolin 1.831593 0.04413044

ATR attractin 1.831417 0.0236229

R F44 Ring finger protein 44 1.831055 0.03914601

PFN2 profilin 2 1.83014 0.02326769

LRLE1 liver-related low express protein 1 1.829773 0.02418802

GIT2 G protein-coupled receptor kinase interacting 1.829511 0.0311222

ArfGAP 2

ΓΝΡΡ4Α inositol polyphosphate-4-phosphatase, type I, 1.828306 0.03231606

107kDa

SSBP4 single stranded DNA binding protein 4 1.827991 0.0091075

KLK14 kallikrein-related peptidase 14 1.827705 0.03124541

RTN2 #N/A 1.827064 0.01318014

CISH cytokine inducible SH2-containing protein 1.827041 0.03183502

CLSTN2 calsyntenin 2 1.826481 0.0373253

C9orf3 Chromosome 9 open reading frame 3 1.826206 0.02088969

RORA RAR-related orphan receptor A 1.825839 0.01004205

ZNF692 zinc finger protein 692 1.8258 0.04823366

PAN2 PAN2 poly(A) specific ribonuclease subunit 1.825211 0.03779317 homolog (S. cerevisiae)

IFIH1 interferon induced with helicase C domain 1 1.824823 0.04845467

GPN1 GPN-loop GTPase 1 1.823987 0.03073224

SIPA1L1 signal-induced proliferation-associated 1 like 1 1.823875 0.0169873

RI T1 RAD50 interactor 1 1.82387 0.039958

RGS20 regulator of G-protein signaling 20 1.82288 0.02277215

ZNF236 zinc finger protein 236 1.822775 0.04724938

PHF14 PHD finger protein 14 1.822563 0.03727438

KIF2C kinesin family member 2C 1.82231 0.018931

PLEC1 Plectin 1, intermediate filament binding protein 1.821867 0.04362901

500kDa

SLC20A1 solute carrier family 20 (phosphate transporter), 1.821633 0.01516049 member 1

CNOT8 CCR4-NOT transcription complex, subunit 8 1.821121 0.02498699

RAP1GD RAP1, GTP-GDP dissociation stimulator 1 1.819878 0.01679424

¾ 1

SACM1L SACl suppressor of actin mutations 1 -like (yeast) 1.819681 0.00093656

SMG5 Smg-5 homolog, nonsense mediated mRNA decay 1.819608 0.01248203 factor (C. elegans)

CADPS Ca++-dependent secretion activator 1.819099 0.01745439

CLYBL citrate lyase beta like 1.819068 0.03252962

SCCPDH saccharopine dehydrogenase (putative) 1.818406 1.08E-05

METRNL meteorin, glial cell differentiation regulator-like 1.817181 0.02789795

CAMKK2 calcium/calmodulin-dependent protein kinase 1.817056 0.02728463 kinase 2, beta

MCM3AP minichromosome maintenance complex 1.816833 0.01036449 component 3 associated protein

URG4 Up-regulated gene 4 1.816744 0.03609274

ULK2 unc-51-like kinase 2 (C. elegans) 1.816684 0.01404583

STAB1 stabilin 1 1.816028 0.03390585

KDELC1 KDEL (Lys-Asp-Glu-Leu) containing 1 1.815854 0.03640204

EHHADH enoyl-CoA, hydratase/3 -hydroxy acyl Co A 1.815128 0.01072486

B l/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

dehydrogenase

GOLPH3 golgi phosphoprotein 3 (coat-protein) 1.814714 0.02678242

ARSB arylsulfatase B 1.814591 0.0476001

TTL tubulin tyrosine ligase 1.814429 0.02900906

CDC23 Cell division cycle 23 homo log (S. cerevisiae) 1.814312 0.01424556

NLN neurolysin (metallopeptidase M3 family) 1.814047 0.00363452

CDKN2A #N/A 1.813664 0.00782587

SEC14L5 SEC14-like 5 (S. cerevisiae) 1.813525 0.00778707

LOC1584 #N/A 1.813506 0.02379264

35

RNF160 ring finger protein 160 1.81331 0.01364145

VPS13B vacuolar protein sorting 13 homolog B (yeast) 1.813221 0.02323946

AXL AXL receptor tyrosine kinase 1.812906 0.01483759

C2orfl6 chromosome 2 open reading frame 16 1.812404 0.00257035

DI030S #N/A 1.812199 0.02990504

DRG2 developmentally regulated GTP binding protein 2 1.812069 0.01854784

XAB2 XPA binding protein 2 1.811657 0.02446796

XP07 exportin 7 1.81 1431 0.02173881

DOCK5 dedicator of cytokinesis 5 1.811424 0.03101188

ZSCAN16 zinc finger and SCAN domain containing 16 1.810978 0.02805285

GSDMA #N/A 1.810932 0.04439628

KIAA031 KIAA0319 1.810581 0.04796698

9

PCCB propionyl CoA carboxylase, beta polypeptide 1.81017 0.03327504

DARS2 aspartyl-tRNA synthetase 2, mitochondrial 1.809934 0.0004163

ZNRF4 #N/A 1.809753 0.0418607

NOL6 nucleolar protein family 6 (RNA-associated) 1.809392 0.01903122

BAIAP3 BAI1 -associated protein 3 1.808624 0.02837442

SLC25A1 solute carrier family 25 (mitochondrial carrier, 1.808516 0.04836052

2 Aralar), member 12

UFSP2 #N/A 1.808457 0.02242258

ABO #N/A 1.808305 0.01404044

C17orf58 chromosome 17 open reading frame 58 1.808026 0.00737566

CERCAM cerebral endothelial cell adhesion molecule 1.807599 0.04245661

FNDC3B fibronectin type III domain containing 3B 1.807337 0.04828007

LPHN1 latrophilin 1 1.807313 0.03455603

STOX1 storkhead box 1 1.807307 0.04072721

HPS3 Hermansky-Pudlak syndrome 3 1.806824 0.00162527

ACAD9 acyl-CoA dehydrogenase family, member 9 1.806784 0.0371985

C2 complement component 2 1.80667 0.03022582

SLC2A13 solute carrier family 2 (facilitated glucose 1.806614 0.03103435 transporter), member 13

RARS2 arginyl-tRNA synthetase 2, mitochondrial 1.805822 0.00425774 GDPD3 glycerophosphodiester phosphodiesterase domain 1.805808 0.0364083 containing 3

CAMK2G calcium/calmodulin-dependent protein kinase II 1.805609 0.04464108 gamma

ZNF641 zinc finger protein 641 1.805397 0.03755286 NFAT5 nuclear factor of activated T-cells 5, toniciry- 1.80533 0.02591485 responsive

1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value

RICTOR RPTOR independent companion of MTOR, 1.8052 0.01457283 complex 2

EPB41 erythrocyte membrane protein band 4.1 1.804925 0.02384749

(elliptocytosis 1, RH-linked)

TMEM10 transmembrane protein 104 1.80478 0.01729592 4

CD70 #N/A 1.804706 0.02510777 RPS6KA2 ribosomal protein S6 kinase, 90kDa, polypeptide 2 1.804574 0.0184449 SLC39A1 #N/A 1.804555 0.01947493 1

CTSL2 #N/A 1.804045 0.00453175

USP11 ubiquitin specific peptidase 11 1.803911 0.01986362

KLHL5 Kelch-like 5 (Drosophila) 1.80375 0.04121789

OPA1 optic atrophy 1 (autosomal dominant) 1.803711 0.03903617

SLC47A2 solute carrier family 47, member 2 1.803291 0.03449051

PKN1 protein kinase l 1.803225 0.02628179

TMTC1 transmembrane and tetratricopeptide repeat 1.802521 0.04406318 containing 1

CLCN6 chloride channel 6 1.802064 0.01008228

TBR1 T-box, brain, 1 1.801116 0.04777212

EPHB2 EPH receptor B2 1.800882 0.00867104

PUS3 #N/A 1.80086 0.01529983

SHPK sedoheptulokinase 1.800252 0.00027963

OSBPL9 Oxysterol binding protein-like 9 1.799943 0.00284758

KIAA132 KIAA1324 1.799673 0.01824525

4

RBM41 RNA binding motif protein 41 1.799437 0.03296399 PITPNM2 phosphatidylinositol transfer protein, membrane- 1.799147 0.03440953 associated 2

STAMBP STAM binding protein-like 1 1.798892 0.04856885 LI

PDLIM5 PDZ and LIM domain 5 1.79811 0.01328438

PDDC1 Parkinson disease 7 domain containing 1 1.797687 0.02161418

TTC3 tetratricopeptide repeat domain 3 1.797303 0.02193066

FLJ1 1235 #N/A 1.797278 0.04835643

SERTAD1 #N/A 1.797206 0.03107296

Clorfl44 chromosome 1 open reading frame 144 1.797013 0.00876496

NCAPH non-SMC condensin I complex, subunit H 1.796877 0.02573221

VSIG6 #N/A 1.796635 0.01654433

KIF20A kinesin family member 20A 1.796555 0.00619896

KIAA052 KIAA0528 1.796529 0.04915525

ZNF793 #N/A 1.796318 0.00894016

NOG #N/A 1.796189 0.02642183

COPS7B COP9 constitutive photomorphogenic homolog 1.795644 0.00171403 subunit 7B (Arabidopsis)

CYYR1 Cysteine/tyrosine-rich 1 1.795609 0.02061148

ALS2 Amyotrophic lateral sclerosis 2 (juvenile) 1.795276 0.00416629

STK24 serine/threonine kinase 24 (STE20 homolog, 1.794633 0.04565266 yeast)

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P

Symbol Change value

HDHD2 haloacid dehalogenase-like hydrolase domain 1.794609 0.0439966 containing 2

ATP1B1 ATPase, Na+/K+ transporting, beta 1 polypeptide 1.794504 0.04608723

C17orf57 chromosome 17 open reading frame 57 1.794479 0.00928227

USP4 ubiquitin specific peptidase 4 (proto-oncogene) 1.794435 0.04240151

PPM1M protein phosphatase, Mg2+/Mn2+ dependent, 1M 1.794264 0.03533697

TNFRSF1 Tumor necrosis factor receptor superfamily, 1.794187 0.02680733

9 member 19

NAGK #N/A 1.793923 0.00154956

MKLN1 muskelin 1, intracellular mediator containing kelch 1.793833 0.00447919 motifs

ZNF561 zinc finger protein 561 1.793275 0.03392283

PCYT2 phosphate cytidylyltransferase 2, ethanolamine 1.792846 0.01623884

TMEM18 transmembrane protein 185 A 1.79283 0.02359851

J ^r Av

TMIGD1 transmembrane and immunoglobulin domain 1.792592 0.01374157 containing 1

TRIM69 tripartite motif-containing 69 1.792487 0.03262148

RAB3GA RAB3 GTPase activating protein subunit 2 (non- 1.792358 0.04858857

P2 catalytic)

ANK1 ankyrin 1, erythrocytic 1.792161 0.048551 1

PRKX protein kinase, X-linked 1.792078 0.02142469

RBM23 #N/A 1.791969 0.0206475

EIF2C4 eukaryotic translation initiation factor 2C, 4 1.791931 0.03041025

C13orfl5 Chromosome 13 open reading frame 15 1.791746 0.0365939

SPDYE7P speedy homolog E7 (Xenopus laevis), pseudogene 1.791364 0.00311628

SLC6A11 solute carrier family 6 (neurotransmitter 1.791296 0.02376178 transporter, GABA), member 11

C3orf75 chromosome 3 open reading frame 75 1.791217 0.04476106

AGK acylglycerol kinase 1.791188 0.02184074

LIMS2 LIM and senescent cell antigen-like domains 2 1.791155 0.03239708

FAM40A family with sequence similarity 40, member A 1.7911 14 0.04260628

BIRC6 baculoviral IAP repeat-containing 6 1.791019 0.04970096

STRN striatin, calmodulin binding protein 1.790869 0.00103203

RBMS1 RNA binding motif, single stranded interacting 1.790598 0.00484691 protein 1

PRKCA protein kinase C, alpha 1.790567 0.02417993

DGCR6L #N/A 1.790378 0.02948803

KCTD8 potassium channel tetramerisation domain 1.789556 0.03121183 containing 8

NFKBIL2 nuclear factor of kappa light polypeptide gene 1.789224 0.01393889 enhancer in B-cells inhibitor-like 2

SHKBP1 SH3KBP1 binding protein 1 1.789197 0.01337287

PCDHB5 protocadherin beta 5 1.788989 0.04106313

POP1 processing of precursor 1, ribonuclease P/MRP 1.788281 0.02037732 subunit (S. cerevisiae)

ARFGEF2 ADP-ribosylation factor guanine nucleotide- 1.788048 0.04903073 exchange factor 2 (brefeldin A-inhibited)

IL11 interleukin 11 1.78803 0.04701437

OR8G5 #N/A 1.78788 0.01935812 1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

EIF2C1 eukaryotic translation initiation factor 2C, 1 1.787546 0.03013723

C7orf47 chromosome 7 open reading frame 47 1.787392 0.01406517

LGALS3 lectin, galactoside-binding, soluble, 3 1.786219 0.04531611

ATCAY #N/A 1.785867 0.02441094

CCDC21 coiled-coil domain containing 21 1.785799 0.01918401

STX1A syntaxin 1A (brain) 1.785679 0.02118002

RP4- #N/A 1.785668 0.0119943

692D3.1

SNX25 sorting nexin 25 1.78541 0.02564642

PLCB4 phospholipase C, beta 4 1.78505 0.02860976

WASH2P WAS protein family homolog 2 pseudogene 1.784848 0.00363915

SPARCL1 SPARC-like 1 (hevin) 1.784575 0.00678883

PI4KA phosphatidylinositol 4-kinase, catalytic, alpha 1.78394 0.041 19075

LILRA6 leukocyte immunoglobulin-like receptor, 1.783197 0.0073758 subfamily A (with TM domain), member 6

TMPRSS1 transmembrane protease, serine 1 IB 1.782781 0.04890759 IB

SH2D4A SH2 domain containing 4A 1.782601 0.00558183 CA3 carbonic anhydrase III, muscle specific 1.782466 0.04586045

ATG16L1 ATG16 autophagy related 16-like 1 (S. cerevisiae) 1.782453 0.02898332

GIGYF2 GRB10 interacting GYF protein 2 1.782209 0.04126325

Clorf57 chromosome 1 open reading frame 57 1.782172 0.03608043

CNTNAP contactin associated protein-like 4 1.782093 0.0035102

4

KPNA6 karyopherin alpha 6 (importin alpha 7) 1.781923 0.0310852

HERC5 hect domain and RLD 5 1.781794 0.00317627

PGM2 Phosphoglucomutase 2 1.781686 0.02399861

DGKG diacylglycerol kinase, gamma 90kDa 1.781287 0.01284394

RFC1 replication factor C (activator 1) 1, 145kDa 1.780866 0.03247922

HECTD2 HECT domain containing 2 1.780455 0.00275198

NCRNAO #N/A 1.780057 0.02102031

0153

PER2 period homolog 2 (Drosophila) 1.779887 0.04286856

KIAA171 KIAA1715 1.779871 0.01240973

5

BICD2 bicaudal D homolog 2 (Drosophila) 1.779762 0.0003449

AP1B1 adaptor-related protein complex 1 , beta 1 subunit 1.779553 0.01993621

FTSJD2 FtsJ methyltransferase domain containing 2 1.779443 0.04459761

C12orf40 #N/A 1.779386 0.02461062

NOC4L nucleolar complex associated 4 homolog (S. 1.77938 0.00519869 cerevisiae)

C9orf72 chromosome 9 open reading frame 72 1.779325 0.00116813

LASP1 LIM and SH3 protein 1 1.779305 0.02397077

INTS10 integrator complex subunit 10 1.779159 0.03963764

FHOD1 formin homology 2 domain containing 1 1.778196 0.01399849

C8B complement component 8, beta polypeptide 1.778159 0.03169858

C3orf24 chromosome 3 open reading frame 24 1.778132 0.00908447

ZNF621 #N/A 1.778004 0.00522172

WIPI2 WD repeat domain, phosphoinositide interacting 2 1.777875 0.04845168

DGCR2 DiGeorge syndrome critical region gene 2 1.777194 0.03677183 1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P

Symbol Change value

PPP2R5A protein phosphatase 2, regulatory subunit B', alpha 1.776972 0.03961713

U C84A Unc-84 homolog A (C. elegans) 1.776587 0.04309932

RTN4 Reticulon 4 1.776363 0.01948926

MIPOL1 mirror-image Polydactyly 1 1.77569 0.03332746

XRCC3 X-ray repair complementing defective repair in 1.775659 0.04521804

Chinese hamster cells 3

ELL elongation factor RNA polymerase II 1.775647 0.02696673

Clorfl l4 #N/A 1.775577 0.04898113

C7orf54 #N/A 1.775088 0.03773488

FGGY FGGY carbohydrate kinase domain containing 1.774808 0.02179662

LVR #N/A 1.774804 0.00064064

KRT6A keratin 6A 1.774477 0.01592729

ATAD3A ATPase family, AAA domain containing 3A 1.774155 0.01641257

CAPN9 calpain 9 1.773901 0.00709331

SRGAP1 SLIT-ROBO Rho GTPase activating protein 1 1.77357 0.01567887

SEC23A Sec23 homolog A (S. cerevisiae) 1.772801 0.02654777

SOX13 SRY (sex determining region Y)-box 13 1.772618 0.04520642

MSL3 male-specific lethal 3 homolog (Drosophila) 1.772485 0.03587881

GBA glucosidase, beta, acid 1.772456 0.02752661

SMG1 SMG1 homolog, phosphatidylinositol 3-kinase- 1.771998 0.01037175 related kinase (C. elegans)

PLCB1 phospholipase C, beta 1 (phosphoinositide- 1.771847 0.03330809 specific)

NCF1 neutrophil cytosolic factor 1 1.771446 0.00609771

NCAPH2 non-SMC condensin II complex, subunit H2 1.771348 0.00192561

LRCH3 leucine-rich repeats and calponin homology (CH) 1.771288 0.02829728 domain containing 3

BPNT1 #N/A 1.771126 0.0442052

MPP7 membrane protein, palmitoylated 7 (M AGU p55 1.770808 0.03390227 subfamily member 7)

SLC24A1 solute carrier family 24 1.770405 0.01181665

(sodium/potassium/calcium exchanger), member 1

COL19A1 collagen, type XIX, alpha 1 1.769544 0.00758784

CTA- Hypothetical FLJ23584 1.769128 7.63E-06

216E10.6

MGLL monoglyceride lipase 1.769073 0.01765371

DUSP23 dual specificity phosphatase 23 1.769028 0.02176854

DCP1B DCP1 decapping enzyme homolog B (S. 1.768896 0.04886241 cerevisiae)

LDB1 LIM domain binding 1 1.768377 0.04418318

TNFRSF2 tumor necrosis factor receptor superfamily, 1.768189 0.0455518

1 member 21

RPS6KC1 ribosomal protein S6 kinase, 52kDa, polypeptide 1 1.767957 0.01187031

TARBP1 TAR (HIV-1) RNA binding protein 1 1.76731 0.04997674

JOSD1 Josephin domain containing 1 1.766767 0.04966897

BCAR3 breast cancer anti-estrogen resistance 3 1.766686 0.04741963

UBL4A #N/A 1.766604 0.01994057

KRT28 keratin 28 1.766388 0.0200145

MUC1 #N/A 1.766316 0.04988542

DNAJC16 DnaJ (Hsp40) homolog, subfamily C, member 16 1.765974 0.00128657

DB l/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P Symbol Change value

ACOl aconitase 1, soluble 1.765545 0.02519563

CCT6B chaperonin containing TCPl, subunit 6B (zeta 2) 1.765154 0.01441639

ZNF234 zinc finger protein 234 1.764221 0.04129703

WEE1 WEE1 homolog (S. pombe) 1.76422 0.0190755

UGT3A2 UDP glycosyltransferase 3 family, polypeptide A2 1.763886 0.00745899

TKTL2 #N/A 1.763472 0.00224344

GBA2 glucosidase, beta (bile acid) 2 1.76299 0.00583495

MLL5 myeloid/lymphoid or mixed-lineage leukemia 5 1.762872 0.03968122

(trithorax homolog, Drosophila)

RBM24 RNA binding motif protein 24 1.762854 0.00083583

ALK anaplastic lymphoma receptor tyrosine kinase 1.762772 0.02290011

AFTPH aftiphilin 1.762753 0.03581729

FGD2 FYVE, RhoGEF and PH domain containing 2 1.762355 0.0043171 1

RETN resistin 1.762318 0.01546848

RBKS ribokinase 1.76176 0.04351475

ZFHX4 zinc finger homeobox 4 1.761664 0.02954824

CBLC Cas-Br-M (murine) ecotropic retroviral 1.761662 0.010678 transforming sequence c

USHBP1 Usher syndrome 1C binding protein 1 1.761661 0.02372015

MTHFD2 methylenetetrahydrofolate dehydrogenase 1.761655 0.03894478

L ( ADP+ dependent) 2-like

KLF4 Kruppel-like factor 4 (gut) 1.761564 0.01640878

BCL6 #N/A 1.76123 0.0286744

NUDCD3 NudC domain containing 3 1.760927 0.0474457

KIAA201 #N/A 1.760852 0.02436456

3

RTN3 reticulon 3 1.760713 0.021 11797

SH2D3C SH2 domain containing 3C 1.760554 0.00272672

USP39 ubiquitin specific peptidase 39 1.760536 0.03374848

GOLGB1 golgin Bl 1.760309 0.0356427

GPR155 G protein-coupled receptor 155 1.759774 0.01942222

LENG8 Leukocyte receptor cluster (LRC) member 8 1.758963 0.0175276

RICH2 Rho-type GTPase-activating protein RICH2 1.758936 0.04179542

PAPSS1 3'-phosphoadenosine 5'-phosphosulfate synthase 1 1.758882 0.04546671

BMPR2 bone morphogenetic protein receptor, type II 1.758291 0.04976859

(serine/threonine kinase)

KIF26B #N/A 1.758279 0.03171182

MAP3K7I Mitogen-activated protein kinase kinase kinase 7 1.758279 0.02067163

P3 interacting protein 3

MLL4 myeloid/lymphoid or mixed-lineage leukemia 4 1.758142 0.00894005

ZNF225 zinc finger protein 225 1.757809 0.03519834

MBNL3 #N/A 1.757298 0.01480562

RAI14 retinoic acid induced 14 1.75729 0.03349575

ATF3 activating transcription factor 3 1.756661 0.0451451

FBX039 #N/A 1.756165 0.00121815

UBQLN4 ubiquilin 4 1.7561 14 0.02382911

FAM105A family with sequence similarity 105, member A 1.756019 0.02698624

B4GALN beta-l,4-N-acetyl-galactosaminyl transferase 3 1.755953 0.02418084

T3

ADAMTS ADAM metallopeptidase with thrombospondin 1.75562 0.04203138

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

19 type 1 motif, 19

LOC4402 similar to p40 1.755187 0.01646372 58

ZNF184 zinc finger protein 184 1.754955 0.02223986 ZNF445 zinc finger protein 445 1.754923 0.03286542 LRWD1 leucine-rich repeats and WD repeat domain 1.754383 0.01448462 containing 1

G6PD glucose-6-phosphate dehydrogenase 1.753382 0.02781807

TOPBP1 topoisomerase (DNA) II binding protein 1 1.753342 0.04355243

MAGEA5 melanoma antigen family A, 5 1.753252 0.02734386

Clorfl4 chromosome 1 open reading frame 14 1.753243 0.03546329

GSTA4 glutathione S-transferase alpha 4 1.753107 0.00541283

PLXNA3 Plexin A3 1.752528 0.0007546

C3orf52 #N/A 1.752221 0.02216849

SCN5A sodium channel, voltage-gated, type V, alpha 1.752179 0.02554011 subunit

C22orf9 #N/A 1.752071 0.04045017 SEC14L1 SEC14-like 1 (S. cerevisiae) 1.751624 0.0065086 CACNA2 calcium channel, voltage-dependent, alpha 2/delta 1.749697 0.01832449 D3 subunit 3

EIF3D eukaryotic translation initiation factor 3, subunit D 1.749589 0.03090098 DGAT1 diacylglycerol O-acyltransferase homolog 1 1.749071 0.03456439

(mouse)

COX4I1 #N/A 1.749039 0.03773461 EVI5 ecotropic viral integration site 5 1.748676 0.01688849 TGFA transforming growth factor, alpha 1.748632 0.03193993 SEMA6A Sema domain, transmembrane domain (TM), and 1.748458 0.01669209 cytoplasmic domain, (semaphorin) 6A

ZNF410 zinc finger protein 410 1.748024 0.01204823 NHLH1 #N/A 1.747231 0.03028152 COBLL1 COBL-like 1 1.747195 0.04850633 SLC23A2 solute carrier family 23 (nucleobase transporters), 1.747049 0.04342467 member 2

NPHP4 nephronophthisis 4 1.746754 0.03738345

CSRP2BP CSRP2 binding protein 1.746524 0.02273079

GAB1 GRB2-associated binding protein 1 1.746467 0.03029872

C20orfl32 chromosome 20 open reading frame 132 1.746253 0.035852

DOC2A double C2-like domains, alpha 1.74612 0.02490822

GTPBP2 #N/A 1.745407 0.02223491

ERF #N/A 1.74482 0.02510774

TNKS tankyrase, TRF1 -interacting ankyrin-related ADP- 1.744666 0.04627214 ribose polymerase

SEC24D SEC24 family, member D (S. cerevisiae) 1.744358 0.03911211

8-Sep #N/A 1.744145 0.00582905 GMIP GEM interacting protein 1.744115 0.03051105 EPHA3 EPH receptor A3 1.7441 1 0.02174902 PCDHGB protocadherin gamma subfamily B, 1 1.743643 0.03759205 1

STAT1 signal transducer and activator of transcription 1, 1.74348 0.04240031

91kDa

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

UNC50 unc-50 homolog (C. elegans) 1.743399 0.04456063

MY015A myosin XVA 1.742508 0.03231288

TDRD3 tudor domain containing 3 1.742328 0.04813857

TRIP 13 thyroid hormone receptor interactor 13 1.741503 0.03023358

PI FYVE phosphoinositide kinase, FYVE finger containing 1.741298 0.0125666

TMEM19 transmembrane protein 192 1.741076 0.02259603

2

AGFG1 ArfGAP with FG repeats 1 1.740148 0.00038148 IGFL4 #N/A 1.73996 0.03696647 RAB24 RAB24, member RAS oncogene family 1.739907 0.01928266 NDUFB11 NADH dehydrogenase (ubiquinone) 1 beta 1.73983 0.02005851 subcomplex, 1 1, 17.3kDa

MAB21L1 #N/A 1.739804 0.03588803 NKRF NFKB repressing factor 1.739686 0.04900439 Cl lorf74 #N/A 1.739683 0.02350089 NDUFS1 NADH dehydrogenase (ubiquinone) Fe-S protein 1.739642 0.021 14725

1, 75kDa (NADH-coenzyme Q reductase)

POU2F1 POU class 2 homeobox 1 1.739423 0.02085693 FAP2 microfibrillar-associated protein 2 1.739182 0.03267798

SEC22C SEC22 vesicle trafficking protein homolog C (S. 1.739063 0.00442219 cerevisiae)

ADAM2 ADAM metallopeptidase domain 2 1.738719 0.03982981 MTMR1 myotubularin related protein 1 1.738523 0.01841331 DR1 down-regulator of transcription 1, TBP-binding 1.738386 0.04902791

(negative cofactor 2)

EIF2C2 eukaryotic translation initiation factor 2C, 2 1.737381 0.02796271 DUSP3 dual specificity phosphatase 3 1.737377 0.00223923 ABCA2 ATP-binding cassette, sub-family A (ABC1), 1.736876 0.01473507 member 2

STK11IP serine/threonine kinase 11 interacting protein 1.736757 0.02103678

RAB3D RAB3D, member RAS oncogene family 1.736335 0.0302014

CADM4 #N/A 1.73612 0.03829267

CDK5RA CDK5 regulatory subunit associated protein 2 1.735693 0.02311894

P2

COPS5 COP9 constitutive photomorphogenic homolog 1.73531 0.01165778 subunit 5 (Arabidopsis)

TSC2 tuberous sclerosis 2 1.735243 0.04697442

PAX6 paired box 6 1.735007 5.01E-06

NVL nuclear VCP-like 1.734827 0.00569968

C19orf44 chromosome 19 open reading frame 44 1.734504 0.04317116

TTC39B tetratricopeptide repeat domain 39B 1.734211 0.04698457

TRAPPC1 #N/A 1.733987 0.02811378

0

DCHS2 dachsous 2 (Drosophila) 1.733625 0.03898632

ZBTB2 zinc finger and BTB domain containing 2 1.733558 0.02724021

LCA5 Leber congenital amaurosis 5 1.733514 0.01777422

FBXL17 F-box and leucine-rich repeat protein 17 1.733476 0.02285153

SFXN5 sideroflexin 5 1.733428 0.00361959

PEX26 peroxisomal biogenesis factor 26 1.733322 6.10E-05

RAB3IP RAB3A interacting protein (rabin3) 1.73291 0.03062512 1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

BCL9 B-cell CLL/lymphoma 9 1.732645 0.01182714

SORD sorbitol dehydrogenase 1.732637 0.00609886

KDM5B lysine (K)-specific demethylase 5B 1.732628 0.04388569

MFSD3 major facilitator superfamily domain containing 3 1.732624 0.00186089

LRRC1 Leucine rich repeat containing 1 1.732577 0.01498779

G6PC2 #N/A 1.732403 0.02479933

TRAM2 translocation associated membrane protein 2 1.731537 0.0246794

PTK2 PT 2 protein tyrosine kinase 2 1.731098 0.03442737

RRP12 ribosomal RNA processing 12 homolog (S. 1.730868 0.01376982 cerevisiae)

PPARG peroxisome proliferator-activated receptor gamma 1.730854 0.02459021

KLC2 Kinesin light chain 2 1.730599 0.03664663

SLC19A1 solute carrier family 19 (folate transporter), 1.730571 0.01485065 member 1

LPCAT3 lysophosphatidylcholine acyltransferase 3 1.729979 0.04133057

ARHGEF Rho guanine nucleotide exchange factor (GEF) 3 1.729836 0.04145086

3

ACACA acetyl-CoA carboxylase alpha 1.729759 0.04237568 NUP210 nucleoporin 21 OkDa 1.729416 0.04084509 ANKMY1 ankyrin repeat and MYND domain containing 1 1.729163 0.0270179 OGT O-linked N-acetylglucosamine (GlcNAc) 1.728718 0.04340233 transferase (UDP-N- acetylglucosamine:polypeptide-N- acetylglucosaminyl transferase)

S100A9 #N/A 1.728669 0.00818468 RBM22 RNA binding motif protein 22 1.728626 0.01614761 ITSN2 intersectin 2 1.726993 0.04145017 OS9 osteosarcoma amplified 9, endoplasmic reticulum 1.725916 0.01749409 lectin

FAM38A family with sequence similarity 38, member A 1.72533 0.0335846 PIK3R1 phosphoinositide-3 -kinase, regulatory subunit 1 1.724967 0.04257376

(alpha)

PCCA propionyl CoA carboxylase, alpha polypeptide 1.724233 0.01410244

DOCK9 dedicator of cytokinesis 9 1.724079 0.02135059

GABRG3 gamma-aminobutyric acid (GABA) A receptor, 1.724029 0.03300689 gamma 3

DEFA5 defensin, alpha 5, Paneth cell-specific 1.723663 0.00578865

NOTCH3 Notch homolog 3 (Drosophila) 1.723621 0.03672981

CPEB2 cytoplasmic polyadenylation element binding 1.723351 0.00139721 protein 2

HECTD1 HECT domain containing 1 1.723184 0.04818697 PLXNC1 plexin CI 1.723158 0.01013153 ABCA4 ATP-binding cassette, sub-family A (ABC1), 1.722941 0.04232054 member 4

DCC #N/A 1.722929 0.00956524

LAMC1 laminin, gamma 1 (formerly LAMB2) 1.722821 0.02734652

OPN3 opsin 3 1.722424 0.03608216

KATNAL #N/A 1.722216 0.01175097

1

HOXC8 homeobox C8 1.721862 0.04974292 1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P

Symbol Change value

NFXL1 Nuclear transcription factor, X-box binding-like 1 1.721555 0.02761823

PORCN porcupine homolog (Drosophila) 1.721067 0.04807794

APTX Aprataxin 1.720781 0.04496039

PLEKHM pleckstrin homology domain containing, family M 1.720765 0.04294087

2 (with RUN domain) member 2

MYO10 myosin X 1.72049 0.03749112

GRK6 G protein-coupled receptor kinase 6 1.71984 0.03663987

SSH2 slingshot homolog 2 (Drosophila) 1.719656 0.03325557

VAMP4 vesicle-associated membrane protein 4 1.719461 0.02416613

CRISPLD cysteine-rich secretory protein LCCL domain 1.719216 0.01 156081

2 containing 2

ANXAl annexin Al 1.719177 0.04489786 DMC1 DMC1 dosage suppressor of mckt homolog, 1.719172 0.00216327 meiosis-specific homologous recombination

(yeast)

NCOA2 nuclear receptor coactivator 2 1.71912 0.01425815 DUSP22 dual specificity phosphatase 22 1.718997 0.02891459 PRCC papillary renal cell carcinoma (translocation- 1.718941 0.04542483 associated)

COL4A5 collagen, type IV, alpha 5 1.718934 0.03131216 LONRF2 LON peptidase N-terminal domain and ring finger 1.718819 0.01 141586

2

COX4I2 #N/A 1.718641 0.03059842 SLC9A2 solute carrier family 9 (sodium/hydrogen 1.718166 0.02822742 exchanger), member 2

EXOG endo/exonuclease (5 '-3'), endonuclease G-Iike 1.717836 0.02194731

C12orf60 #N/A 1.71779 0.0298019

C5orf30 chromosome 5 open reading frame 30 1.717496 0.033414

COL21A1 collagen, type XXI, alpha 1 1.717491 0.00862176

HAS 3 #N/A 1.717446 0.04575845

BAI1 brain-specific angiogenesis inhibitor 1 1.717373 0.00815145

RERE arginine-glutamic acid dipeptide (RE) repeats 1.71735 0.0138092

WHSC1 Wolf-Hirschhorn syndrome candidate 1 1.717052 0.03095402

HERC2 hect domain and RLD 2 1.717048 0.03923331

PCSK6 proprotein convertase subtilisin/kexin type 6 1.716871 0.03369358

CEP97 centrosomal protein 97kDa 1.716708 0.01188736

MRPL55 Mitochondrial ribosomal protein L55 1.71648 0.03894057

HARS2 histidyl-tRNA synthetase 2, mitochondrial 1.715719 0.03591061

(putative)

SLC35B2 solute carrier family 35, member B2 1.715575 0.03768911 KIAA130 Raptor 1.715481 0.01002851 3

DNAJB5 DnaJ (Hsp40) homolog, subfamily B, member 5 1.71473 0.02289742 CCDC91 coiled-coil domain containing 91 1.71455 0.00648879 DE ND5 DENN/MADD domain containing 5B 1.714332 0.02185475 B

PSMD14 proteasome (prosome, macropain) 26S subunit, 1.713989 0.02500735 non-ATPase, 14

IRF6 interferon regulatory factor 6 1.713118 0.0205667 GPATCH G patch domain containing 1 1.712933 0.04344977

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

1

AJAP1 adherens junctions associated protein 1 1.712712 0.01253223

PCNXL2 Pecanex-like 2 (Drosophila) 1.712481 0.04600786

MAP4K4 mitogen-activated protein kinase kinase kinase 1.712186 0.04245277 kinase 4

TOX2 TOX high mobility group box family member 2 1.712142 0.01986638

CDK5 #N/A 1.712097 0.04453054

GPRC5C #N/A 1.71 1964 0.01376975

B9D2 #N/A 1.711881 0.03348781

RPS6KA1 ribosomal protein S6 kinase, 90kDa, polypeptide 1 1.711861 0.02549594

MYH6 myosin, heavy chain 6, cardiac muscle, alpha 1.711724 0.01693347

CETP #N/A 1.710863 0.01956263

ATP8B1 ATPase, aminophospholipid transporter, class I, 1.710738 0.02400154 type 8B, member 1

COQ7 coenzyme Q7 homolog, ubiquinone (yeast) 1.710519 0.02874881

ZNF202 #N/A 1.71042 0.01387536

MAP4K3 mitogen-activated protein kinase kinase kinase 1.710348 0.0179431 1 kinase 3

TPRG1L tumor protein p63 regulated 1 -like 1.709752 0.02459877

FBXL2 F-box and leucine-rich repeat protein 2 1.70972 0.04192718

SI sucrase-isomaltase (alpha-glucosidase) 1.709514 0.04940818

GRIN1 #N/A 1.709203 0.04015842

MY019 #N/A 1.709143 0.022694

SPOCD1 SPOC domain containing 1 1.709134 0.04237795

LPIN2 lipin 2 1.708429 0.00705372

MED 8 mediator complex subunit 8 1.708003 0.00678397

AP2A2 adaptor-related protein complex 2, alpha 2 subunit 1.707895 0.01275162

ADAMTS ADAMTS -like 4 1.70756 0.00646457

L4

HCFC1 host cell factor CI (VP16-accessory protein) 1.707475 0.0240554 GALNT7 UDP-N-acetyl-alpha-D-galactosamine:polypeptide 1.707402 0.01737331

N-acetylgalactosaminyltransferase 7 (GalNAc-T7)

FNIP1 Folliculin interacting protein 1 1.707247 0.04196063

YTHDC2 YTH domain containing 2 1.707026 0.03883546

GRHL2 grainyhead-like 2 (Drosophila) 1.706873 0.02848341

GGCX gamma-glutamyl carboxylase 1.706652 0.04784631

SLC05A1 #N/A 1.706296 0.0130894

HIST1H3 #N/A 1.706099 0.02187137

H

POMT1 protein-O-mannosyltransferase 1 1.705442 0.03660587

SYT12 synaptotagmin XII 1.705407 0.04558376

FLJ41423 hypothetical LOC399886 1.705362 0.02232278

PD1A5 protein disulfide isomerase family A, member 5 1.705199 0.02030493

KIF1C kinesin family member 1 C 1.704965 0.02851004

UGDH UDP-glucose 6-dehydrogenase 1.704915 0.02264137

RNPEP arginyl aminopeptidase (aminopeptidase B) 1.704725 0.0130882

YEATS2 YEATS domain containing 2 1.704584 0.03356943

SLC43A1 solute carrier family 43, member 1 1.704326 0.01980745

ZNF491 #N/A 1.704156 0.04566768

SUPT3H suppressor of Ty 3 homolog (S. cerevisiae) 1.703882 0.04472675

DB l/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

CNKSR2 connector enhancer of kinase suppressor of Ras 2 1.703803 0.00125035

TMED8 #N/A 1.703346 0.04469418

ACPI acid phosphatase 1, soluble 1.702812 0.01354428

PNPLA7 patatin-like phospholipase domain containing 7 1.702054 0.01823767

SPATA5 Spermatogenesis associated 5 1.701947 0.02535752

PPM1J protein phosphatase, Mg2+/Mn2+ dependent, 1 J 1.70186 0.00359878

TNFRSF1 #N/A 1.701542 0.01456482 7

ITPR2 inositol 1,4,5-triphosphate receptor, type 2 1.701366 0.04825517

FXYD5 FXYD domain containing ion transport regulator 5 1.701181 0.0201854

C6orf48 chromosome 6 open reading frame 48 1.70108 0.00120355

PSD4 pleckstrin and Sec7 domain containing 4 1.700869 0.04786245

RGS22 regulator ofG-protein signaling 22 1.700765 0.04004377

TRPC1 transient receptor potential cation channel, 1.700626 0.01678772 subfamily C, member 1

UBE2Q2 ubiquitin-conjugating enzyme E2Q family 1.700414 0.04847906 member 2

SGIP1 SH3-domain GRB2-like (endophilin) interacting 1.69988 0.02289891 protein 1

KBTBD11 kelch repeat and BTB (POZ) domain containing 1.699722 0.03785156

11

USP37 ubiquitin specific peptidase 37 1.699715 0.02291508

TMEM79 transmembrane protein 79 1.699667 0.01475681

MCC mutated in colorectal cancers 1.699002 0.01025102

LARGE like-glycosyltransferase 1.698708 0.03318614

ICA1 islet cell autoantigen 1 , 69kDa 1.698273 0.02068454

VPS4B vacuolar protein sorting 4 homolog B (S. 1.698022 0.02540869 cerevisiae)

LARS2 leucyl-tRNA synthetase 2, mitochondrial 1.697436 0.04425727

CELSR2 cadherin, EGF LAG seven-pass G-type receptor 2 1.69742 0.00621362

(flamingo homolog, Drosophila)

C4orf37 chromosome 4 open reading frame 37 1.697284 0.01673239

PLEKHG pleckstrin homology domain containing, family G 1.696324 0.02681379 7 (with RhoGef domain) member 7

BACH1 BTB and CNC homology 1, basic leucine zipper 1.696301 0.02582705 transcription factor 1

NINL ninein-like 1.696298 0.02549016

SMARCC SWI/SNF related, matrix associated, actin 1.695632 0.03476895 2 dependent regulator of chromatin, subfamily c,

member 2

NSUN2 NOP2/Sun domain family, member 2 1.695474 0.04200569

CREB3L4 cAMP responsive element binding protein 3-like 4 1.695449 0.0157779

UBFD1 ubiquitin family domain containing 1 1.695431 0.03678202

ZNF710 zinc finger protein 710 1.695233 0.03756483

PTGIS #N/A 1.694779 0.04036578

PTDSS1 phosphatidylserine synthase 1 1.694561 0.01229464

TMED4 transmembrane emp24 protein transport domain 1.694517 0.0165239 containing 4

DLG5 discs, large homolog 5 (Drosophila) 1.694485 0.03756438

RU DC2 #N/A 1.693796 0.04140832

DB l/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

A

LRIG1 leucine-rich repeats and immunoglobulin-like 1.692463 0.01701531 domains 1

RETSAT retinol saturase (all-trans-retinol 13,14-reductase) 1.692359 0.0411033

PCNT pericentrin 1.692233 0.01662058

ITGAE integrin, alpha E (antigen CD 103, human mucosal 1.692199 0.01863436 lymphocyte antigen 1 ; alpha polypeptide)

CYLD cylindromatosis (turban tumor syndrome) 1.691563 0.01414714

CCDC113 coiled-coil domain containing 1 13 1.69136 0.03077135

DSTYK dual serine/threonine and tyrosine protein kinase 1.691355 0.00539049

CSMD3 CUB and Sushi multiple domains 3 1.691102 0.02490313

BLVRA biliverdin reductase A 1.690993 0.01560663

DNASE1 deoxyribonuclease I 1.690872 0.04928682

DCTPP1 #N/A 1.690487 0.00930683

FANCD2 Fanconi anemia, complementation group D2 1.69041 0.04011305

MAN2B2 mannosidase, alpha, class 2B, member 2 1.690398 0.00707656

POLQ polymerase (DNA directed), theta 1.689642 0.03466341

CYP7B1 #N/A 1.689456 0.0346976

EDARAD EDAR-associated death domain 1.689192 0.00677352

D

CPOX coproporphyrinogen oxidase 1.689126 0.04043278

RIFl RAP1 interacting factor homolog (yeast) 1.688849 0.0479608

PRR20 #N/A 1.688646 0.00649377

FHDC1 FH2 domain containing 1 1.688589 0.00499825

GARNL4 GTPase activating Rap/RanGAP domain-like 4 1.688231 0.01702185

SLBP stem-loop binding protein 1.688073 0.00199265

EIF4A2 eukaryotic translation initiation factor 4A2 1.687964 0.03002884

C20orfl l2 chromosome 20 open reading frame 112 1.686882 0.01093454

TNP02 transportin 2 1.686825 0.01774808

WDR46 WD repeat domain 46 1.686755 0.00305649

BIN 2 bridging integrator 2 1.686613 0.04131404

ADAP2 ArfGAP with dual PH domains 2 1.686238 0.02583013

REG1P regenerating islet-derived 1 pseudogene 1.68621 0.02090773

ZNF302 zinc finger protein 302 1.686208 0.03888947

DOPEY2 dopey family member 2 1.686028 0.02777988

DNAJB12 DnaJ (Hsp40) homolog, subfamily B, member 12 1.685901 0.02182576

TMEM16 transmembrane protein 167B 1.684935 0.03744605

7B

B4GALT4 UDP-Gal:betaGlcNAc beta 1,4- 1.684828 0.04699694 galactosyltransferase, polypeptide 4

SEC31A SEC31 homolog A (S. cerevisiae) 1.684689 0.03088132

NR5A2 nuclear receptor subfamily 5, group A, member 2 1.684315 0.02466303

POLG2 polymerase (DNA directed), gamma 2, accessory 1.683536 0.00878715 subunit

TUSC5 tumor suppressor candidate 5 1.683376 0.03123336

IDH3A isocitrate dehydrogenase 3 (NAD+) alpha 1.683264 0.04905133

HNRNPL heterogeneous nuclear ribonucleoprotein L 1.683002 0.03736026

AN 3 ankyrin 3, node of Ranvier (ankyrin G) 1.682996 0.00341445

SLC12A4 solute carrier family 12 (potassium/chloride 1.682615 0.00691218 transporters), member 4

DB l/ 69437510.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

PVRL1 poliovirus receptor-related 1 (herpesvirus entry 1.682399 0.00467766 mediator C)

REPS1 RALBP1 associated Eps domain containing 1 1.682031 0.03344135

LAMA2 laminin, alpha 2 1.6818 0.04749907

BRF1 BRF1 homolog, subunit of RNA polymerase III 1.681429 0.0193653 transcription initiation factor IIIB (S. cerevisiae)

KCNC2 potassium voltage-gated channel, Shaw-related 1.681412 0.02312417 subfamily, member 2

PYGM phosphorylase, glycogen, muscle 1.681322 0.03291234

DHX38 DEAH (Asp-Glu-Ala-His) box polypeptide 38 1.681181 0.04157917

DDIT4L DNA-damage-inducible transcript 4-like 1.680862 0.02337816

BCMOl beta-carotene 15,15'-monooxygenase 1 1.680631 0.00020663

MPRIP myosin phosphatase Rho interacting protein 1.6798 0.01460054

ITGB3 integrin, beta 3 (platelet glycoprotein Ilia, antigen 1.679276 0.00090458

CD61)

GRSF1 G-rich RNA sequence binding factor 1 1.67919 0.0373075

LRP5 Low density lipoprotein receptor-related protein 5 1.678925 0.04639084

P4HA3 prolyl 4-hydroxylase, alpha polypeptide III 1.678915 0.0309688

PARP12 poly (ADP-ribose) polymerase family, member 12 1.678731 0.00841189

SLC6A3 solute carrier family 6 (neurotransmitter 1.678629 0.04572979 transporter, dopamine), member 3

MYOM3 myomesin family, member 3 1.678119 0.03670593

HIBADH 3 -hy droxyisobutyrate dehydro genase 1.67803 0.02993685

LAMB3 laminin, beta 3 1.677836 0.03071771

HMGXB4 HMG box domain containing 4 1.677641 0.02509293

C5orf42 chromosome 5 open reading frame 42 1.67753 0.03526079

KIR2DL4 killer cell immunoglobulin-like receptor, two 1.677121 0.01026487 domains, long cytoplasmic tail, 4

OBSCN obscurin, cytoskeletal calmodulin and titin- 1.676873 0.02544353 interacting RhoGEF

LTBP2 latent transforming growth factor beta binding 1.676579 0.03036016 protein 2

MKRN3 makorin ring finger protein 3 1.676295 0.01039506

MGC4580 #N/A 1.676225 0.03605379

0

PDZD2 PDZ domain containing 2 1.676118 0.02083215 DUS2L dihydrouridine synthase 2-like, SMM1 homolog 1.675614 0.03293131

(S. cerevisiae)

P2RX1 purinergic receptor P2X, ligand-gated ion channel, 1.675548 0.0278964

1

LBR #N/A 1.675495 0.04944818 BAZ1B bromodomain adj cent to zinc finger domain, IB 1.675443 0.006049 LRRC37A leucine rich repeat containing 37, member A2 1.67535 0.02758695 2

CDK9 #N/A 1.675113 0.04960095 GSTZ1 glutathione transferase zeta 1 1.674763 0.00927053 MAD 1 LI MAD1 mitotic arrest deficient-like 1 (yeast) 1.674637 0.02094092 CABIN 1 calcineurin binding protein 1 1.674503 0.00141662 TICAM2 toll-like receptor adaptor molecule 2 1.674473 0.02729191 GOLGA3 golgin A3 1.674292 0.04549478

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P

Symbol Change value

FLNB filamin B, beta 1.674149 0.00227185

PCDH15 Protocadherin 15 1.673851 0.0381 1484

PTPN13 protein tyrosine phosphatase, non-receptor type 13 1.673794 0.0149167

(APO-1/CD95 (Fas)-associated phosphatase)

SLC12A5 solute earner family 12 (potassium/chloride 1.673592 0.02038864 transporter), member 5

VPS39 vacuolar protein sorting 39 homolog (S. 1.673251 0.01561087 cerevisiae)

OR10G7 Olfactory receptor, family 10, subfamily G, 1.672903 0.00347311 member 7

SLC25A1 solute carrier family 25 (mitochondrial carrier, 1.672861 0.04304577 4 brain), member 14

MGAM maltase-glucoamylase (alpha-glucosidase) 1.672786 0.01935983

TTC17 tetratricopeptide repeat domain 17 1.672722 0.02732361

PTN pleiotrophin 1.672444 0.00274229

SURF2 #N/A 1.671991 0.04659518

IMMT inner membrane protein, mitochondrial 1.671288 0.00538103

MORF4L mortality factor 4 like 2 1.670879 0.00982228

2

ARHGAP Rho GTPase activating protein 30 1.670872 0.03033886 30

AADACL #N/A 1.670771 0.00609074 1

ZSWIM3 #N/A 1.67077 0.02358262

BAIAP2L BAI1 -associated protein 2-like 1 1.670402 0.02269513

1

AKAP12 A kinase (PRKA) anchor protein 12 1.670086 0.00481882

KHDRBS KH domain containing, RNA binding, signal 1.670006 0.01783706

2 transduction associated 2

SYNGR2 synaptogyrin 2 1.669943 0.00082102

C7orf70 chromosome 7 open reading frame 70 1.669605 0.0044761

TBCKL #N/A 1.669505 0.01902436

SGCE sarcoglycan, epsilon 1.669432 0.0239744

RAPH1 Ras association (RalGDS/AF-6) and pieckstrin 1.669251 0.01958833 homology domains 1

TRMT5 TRM5 tRNA methyltransferase 5 homolog (S. 1.668629 0.02094255 cerevisiae)

IKZF5 #N/A 1.668327 0.01 163852

SDR39U1 #N/A 1.668294 0.02074351

UBL7 ubiquitin-like 7 (bone marrow stromal cell- 1.668008 0.03185661 derived)

CD33 CD33 molecule 1.66771 1 0.01845913

DCDC2 doublecortin domain containing 2 1.667659 0.01155908

ZFAT zinc finger and AT hook domain containing 1.667636 0.03825848

TMC1 transmembrane channel-like 1 1.667431 0.01316726

FER fer (fps/fes related) tyrosine kinase 1.667235 0.01911994

TLR4 toll-like receptor 4 1.666932 0.02679148

CCDC22 coiled-coil domain containing 22 1.666931 0.02143564

PPP1R15 #N/A 1.666918 0.00530079

A

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P

Symbol Change value

MYB v-myb myeloblastosis viral oncogene homolog 1.666903 0.03996438

(avian)

HSD17B7 hydroxysteroid (17-beta) dehydrogenase 7 1.666809 0.02995118

SELL selectin L 1.666633 0.02162888

GPR151 #N/A 1.666506 0.00992773

MAP4K2 mitogen-activated protein kinase kinase kinase 1.666455 0.03099083 kinase 2

FGD3 FYVE, RhoGEF and PH domain containing 3 1.666356 0.01460297

PCDHB11 #N/A 1.666195 0.03077624

LYST lysosomal trafficking regulator 1.666014 0.03110142

OSBPL3 #N/A 1.666006 0.00703659

RHOT2 ras homolog gene family, member T2 1.66596 0.04459323

C12orf4 Chromosome 12 open reading frame 4 1.665847 0.04287477

SPEF1 sperm flagellar 1 1.665351 0.02507237

ETFA electron-transfer-flavoprotein, alpha polypeptide 1.665195 0.02149139

OLIG1 oligodendrocyte transcription factor 1 1.665143 0.00716005

NLRX1 NLR family member XI 1.665095 0.03340494

PDCD2 programmed cell death 2 1.664955 0.02292029

CHN2 chimerin (chimaerin) 2 1.66453 0.0487137

THADA thyroid adenoma associated 1.664419 0.03990602

GLT25D2 glycosyltransferase 25 domain containing 2 1.66425 0.03389155

SCAMP4 #N/A 1.664201 0.02354862

IDH1 isocitrate dehydrogenase 1 (NADP+), soluble 1.664042 0.02657377

MAOA monoamine oxidase A 1.663427 0.04092647

SYNE1 spectrin repeat containing, nuclear envelope 1 1.663154 0.046808

STAMBP STAM binding protein 1.663149 0.00820563

BRDT bromodomain, testis-specific 1.662949 0.04162642

STAG3L1 stromal antigen 3 -like 1 1.662675 0.02648026

ZNF45 zinc finger protein 45 1.662617 0.02932117

PTCH1 patched homolog 1 (Drosophila) 1.662359 0.01379689

EMB embigin homolog (mouse) 1.661962 0.03133711

ZDHHC4 zinc finger, DHHC-type containing 4 1.66193 0.04152488

AHCYL2 adenosylhomocysteinase-like 2 1.661859 0.02320016

DNAH9 dynein, axonemal, heavy chain 9 1.661616 0.044718

KIF15 kinesin family member 15 1.661378 0.04729327

PPP4R1 protein phosphatase 4, regulatory subunit 1 1.661341 0.02453422

C17orf85 chromosome 17 open reading frame 85 1.660959 0.03169091

SMG7 Smg-7 homolog, nonsense mediated mRNA decay 1.660735 0.03318053 factor (C. elegans)

SLC15A4 solute carrier family 15, member 4 1.660637 0.0335626

ROPN1L ropporin 1 -like 1.660604 0.04463225

POU2F3 POU class 2 homeobox 3 1.660559 0.00944756

IGF2R insulin-like growth factor 2 receptor 1.66019 0.03101422

BBS4 Bardet-Biedl syndrome 4 1.659758 0.02639537

OR13H1 #N/A 1.659414 0.00175343

PSMD2 proteasome (prosome, macropain) 26S subunit, 1.659115 0.01979753 non-ATPase, 2

TCEAL8 #N/A 1.65911 0.0160528

PBRM1 polybromo 1 1.659059 0.00602285

PLEK2 #N/A 1.65905 0.00937674

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregu ated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

ODZ1 odz, odd Oz/ten-m homolog 1 (Drosophila) 1.658837 0.03902684

ZYG11A zyg-11 homolog A (C. elegans) 1.658804 0.03693494

SLC7A7 solute carrier family 7 (cationic amino acid 1.658712 0.02160492 transporter, y+ system), member 7

ZXDC ZXD family zinc finger C 1.65836 0.03600102

FGD6 FYVE, RhoGEF and PH domain containing 6 1.657781 0.0134379

ClorfSO #N/A 1.65773 0.04545184

GPE G protein-coupled estrogen receptor 1 1.657069 0.04319093

USP31 ubiquitin specific peptidase 31 1.656917 0.04971698

SEL1L sel-1 suppressor of lin-12-like (C. elegans) 1.656769 0.00073657

LRRC32 #N/A 1.656648 0.01786459

LOC4011 WD repeat domain 5 pseudogene 1.656331 0.01809748

27

ZFR zinc finger RNA binding protein 1.656317 0.01174294

SFRS11 splicing factor, arginine/serine-rich 11 1.655749 0.03570373

DNMT3B #N/A 1.655462 0.0128301 1

LM07 LIM domain 7 1.655296 0.04488696

TMEM87 transmembrane protein 87A 1.654926 0.02492593

A

ATL1 atlastin GTPase 1 1.654834 0.04431799

ATP2C2 ATPase, Ca++ transporting, type 2C, member 2 1.654734 0.00487247

SETDB1 SET domain, bifurcated 1 1.654692 0.02047046

EML4 echinoderm microtubule associated protein like 4 1.654476 0.0281831 1

CAD carbamoyl-phosphate synthetase 2, aspartate 1.654177 0.02206911 transcarbamylase, and dihydroorotase

CADM3 cell adhesion molecule 3 1.65411 0.03872219

IL27RA interleukin 27 receptor, alpha 1.653973 0.01235155

BTBD8 #N/A 1.653912 0.04727336

KLC1 kinesin light chain 1 1.653855 0.02180894

EVI2B ecotropic viral integration site 2B 1.6538 0.0084494

PTCH2 patched homolog 2 (Drosophila) 1.653654 0.04484893

DCTN3 dynactin 3 (p22) 1.653642 0.04236378

ABL2 v-abl Abelson murine leukemia viral oncogene 1.653605 0.02086271 homolog 2 (arg, Abelson-related gene)

BMP7 #N/A 1.65329 0.04358522

TP53BP1 tumor protein p53 binding protein 1 1.653193 0.03890936

UBR2 ubiquitin protein ligase E3 component n-recognin 1.653146 0.04514582

SIK2 salt-inducible kinase 2 1.653097 0.03062801

RPS6KA5 ribosomal protein S6 kinase, 90kDa, polypeptide 5 1.652562 0.02190037

GCET2 germinal center expressed transcript 2 1.652415 0.01231915

GRIN3A #N/A 1.652095 0.00100969

PURG #N/A 1.651864 0.01098373

DPT dermatopontin 1.65179 0.00656735

OR6S1 #N/A 1.651297 0.03715299

FXYD6 FXYD domain containing ion transport regulator 6 1.651286 0.01650285

CCR4 #N/A 1.651135 0.00702746

GJA9 gap junction protein, alpha 9, 59kDa 1.6511 0.00476097

ADNP2 #N/A 1.650976 0.0250456

UBE2F #N/A 1.650727 0.0295403 1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

ABCB8 ATP-binding cassette, sub-family B (MDR/TAP), 1.650682 0.03026619 member 8

CCT4 chaperonin containing TCP1, subunit 4 (delta) 1.650332 0.00525882

CCNB1 cyclin Bl 1.650164 0.00844464

RAB5B RAB5B, member RAS oncogene family 1.649778 0.01497692

POLH polymerase (DNA directed), eta 1.649547 0.02395011

TTYH3 tweety homolog 3 (Drosophila) 1.649217 0.03137991

RASGEF1 RasGEF domain family, member 1C 1.649112 0.00823154

C

SETD2 SET domain containing 2 1.648912 0.00785075

RNF216L ring finger protein 216-like 1.648794 0.04043329

FMNL1 formin-like 1 1.648619 0.03552219

CDRT1 CMT1A duplicated region transcript 1 1.6486 0.04368209

ZC3H12A zinc finger CCCH-type containing 12A 1.648404 0.02926977

SARDH #N/A 1.648399 0.03642761

WDR42A WD repeat domain 42A 1.64808 0.04915726

DLGAP1 discs, large (Drosophila) homolog-associated 1.648077 0.0199561 protein 1

SLC10A7 solute carrier family 10 (sodium/bile acid 1.647486 0.02876396 cotransporter family), member 7

HERC3 hect domain and RLD 3 1.647015 0.02552449

ESR2 estrogen receptor 2 (ER beta) 1.646951 0.0465466

TTF2 transcription termination factor, RNA polymerase 1.646301 0.02857324

II

SESN2 sestrin 2 1.646115 0.02586516 GCNT2 glucosaminyl (N-acetyl) transferase 2, 1-branching 1.645994 0.01314182 enzyme (I blood group)

GANC glucosidase, alpha; neutral C 1.645911 0.02361207 SHMT1 serine hydroxymethyltransferase 1 (soluble) 1.645215 0.02201527 TOR1AIP torsin A interacting protein 1 1.644946 0.03714375 1

C17orf68 chromosome 17 open reading frame 68 1.644674 0.0394161

ZNF280A #N/A 1.644647 0.02664814

Clorfl63 chromosome 1 open reading frame 163 1.644338 0.03337342

WBSCR2 #N/A 1.643667 0.03986954

2

PLCD1 phospholipase C, delta 1 1.643144 0.0318449

IARS2 isoleucyl-tRNA synthetase 2, mitochondrial 1.642147 0.03956772

NLRP14 NLR family, pyrin domain containing 14 1.642087 0.01706756

GNPAT glyceronephosphate O-acyltransferase 1.64205 0.04891731

ELM02 engulfment and cell motility 2 1.641987 0.0301485

KLHL24 kelch-like 24 (Drosophila) 1.641947 0.04076009

EFNA1 #N/A 1.641752 0.02231982

CSF2RB colony stimulating factor 2 receptor, beta, low- 1.64156 0.04305491 affinity (granulocyte-macrophage)

MPST #N/A 1.641559 0.03784384

LYPD1 LY6/PLAUR domain containing 1 1.641321 0.00389105

MFSD6 major facilitator superfamily domain containing 6 1.641239 0.01258127

ZMIZ2 zinc finger, MIZ-type containing 2 1.641094 0.01973167

C6orfl30 chromosome 6 open reading frame 130 1.641034 0.02116154

DB1/ 6943751₆.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P

Symbol Change value

LRIG3 leucine-rich repeats and immunoglobulin-like 1.640951 0.01573077 domains 3

NDRG2 NDRG family member 2 1.640909 0.03953699

KRTAP9- #N/A 1.640856 0.01242767

ARMC9 armadillo repeat containing 9 1.640715 0.03382256

GK5 glycerol kinase 5 (putative) 1.640432 0.0302701

ABHD12 abhydrolase domain containing 12 1.640414 0.04682013

CD320 #N/A 1.640265 0.02338767

ESR1 estrogen receptor 1 1.639735 0.02625181

SCML2 sex comb on midleg-like 2 (Drosophila) 1.63955 0.02882134

JUP junction plakoglobin 1.639367 0.03601004

CCNE1 cyclin El 1.639327 0.02042491

SPTBN1 spectrin, beta, non-erythrocytic 1 1.63907 0.04864738

SMR3B submaxillary gland androgen regulated protein 3B 1.638949 0.04254077

MAP4 microtubule-associated protein 4 1.638744 0.02496588

ZNF655 zinc finger protein 655 1.638668 0.04149755

EML1 echinoderm microtubule associated protein like 1 1.638472 0.03243667

KLHL18 #N/A 1.638189 0.01732901

VWA5A von Willebrand factor A domain containing 5A 1.638175 0.02082048

FAM71C #N/A 1.638021 0.0465821

GKN1 gastrokine 1 1.637975 0.00765112

XP05 Exportin 5 1.637723 0.02103416

ZAN zonadhesin 1.637693 0.03842288

C2orf53 chromosome 2 open reading frame 53 1.637664 0.03147439

Cl lorf44 chromosome 11 open reading frame 44 1.637585 0.03718475

TDH L-threonine dehydrogenase 1.637032 0.03673551

SLC45A3 solute carrier family 45, member 3 1.63698 0.04169503

UGT1A8 #N/A 1.635808 0.0434691 1

ETNK2 ethanolamine kinase 2 1.635709 0.01409824

Clorfl l2 chromosome 1 open reading frame 112 1.635579 0.00992461

PGBD1 #N/A 1.635302 0.02192783

TAZ tafazzin 1.63491 0.01976788

SERPI A serpin peptidase inhibitor, clade A (alpha- 1 1.634757 0.01211292

J antiproteinase, antitrypsin), member 3

NOTUM #N/A 1.634692 0.03671723

C18orf8 chromosome 18 open reading frame 8 1.634415 0.00563552

CPSF4 cleavage and polyadenylation specific factor 4, 1.634271 0.0401902

30kDa

SBDSP Shwachman-Bodian-Diamond syndrome 1.634196 0.00277558 pseudogene

ATG7 ATG7 autophagy related 7 homolog (S. cerevisiae) 1.633882 0.03310848

CACNA1 calcium channel, voltage-dependent, R type, alpha 1.633405 0.03050823

E IE subunit

TMEM13 #N/A 1.633247 0.04015418 o

MTMR6 myotubularin related protein 6 1.633111 0.04210798

CCDC96 coiled-coil domain containing 96 1.632721 0.00132894

KLF8 Kruppel-like factor 8 1.632665 0.04518306

CREB3 cAMP responsive element binding protein 3 1.632661 0.0380793 Supplemental Table 2 Gene Transcripts Uprcgulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

IZUMOl izumo sperm-egg fusion 1 1.632556 0.0152677 CCDC151 coiled-coil domain containing 151 1.632357 0.02205364 EXTL3 #N/A 1.632321 0.04837552 ERBB4 v-erb-a erythroblastic leukemia viral oncogene 1.632268 0.01693918 homolog 4 (avian)

SETD4 SET domain containing 4 1.632159 0.04029087 MCM7 minichromosome maintenance complex 1.632054 0.02622018 component 7

GPX2 #N/A 1.631438 0.01078967

ZNHIT1 #N/A 1.630944 0.03475841

AMPD2 adenosine monophosphate deaminase 2 1.63062 0.04068794

PvNGTT R A guanylyltransferase and 5'-phosphatase 1.630394 0.03077662

ISY1 ISY1 splicing factor homolog (S. cerevisiae) 1.630243 0.00860759

RFX5 regulatory factor X, 5 (influences HLA class II 1.63004 0.02507788 expression)

DUSP14 #N/A 1.629513 0.03743221 PACSIN2 protein kinase C and casein kinase substrate in 1.629416 0.01854641 neurons 2

CDC2L5 Cell division cycle 2-like 5 (cholinesterase-related 1.629232 0.02372003 cell division controller)

AGBL4 ATP/GTP binding protein-like 4 1.62914 0.01689332

DCLRE1 DNA cross-link repair IB (PS02 homolog, S. 1.628759 0.04794598

B cerevisiae)

KLHL32 kelch-like 32 (Drosophila) 1.628517 0.04424856

BLK B lymphoid tyrosine kinase 1.628505 0.0313156

TRPM7 transient receptor potential cation channel, 1.628499 0.02783676 subfamily M, member 7

RNF170 ring finger protein 170 1.628178 0.03156258 MIER3 mesoderm induction early response 1, family 1.628174 0.01490144 member 3

MX1 myxovirus (influenza virus) resistance 1 , 1.628158 0.04340208 interferon-inducible protein p78 (mouse)

RABGAP RAB GTPase activating protein 1 -like 1.628143 0.04352724 1L

METTL2 methyltransferase like 2A 1.627822 0.01062648 A

CNOT10 CCR4-NOT transcription complex, subunit 10 1.627757 0.02486744 TCEB2 transcription elongation factor B (SHI), 1.627719 0.03178226 polypeptide 2 (18kDa, elongin B)

CUL1 cullin 1 1.627524 0.03912367

HSF2BP heat shock transcription factor 2 binding protein 1.627338 0.0129484

PDIK1L PDLIM1 interacting kinase 1 like 1.627183 0.03847401

DLG4 discs, large homolog 4 (Drosophila) 1.62656 0.03446465

AD adenosine kinase 1.626424 0.0464659

KIF3C kinesin family member 3C 1.626414 0.01997377

KRT86 #N/A 1.625703 0.02397988

ZNF543 zinc finger protein 543 1.625441 0.03427418

GBF1 golgi brefeldin A resistant guanine nucleotide 1.625387 0.02183229 exchange factor 1

ICAM5 intercellular adhesion molecule 5, telencephalin 1.625377 0.04795445

DB l/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

HOXB7 homeobox B7 1.625337 0.02032398

SLC39A1 solute carrier family 39 (zinc transporter), member 1.625181 0.02637379

3 13

PNKP polynucleotide kinase 3 '-phosphatase 1.624848 0.00781074 SILV silver homolog (mouse) 1.62477 0.00568004 CDH3 cadherin 3, type 1, P-cadherin (placental) 1.624713 0.01152246 PIK3R2 phosphoinositide-3-kinase, regulatory subunit 2 1.6247 0.04549777

(beta)

I TS7 integrator complex subunit 7 1.624478 0.04201484

TRIM16 tripartite motif-containing 16 1.624409 0.0204917

RSPH1 #N/A 1.624223 0.00789075

NGLY1 N-glycanase l 1.624181 0.01133855

OR8U1 #N/A 1.623929 0.01915999

PLXNA1 plexin Al 1.623848 0.01642974

TRPT1 TRNA phosphotransferase 1 1.623538 0.01647146

CLSTN1 calsyntenin l 1.623255 0.03128379

ATP2C1 ATPase, Ca++ transporting, type 2C, member 1 1.623069 0.02035012

DHX16 DEAH (Asp-Glu-Ala-His) box polypeptide 16 1.622514 0.03058077

ADAM 10 ADAM metallopeptidase domain 10 1.622498 0.02080203

CDC2L6 Cell division cycle 2-like 6 (CDK8-like) 1.622378 0.01975908

FLAD1 FAD1 flavin adenine dinucleotide synthetase 1.622301 0.03145574 homolog (S. cerevisiae)

CDC25A cell division cycle 25 homolog A (S. pombe) 1.621755 0.03357124 KIAA043 IAA0430 1.621552 0.01950306 0

IFRD2 interferon-related developmental regulator 2 1.621513 0.02552217 GLP1R glucagon-like peptide 1 receptor 1.621275 0.04657262 ACSS2 acyl-CoA synthetase short-chain family member 2 1.621256 0.03220868 AKR1C3 aldo-keto reductase family 1, member C3 (3-alpha 1.621068 0.03304111 hydroxysteroid dehydrogenase, type II)

FOXP1 forkhead bo Pl 1.621009 0.01077085

TRIML1 tripartite motif family-like 1 1.62081 0.04904316

AP3B2 adaptor-related protein complex 3, beta 2 subunit 1.620796 0.01152866

ACSL4 acyl-CoA synthetase long-chain family member 4 1.620361 0.01663773

UIMC1 ubiquitin interaction motif containing 1 1.619904 0.0123412

GSTK1 glutathione S-transferase kappa 1 1.619571 0.02169514

SLC30A5 solute carrier family 30 (zinc transporter), member 1.619372 0.00611784

5

GNRHR gonadotropin-releasing hormone receptor 1.619112 0.01836612 MAGI3 membrane associated guanylate kinase, WW and 1.619074 0.0347533

PDZ domain containing 3

KCNS3 #N/A 1.61907 0.0384468

GOLM1 golgi membrane protein 1 1.619055 0.02770539

PPIL2 peptidylprolyl isomerase (cyclophilin)-like 2 1.619019 0.03839263

BBS9 Bardet-Biedl syndrome 9 1.618971 0.02545215

C14orfl66 chromosome 14 open reading frame 166B 1.618766 0.01727413

B

FAM13A family with sequence similarity 13, member A 1.618222 0.04696473

ZNF337 zinc finger protein 337 1.618164 0.04917179

SCRN1 secernin l 1.618146 0.0234382

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P

Symbol Change value

RIOK1 RIO kinase 1 (yeast) 1.618073 0.02088876

ZDHHC2 Zinc finger, DHHC-type containing 20 1.617842 0.01970808 nj

KCNAB2 potassium voltage-gated channel, shaker-related 1.617684 0.03981078 subfamily, beta member 2

ATP7A ATPase, Cu++ transporting, alpha polypeptide 1.617624 0.00244911

ZNF350 zinc finger protein 350 1.617613 0.03540954

AK2 adenylate kinase 2 1.617525 0.02250204

ONECUT #N/A 1.617494 0.0193396

Δ 9

DOCK11 dedicator of cytokinesis 11 1.617408 0.01499409

THRSP thyroid hormone responsive (SPOT 14 homolog, 1.617243 0.01840825

L ai J

MATN2 matrilin 2 1.617111 0.03774538

NOL3 nucleolar protein 3 (apoptosis repressor with 1.616781 0.04753178

CARD domain)

CCDC64 coiled-coil domain containing 64 1.616608 0.01778892

TXNDC1 thioredoxin domain containing 12 (endoplasmic 1.616508 0.04404119

2 reticulum)

TAF11 TAF11 RNA polymerase II, TATA box binding 1.616355 0.04944223 protein (TBP)-associated factor, 28kDa

PRKAGl protein kinase, AMP-activated, gamma 1 non- 1.616205 0.01400252 catalytic subunit

TNFRSF1 tumor necrosis factor receptor superfamily, 1.6161 16 0.028242 oc member 10c, decoy without an intracellular

domain

SRD5A3 steroid 5 alpha-reductase 3 1.615868 0.02133345

COR02B coronin, actin binding protein, 2B 1.615597 0.02201055

ARMC2 armadillo repeat containing 2 1.615273 0.04917875

C15orf28 #N/A 1.615065 0.04881938

AD AMI 5 ADAM metallopeptidase domain 15 1.615013 0.04295632

GTF2IRD GTF2I repeat domain containing 2 1.614706 0.0087574

MATR3 matrin 3 1.614624 0.01811932

AMDHD1 amidohydrolase domain containing 1 1.613868 0.04706021

NAAA N-acylethanolamine acid amidase 1.613809 0.02682593

ANKRD2 ankyrin repeat domain 26 1.613804 0.02691717 f u.

PTCD3 Pentatricopeptide repeat domain 3 1.613309 0.04131451

ACOT4 acyl-CoA thioesterase 4 1.612309 0.01303749

BAT3 HLA-B associated transcript 3 1.612256 0.02485149

SLC1A2 #N/A 1.612239 0.02701275

GSDMC gasdermin C 1.612099 0.03494167

IL2RA #N/A 1.612085 0.0011411

MEGF8 multiple EGF-like-domains 8 1.611731 0.04800507

LTK leukocyte receptor tyrosine kinase 1.61166 0.03101757

SUCLG2 succinate-CoA ligase, GDP-forming, beta subunit 1.61146 0.01434601

WDR3 WD repeat domain 3 1.611359 0.04273902

TNFSF12 tumor necrosis factor (ligand) superfamily, 1.610842 0.03875184 member 12

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

ASH2L ash2 (absent, small, or homeotic)-like (Drosophila) 1.610829 0.02280295

CUZD1 CUB and zona pellucida-like domains 1 1.61066 0.036731 16

CDK7 cyclin-dependent kinase 7 1.61064 0.04970104

BSPRY #N/A 1.610422 0.03152908

SLC5A12 solute carrier family 5 (sodium/glucose 1.610288 0.02608645 cotransporter), member 12

DHX58 DEXH (Asp-Glu-X-His) box polypeptide 58 1.610267 0.00745079

CPB2 carboxypeptidase B2 (plasma) 1.610111 0.00791195

CLU clusterin 1.609789 0.01774065

C21orf81 Chromosome 21 open reading frame 81 1.609735 0.02571931

ADRBK1 adrenergic, beta, receptor kinase 1 1.60958 0.04747509

ASCC3 activating signal cointegrator 1 complex subunit 3 1.609556 0.03484109

HPSE heparanase 1.609469 0.02739996

CHD9 chromodomain helicase DNA binding protein 9 1.609356 0.04390294

CYP4B1 cytochrome P450, family 4, subfamily B, 1.60928 0.03068933 polypeptide 1

FBX04 F-box protein 4 1.609254 0.0305442

TRIM72 #N/A 1.609243 0.02288382

TMEM31 #N/A 1.60898 0.00892839

MEGF10 multiple EGF-like-domains 10 1.60862 0.03073571

ZNF567 zinc finger protein 567 1.608258 0.00974876

DDR1 discoidin domain receptor tyrosine kinase 1 1.608256 0.03840132

ZNHIT3 zinc finger, HIT type 3 1.608113 0.03646061

UQCC ubiquinol-cytochrome c reductase complex 1.608051 0.04468544 chaperone

ZMYM6 zinc finger, MYM-type 6 1.607937 0.03222668

LGALS8 lectin, galactoside-binding, soluble, 8 1.607202 0.03947108

C1QTNF5 Clq and tumor necrosis factor related protein 5 1.607031 0.01353479

DMKN dermokine 1.607017 0.01687905

ITGBL1 integrin, beta-like 1 (with EGF-like repeat 1.606994 0.0452156 domains)

C3orf67 #N/A 1.60672 0.03567027 CYP24A1 cytochrome P450, family 24, subfamily A, 1.606438 0.02869597 polypeptide 1

UHRF1BP UHRF1 binding protein 1 1.606348 0.03018077 1

ZFP30 #N/A 1.606079 0.04811928

AMY1A amylase, alpha 1A (salivary) 1.606035 0.04665085

BRD9 bromodomain containing 9 1.605968 0.02485162

SBN02 strawberry notch homolog 2 (Drosophila) 1.60563 0.02050891

LAMA3 laminin, alpha 3 1.60535 0.04047009

JUN jun oncogene 1.60477 0.01920584

DEN D2 DENN/MADD domain containing 2D 1.604585 0.0490579 D

HP1BP3 heterochromatin protein 1 , binding protein 3 1.604565 0.02598613 ITGAM integrin, alpha M (complement component 3 1.604305 0.03035087 receptor 3 subunit)

AMMEC AMME chromosomal region gene 1 -like 1.604173 0.01373426

R1L

Clorf93 chromosome 1 open reading frame 93 1.604147 0.04881347 1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P

Symbol Change value

PMS2CL #N/A 1.60402 0.01335582 MY018B myosin XVIIIB 1.603928 0.04918494 OR4A16 olfactory receptor, family 4, subfamily A, member 1.60381 0.02967072

16

PDLIM2 PDZ and LIM domain 2 (mystique) 1.603215 0.02290454

SMYD1 #N/A 1.602613 0.03160765

VTA1 Vps20-associated 1 homolog (S. cerevisiae) 1.602593 0.04573813

ACSF2 acyl-CoA synthetase family member 2 1.602582 0.04822356

CEACAM carcinoembryonic antigen-related cell adhesion 1.602541 0.02459421

3 molecule 3

MTM1 #N/A 1.602123 0.03943243 AAAS achalasia, adrenocortical insufficiency, alacrimia 1.601908 0.0452572

(Allgrove, triple- A)

GFPT2 glutamine-fructose-6-phosphate transaminase 2 1.601761 0.00786173

NLGN2 neuroligin 2 1.601549 0.02665695

RBP3 retinol binding protein 3, interstitial 1.601508 0.04403107

ATF6 activating transcription factor 6 1.601489 0.03023811

MAN1B1 mannosidase, alpha, class IB, member 1 1.60138 0.02061913

CDH5 cadherin 5, type 2 (vascular endothelium) 1.601346 0.04208751

SLC1A4 solute carrier family 1 (glutamate/neutral amino 1.601111 0.01714116 acid transporter), member 4

TK2 thymidine kinase 2, mitochondrial 1.60101 0.04195181 CITED2 Cbp/p300-interacting transactivator, with 1.600362 0.04147867

Glu/Asp-rich carboxy-terminal domain, 2

FAF2 Fas associated factor family member 2 1.600215 0.00209179 ERP44 endoplasmic reticulum protein 44 1.600078 0.02573524 PLSCR3 #N/A 1.599948 0.00947326 CHTF18 CTF18, chromosome transmission fidelity factor 1.599627 0.04534168

18 homolog (S. cerevisiae)

MRC2 mannose receptor, C type 2 1.59955 0.01292167

C16orf82 chromosome 16 open reading frame 82 1.59918 0.02872845

KLB klotho beta 1.599102 0.01424179

DDR2 discoidin domain receptor tyrosine kinase 2 1.598951 0.03041582

AFAP1 actin filament associated protein 1 1.598905 0.04563362

AK3L1 adenylate kinase 3 -like 1 1.598791 0.01572813

C8orf33 chromosome 8 open reading frame 33 1.598778 0.03554831

TMEM20 transmembrane protein 206 1.598312 0.00827525

6

TSGA13 Testis specific, 13 1.597388 0.03964771

LRRK1 leucine-rich repeat kinase 1 1.596944 0.01369564

CASP1 caspase 1, apoptosis-related cysteine peptidase 1.596901 0.04141203

(interleukin 1 , beta, convertase)

PPAN- PPAN-P2RY11 readthrough 1.596832 0.02509514

P2RY11

APEH N-acylaminoacyl-peptide hydrolase 1.596762 0.03121484

FBX018 F-box protein, helicase, 18 1.59676 0.02376201

SLITRK3 SLIT and NTRK-like family, member 3 1.596757 0.031 19089

LOC1510 #N/A 1.596188 0.03293784

09

CDC14A CDC14 cell division cycle 14 homolog A (S. 1.595892 0.00154532

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

cerevisiae)

RP 1 L 1 retinitis pigmentosa 1 -like 1 1.59584 0.04913338 DACH2 dachshund homolog 2 (Drosophila) 1.595531 0.01838976 TMEM16 #N/A 1.595419 0.00108249

PGGT1B #N/A 1.59504 0.03890081

MTMR 10 myotubularin related protein 10 1.594912 0.01191

PvDHl 1 retinol dehydrogenase 11 (all-trans/9-cis/l 1-cis) 1.594865 0.03426753

SLC12A6 solute carrier family 12 (potassium/chloride 1.594721 0.01361639 transporters), member 6

PR AAl protein kinase, AMP-activated, alpha 1 catalytic 1.594463 0.04465486 subunit

TRRAP transformation/transcription domain-associated 1.593929 0.041873 protein

ANK2 ankyrin 2, neuronal 1.593848 0.04658378 TSC1 tuberous sclerosis 1 1.593378 0.0306092

C2CD2 C2 calcium-dependent domain containing 2 1.593314 0.04277642 URM1 #N/A 1.593008 0.0381188 FBXOl l F-box protein 11 1.592841 0.0041492

SH3BP5 SH3-domain binding protein 5 (BTK-associated) 1.592836 0.02379332

B9D1 B 9 protein domain 1 1.592734 0.00875643

AFF4 AF4/FMR2 family, member 4 1.592172 0.03735867

GRK7 G protein-coupled receptor kinase 7 1.592054 0.02158491

C9orfl40 chromosome 9 open reading frame 140 1.59201 0.03023132

NF2 neurofibromin 2 (merlin) 1.591993 0.03518012

ATP13 A3 ATPase type 13 A3 1.591824 0.04776691

PIK3R4 phosphoinositide-3-kinase, regulatory subunit 4 1.591757 0.04118887

UNQ6167 #N/A 1.591575 0.01460981

SMG6 Smg-6 homolog, nonsense mediated mRNA decay 1.591296 0.02366313 factor (C. elegans)

TEP1 telomerase-associated protein 1 1.591249 0.007113

ADAMTS ADAMTS-like 1 1.591238 0.0346295 LI

JTB jumping translocation breakpoint 1.59121 0.00645786

HEXB hexosaminidase B (beta polypeptide) 1.591 169 0.03643068 CDC42BP CDC42 binding protein kinase gamma (DMPK- 1.591157 0.03515532 G like)

UBR3 ubiquitin protein ligase E3 component n-recognin 1.591072 0.03510366

3 (putative)

TTC13 tetratricopeptide repeat domain 13 1.591059 0.01200634

CEP76 centrosomal protein 76kDa 1.59072 0.03796653

CTNND2 catenin (cadherin-associated protein), delta 2 1.590564 0.04139833

(neural plakophilin-related arm-repeat protein)

COG2 component of oligomeric golgi complex 2 1.590559 0.03938693 ZNF250 #N/A 1.590509 0.03867041 TWSG1 Twisted gastrulation homolog 1 (Drosophila) 1.590384 0.03366619 BBS 12 Bardet-Biedl syndrome 12 1.590323 0.04737214

ABCC8 ATP-binding cassette, sub-family C (CFTR/MRP), 1.589974 0.02165076 member 8

WNK1 WNK lysine deficient protein kinase 1 1.589806 0.03200462

DB l/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

C6orfl 14 #N/A 1.58954 0.01063591

LYSMD2 LysM, putative peptidoglycan-binding, domain 1.589339 0.02093268 containing 2

BRSK1 BR serine/threonine kinase 1 1.589014 0.03200387

PCDHGA protocadherin gamma subfamily A, 9 1.58873 0.02384119 q

EAF1 ELL associated factor 1 1.588657 0.02722721

TYW1B tRNA-yW synthesizing protein 1 homolog B (S. 1.588492 0.0202829 cerevisiae)

LPCAT2 lysophosphatidylcholine acyltransferase 2 1.588151 0.02446608

SPAG5 sperm associated antigen 5 1.588074 0.0223564

HNF1B HNF1 homeobox B 1.587917 0.0471151

RAB22A RAB22A, member RAS oncogene family 1.587841 0.00540586

CRX cone-rod homeobox 1.587767 0.02490908

TADA2L Transcriptional adaptor 2 (ADA2 homolog, yeast)- 1.587709 0.01967787

UJvC

SMC IB structural maintenance of chromosomes IB 1.587648 0.0335672

VPS8 vacuolar protein sorting 8 homolog (S. cerevisiae) 1.587643 0.02836086

HELLS helicase, lymphoid-specific 1.587547 0.04955739

QRICH2 glutamine rich 2 1.587423 0.04650146

EXTL1 exostoses (multiple)-like 1 1.587242 0.0062661 1

KCNK1 potassium channel, subfamily K, member 1 1.587052 0.03835799

CYP27B1 cytochrome P450, family 27, subfamily B, 1.586904 0.00724345 polypeptide 1

RAB2B #N/A 1.586842 0.02741108

ATP6V1C ATPase, H+ transporting, lysosomal 42kDa, V 1 1.586738 0.01862375

2 subunit C2

PHLDB3 #N/A 1.586628 0.04403771

PTPRF protein tyrosine phosphatase, receptor type, F 1.586443 0.00015476

ARMCX5 armadillo repeat containing, X-linked 5 1.586281 0.02579047

KLHL13 kelch-like 13 (Drosophila) 1.585801 0.03290522

LM02 #N/A 1.585683 0.01178633

MMP19 matrix metallopeptidase 19 1.585515 0.04827345

CCNYL1 cyclin Y-like 1 1.585471 0.02078159

IKBKE inhibitor of kappa light polypeptide gene enhancer 1.585318 0.02560331 in B-cells, kinase epsilon

FUR Fl 1 receptor 1.585065 0.04318684

GUCY2C guanylate cyclase 2C (heat stable enterotoxin 1.584901 0.0258845 receptor)

SAP130 Sin3A-associated protein, 130kDa 1.584898 0.02084365

C1QTNF4 #N/A 1.584857 0.00443819

CSMD2 CUB and Sushi multiple domains 2 1.584718 0.04266615

SDK2 sidekick homolog 2 (chicken) 1.584691 0.00472839

AD AM 17 ADAM metallopeptidase domain 17 1.584644 0.02422915

ATR ataxia telangiectasia and Rad3 related 1.584356 0.02047599

IFT88 intraflagellar transport 88 homolog 1.584235 0.03689187

(Chlamydomonas)

DNMT3L DNA (cytosine-5-)-methyltransferase 3-like 1.584131 0.02732209

TRIM2 tripartite motif-containing 2 1.583354 0.02097093

NAT 15 N-acetyltransf erase 15 (GCN5 -related, putative) 1.583249 0.01793565

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P

Symbol Change value

PPBP pro-platelet basic protein (chemokine (C-X-C 1.583184 0.04417932 motif) ligand 7)

SORCS1 sortilin-related VPS 10 domain containing receptor 1.583089 0.00145216

1

PTPRK protein tyrosine phosphatase, receptor type, K 1.582954 0.03883168 ERCC6 excision repair cross-complementing rodent repair 1.582855 0.03693582 deficiency, complementation group 6

C19orf45 chromosome 19 open reading frame 45 1.582827 0.01372364 NARG1L NMDA receptor regulated 1 -like 1.582732 0.01 1411 16 PPAP2A phosphatidic acid phosphatase type 2A 1.582666 0.00144035 DYSF dysferlin, limb girdle muscular dystrophy 2B 1.582554 0.02005849

(autosomal recessive)

ADAM23 ADAM metallopeptidase domain 23 1.582461 0.03598515 CDH8 cadherin 8, type 2 1.582411 0.01416816 COG3 component of oligomeric golgi complex 3 1.58219 0.03076747 PDE4D phosphodiesterase 4D, cAMP-specific 1.582152 0.03999691

(phosphodiesterase E3 dunce homolog,

Drosophila)

POT1 protection of telomeres 1 homolog (S. pombe) 1.582129 0.00425704

ATP1A1 ATPase, Na+/K+ transporting, alpha 1 polypeptide 1.582011 0.01059971

GRIK4 #N/A 1.581954 0.03740164

ZNF397 zinc finger protein 397 1.581557 0.0359701

CCDC50 coiled-coil domain containing 50 1.581327 0.02701904

FLJ13197 hypothetical FLJ13197 1.580835 0.02393229

EMD #N/A 1.580701 0.0428735

RASA3 RAS p21 protein activator 3 1.580655 0.03063955

FAM40B family with sequence similarity 40, member B 1.580347 0.014431 12

MME membrane metallo-endopeptidase 1.580337 0.00628201

AARSD1 alanyl-tRNA synthetase domain containing 1 1.580146 0.0094374

RDH12 retinol dehydrogenase 12 (all-trans/9-cis/l 1-cis) 1.579889 0.03674629

HTATIP2 HIV-1 Tat interactive protein 2, 30kDa 1.579603 0.03605033

SDCBP syndecan binding protein (syntenin) 1.579519 0.0221665

C10orfl40 chromosome 10 open reading frame 140 1.579379 0.02057772

CAPN11 calpain 11 1.579255 6.95E-05

KANK1 KN motif and ankyrin repeat domains 1 1.578484 0.0289754

ASPH aspartate beta-hydroxylase 1.57833 0.03437934

TSR1 TSR1, 20S rRNA accumulation, homolog (S. 1.578152 0.01061894 cerevisiae)

TRABD TraB domain containing 1.578042 0.00509686

EPHB4 EPH receptor B4 1.577896 0.04990407

ATP6V1A ATPase, H+ transporting, lysosomal 70kDa, VI 1.57784 0.02526282 subunit A

CELSR1 cadherin, EGF LAG seven-pass G-type receptor 1 1.577518 0.04498579

(flamingo homolog, Drosophila)

MFSD9 major facilitator superfamily domain containing 9 1.577044 0.00544493

ZDHHC2 zinc finger, DHHC-type containing 2 1.576589 0.00927643

DSC3 desmocollin 3 1.576479 0.02893414

CROCCL ciliary rootlet coiled-coil, rootletin-like 1 1.576179 0.02536792

1

TNFRSF6 #N/A 1.575991 0.03266746 1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P

Symbol Change value

B

ATP2B2 ATPase, Ca++ transporting, plasma membrane 2 1.575985 0.03812112

APOB apolipoprotein B (including Ag(x) antigen) 1.575935 0.01844524

ID2 inhibitor of DNA binding 2, dominant negative 1.575791 0.03728961 helix-loop-helix protein

TMEM44 #N/A 1.575589 0.04537621

CACNA2 calcium channel, voltage-dependent, alpha 2/delta 1.575574 0.04508288

D2 subunit 2

LSAMP #N/A 1.575408 0.01726092

AFG3L1 AFG3 ATPase family gene 3-like 1 (S. cerevisiae) 1.575401 0.02287511

C17orf63 chromosome 17 open reading frame 63 1.575341 0.04826082

BACE2 beta-site APP-cleaving enzyme 2 1.575246 0.02393872

FAM160A family with sequence similarity 160, member A2 1.575216 0.04868855

ER 1 endoplasmic reticulum to nucleus signaling 1 1.575111 0.01643217

GNPTG N-acetylglucosamine- 1 -phosphate transferase, 1.575093 0.03895541 gamma subunit

GAGE1 G antigen 1 1.574721 0.01644645

SCAMPI secretory carrier membrane protein 1 1.57467 0.02157253

MAP3K10 mitogen-activated protein kinase kinase kinase 10 1.5746 0.01164556

GBE1 glucan (1,4-alpha-), branching enzyme 1 1.57458 0.04179094

CP ceruloplasmin (ferroxidase) 1.574574 0.03721093

E2F5 E2F transcription factor 5, pl30-binding 1.574504 0.04111575

POU5F1 POU class 5 homeobox 1 1.574427 0.03206344

GDF7 Growth differentiation factor 7 1.574369 0.01239241

USP12 ubiquitin specific peptidase 12 1.574275 0.0169693

SLC13A4 solute carrier family 13 (sodium/sulfate 1.573872 0.02546365 symporters), member 4

SNHG7 #N/A 1.573774 0.0131859

BAGE B melanoma antigen 1.573499 0.00573789

IQWD1 IQ motif and WD repeats 1 1.573388 0.00690926

POLE2 polymerase (DNA directed), epsilon 2 (p59 1.573351 0.0499254 subunit)

CDKL1 cyclin-dependent kinase-like 1 (CDC2 -related 1.573026 0.03198318 kinase)

SNAPC3 small nuclear R A activating complex, 1.572895 0.04873285 polypeptide 3, 50kDa

ALMS1 Alstrom syndrome 1 1.57257 0.03754191

USP20 ubiquitin specific peptidase 20 1.572495 0.00964908

OLA1 Obg-like ATPase 1 1.57241 0.02014899

SLC35B4 solute carrier family 35, member B4 1.572356 0.03579128

TRAF5 TNF receptor-associated factor 5 1.572202 0.0118116

SIM2 single-minded homolog 2 (Drosophila) 1.57188 0.0363994

KLK7 kallikrein-related peptidase 7 1.571556 0.00602879

FAM107B family with sequence similarity 107, member B 1.571462 0.0499209

MYL10 #N/A 1.571408 0.019907

UMODL1 uromodulin-like 1 1.571159 0.03245662

CTN A1 catenin (cadherin-associated protein), alpha 1 , 1.57067 0.03967257

102kDa

ZNF540 #N/A 1.5705 0.04629319 1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P

Symbol Change value

VPS35 Vacuolar protein sorting 35 homolog (S. 1.570291 0.04981512 cerevisiae)

SLC37A1 solute carrier family 37 (glycerol-3-phosphate 1.570203 0.0479174 transporter), member 1

LOCI 001 similar to zinc finger protein 799 1.570005 0.03452717 34396

SLC7A11 solute carrier family 7, (cationic amino acid 1.569962 0.03388442 transporter, y+ system) member 11

EZH2 enhancer of zeste homolog 2 (Drosophila) 1.569822 0.03248874

TMEM22 #N/A 1.569714 0.04624286

2

PRPH peripherin 1.569551 0.03010769

DUSP13 dual specificity phosphatase 13 1.569365 0.00698188

IER5 Immediate early response 5 1.569239 0.03059287

JMJD8 jumonji domain containing 8 1.569201 0.00186703

EZH1 enhancer of zeste homolog 1 (Drosophila) 1.569122 0.03681327

ADCK2 aarF domain containing kinase 2 1.568919 0.00764036

MAN2B1 mannosidase, alpha, class 2B, member 1 1.568772 0.00431642

ITIH1 inter-alpha (globulin) inhibitor HI 1.568705 0.04038838

PRKAG3 protein kinase, AMP-activated, gamma 3 non- 1.568554 0.01129936 catalytic subunit

C6orf64 chromosome 6 open reading frame 64 1.568482 0.0473454 KRBA1 KRAB-A domain containing 1 1.568336 0.0353163 PREX2 phosphatidylinositol-3,4,5-trisphosphate- 1.568106 0.03016754 dependent Rac exchange factor 2

PARP14 poly (ADP-ribose) polymerase family, member 14 1.567929 0.04751239

GATSL3 GATS protein-like 3 1.567334 0.01 14682

UBE2CBP ubiquitin-conjugating enzyme E2C binding protein 1.5672 0.04470765

FAM124B #N/A 1.567171 0.01266934

NAT11 N-acetyltransferase 11 1.567117 0.0194771

NCOA6 nuclear receptor coactivator 6 1.567033 0.01622988

VPS26B vacuolar protein sorting 26 homolog B (S. pombe) 1.566785 0.04307642

VDAC3 voltage-dependent anion channel 3 1.566756 0.04059678

GPAM Glycerol-3 -phosphate acyltransf erase, 1.566595 0.01625274 mitochondrial

PARP4 poly (ADP-ribose) polymerase family, member 4 1.566571 0.04244339

TMC03 transmembrane and coiled-coil domains 3 1.566566 0.03901138

PPP2R5D protein phosphatase 2, regulatory subunit B', delta 1.566442 0.0111716

UBE3C ubiquitin protein ligase E3C 1.566387 0.00552304

OR4D6 #N/A 1.566317 0.04814622

SMPDL3 sphingomyelin phosphodiesterase, acid-like 3A 1.566308 0.03912803

A

C18orf45 chromosome 18 open reading frame 45 1.566288 0.00811821 Z F438 zinc finger protein 438 1.566126 0.00965156 RHBDF1 #N/A 1.565929 0.02802746 CDH15 cadherin 15, type 1, M-cadherin (myotubule) 1.565886 0.04710114 PCDH1 1X protocadherin 1 1 X-linked 1.565808 0.03880194 RTTN rotatin 1.565788 0.04473924 PEX3 peroxisomal biogenesis factor 3 1.565712 0.01551155 IQCBl IQ motif containing Bl 1.565602 0.01077869

DB Π 1//66!943751 .1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

TRPM2 transient receptor potential cation channel, 1.565244 0.02674605 subfamily M, member 2

STAT2 signal transducer and activator of transcription 2, 1.565101 0.00586589

113kDa

FLJ44048 FLJ44048 protein 1.564904 0.03758947

AFF3 AF4/FMR2 family, member 3 1.564708 0.0283746

O 3A4 #N/A 1.564682 0.04117352

DVL3 dishevelled, dsh homolog 3 (Drosophila) 1.564642 0.02434656

DNAH11 dynein, axonemal, heavy chain 11 1.564592 0.0414389

NT5C 5', 3 '-nucleotidase, cytosolic 1.56457 0.0446903

SPEN spen homolog, transcriptional regulator 1.564499 0.0233066

(Drosophila)

TMPRSS1 transmembrane protease, serine 13 1.564484 0.0368793 3

C20orfl49 Chromosome 20 open reading frame 149 1.564392 0.00222356

DGKH Diacylglycerol kinase, eta 1.564346 0.0367789

FYCOl FYVE and coiled-coil domain containing 1 1.564045 0.02623964

IL23R interleukin 23 receptor 1.563714 0.00338447

APBA1 amyloid beta (A4) precursor protein-binding, 1.563618 0.02990328 family A, member 1

CACNA1 calcium channel, voltage-dependent, T type, alpha 1.563523 0.01013023 G 1G subunit

SLC9A3R #N/A 1.563271 0.04801348 1

UBE4B ubiquitination factor E4B (UFD2 homolog, yeast) 1.563098 0.04789056 ST13 suppression of tumorigenicity 13 (colon 1.563085 0.02759531 carcinoma) (Hsp70 interacting protein)

THOC3 THO complex 3 1.562977 0.01573792 VTI1A vesicle transport through interaction with t- 1.562647 0.02759378

SNAREs homolog 1A (yeast)

CDK6 cyclin-dependent kinase 6 1.56261 0.02902345

YPEL2 #N/A 1.562551 0.04389314

ATRIP ATR interacting protein 1.562549 0.03935309

FAM170A family with sequence similarity 170, member A 1.562187 0.01403262

AGGF1 angiogenic factor with G patch and FHA domains 1.561939 0.01752432

1

LRP8 Low density lipoprotein receptor-related protein 8, 1.561638 0.01283334 apolipoprotein e receptor

CLEC17A C-type lectin domain family 17, member A 1.561512 0.03881722

TEC Tec protein tyrosine kinase 1.561419 0.04835099

UBE2J1 ubiquitin-conjugating enzyme E2, Jl (UBC6 1.561325 0.03932752 homolog, yeast)

LTBR lymphotoxin beta receptor (TNFR superfamily, 1.56131 0.01734089 member 3)

DBR1 debranching enzyme homolog 1 (S. cerevisiae) 1.560804 0.04423254

ADAM 19 ADAM metallopeptidase domain 19 (meltrin beta) 1.56073 0.01586926

EFHD1 EF-hand domain family, member Dl 1.560486 0.04485476

SGOL2 shugoshin-like 2 (S. pombe) 1.560043 0.03657261

TPP2 tripeptidyl peptidase II 1.559247 0.02199587

UCP2 #N/A 1.558711 0.02231615

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

FCAMR #N/A 1.558696 0.02610126

SPATA21 spermatogenesis associated 21 1.55863 0.04292467

SP100 SP100 nuclear antigen 1.558535 0.04252481

BAIAP2 BAI1 -associated protein 2 1.55851 1 0.02805553

COPZ1 Coatomer protein complex, subunit zeta 1 1.55847 0.02752252

ARFGEF1 ADP-ribosylation factor guanine nucleotide- 1.558221 0.00719994 exchange factor l(brefeldin A-inhibited)

HNF1A F1NF1 homeobox A 1.558103 0.02276896 AAG1 kidney associated antigen 1 1.557843 0.01686161 HUNK hormonally up-regulated Neu-associated kinase 1.557667 0.02915042 HK2 hexokinase 2 1.557123 0.01528673

ECHDC2 enoyl CoA hydratase domain containing 2 1.55701 0.03188733

FGFRIOP FGFR1 oncogene partner 1.556994 0.04220555

SLC20A2 solute carrier family 20 (phosphate transporter), 1.556953 0.02206856 member 2

FLU flightless I homolog (Drosophila) 1.556875 0.03932867

TMEM17 #N/A 1.556793 0.04308751 4

CELSR3 cadherin, EGF LAG seven-pass G-type receptor 3 1.556787 0.03262012

(flamingo homolog, Drosophila)

PSME4 proteasome (prosome, macropain) activator 1.556614 0.00839984 subunit 4

WDR26 WD repeat domain 26 1.556435 0.04076079 FLU Friend leukemia virus integration 1 1.556366 0.04141388

SPAG11A sperm associated antigen 11 A 1.55631 0.04413696

DIAPH2 diaphanous homolog 2 (Drosophila) 1.556277 0.02283721

PHF7 #N/A 1.556238 0.02309381

GDF1 growth differentiation factor 1 1.556024 0.01715961

PNPLA6 patatin-like phospholipase domain containing 6 1.555804 0.03083244

ITGA5 integrin, alpha 5 (fibronectin receptor, alpha 1.555713 0.03160453 polypeptide)

ZAK sterile alpha motif and leucine zipper containing 1.555553 0.04046045 kinase AZK

ZPBP zona pellucida binding protein 1.555489 0.03469015

OR1L6 #N/A 1.555362 0.04907249

BIRC7 baculoviral IAP repeat-containing 7 1.555356 0.00560653

PALB2 partner and localizer of BRCA2 1.554951 0.03269141

GOLPH3 golgi phosphoprotein 3-like 1.554927 0.02287013

L

COL1 1A2 collagen, type XI, alpha 2 1.554906 0.01062953

BTBD9 #N/A 1.554815 0.00414556

IQGAP3 IQ motif containing GTPase activating protein 3 1.554802 0.03180541

ZNF516 zinc finger protein 516 1.554729 0.03327762

INTU inturned planar cell polarity effector homolog 1.554677 0.01093947

(Drosophila)

VAT1L vesicle amine transport protein 1 homolog (T. 1.554477 0.02672044 californica)-like

GAS 8 growth arrest-specific 8 1.55427 0.0138367

PTBP2 polypyrimidine tract binding protein 2 1.553715 0.02025571

MERTK c-mer proto-oncogene tyrosine kinase 1.553644 0.00740715

DB l/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

USP24 ubiquitin specific peptidase 24 1.553516 0.04241653 ZNF703 zinc finger protein 703 1.553516 0.0157481 TMEM12 transmembrane protein 120 A 1.553488 0.03978529 OA

KDM4A lysine (K)-specific demethylase 4A 1.55346 0.00643308

NMI N-myc (and STAT) interactor 1.553368 0.03407941

SLC5A1 solute carrier family 5 (sodium/glucose 1.553159 0.04013204 cotransporter), member 1

FLJ20184 #N/A 1.55307 0.03693891

CCDC55 coiled-coil domain containing 55 1.552793 0.04222151

CCDC45 coiled-coil domain containing 45 1.552779 0.04177711

JAG2 jagged 2 1.552759 0.01734602

GFM1 G elongation factor, mitochondrial 1 1.55256 0.00540147

FCHSD2 FCH and double SH3 domains 2 1.552543 0.03357263

ACY3 aspartoacylase (aminocyclase) 3 1.552438 0.0317794

PSRC1 proline/serine-rich coiled-coil 1 1.552427 0.01596017

SMYD2 SET and MYND domain containing 2 1.552349 0.04941773

FAM164C #N/A 1.552223 0.013121 1

STYXL1 #N/A 1.551782 0.04061065

OSBP2 oxysterol binding protein 2 1.551576 0.00327305

KIAA031 KIAA0317 1.55151 0.0065551

7

ASNS asparagine synthetase (glutamine-hydrolyzing) 1.551478 0.04490557

IER3IP1 immediate early response 3 interacting protein 1 1.551439 0.03462929

IGF1R insulin-like growth factor 1 receptor 1.551408 0.0245575

RBM19 RNA binding motif protein 19 1.551308 0.04234767

TLN2 talin 2 1.550999 0.03609548

SERPINA serpin peptidase inhibitor, clade A (alpha- 1 1.55087 0.0466949

10 antiproteinase, antitrypsin), member 10

ACSL6 acyl-CoA synthetase long-chain family member 6 1.550367 0.02772304

STK32A serine/threonine kinase 32 A 1.549828 0.0158544

ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene 1.549809 0.03913273 homolog 2, neuro/glioblastoma derived oncogene

homolog (avian)

ACER2 alkaline ceramidase 2 1.5498 0.00666805

YIPF3 Yi l domain family, member 3 1.549456 0.04816962

COX17 COX 17 cytochrome c oxidase assembly homolog 1.548985 0.00063577

(S. cerevisiae)

PSMD12 proteasome (prosome, macropain) 26S subunit, 1.54839 0.03297181 non-ATPase, 12

SELENBP selenium binding protein 1 1.548317 0.01943454 1

PSMG1 proteasome (prosome, macropain) assembly 1.548169 0.04325353 chaperone 1

GLB1L3 galactosidase, beta 1-like 3 1.548144 0.04116442

DDX51 DEAD (Asp-Glu- Ala-Asp) box polypeptide 51 1.548135 0.04765583

PRKACG #N/A 1.548002 0.01972037

GSK3A glycogen synthase kinase 3 alpha 1.547597 0.01055153

ELOVL2 elongation of very long chain fatty acids 1.547361 0.02213573

(FENl/Elo2, SUR4/Elo3, yeast)-like 2

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

DYNC1I1 dynein, cytoplasmic 1, intermediate chain 1 1.547255 0.0015712

CD207 CD207 molecule, langerin 1.5472 0.03436793

PIK3C2B phosphoinositide-3-kinase, class 2, beta 1.5472 0.02408928 polypeptide

TTC39A tetratricopeptide repeat domain 39A 1.547186 0.0477246 KIFC2 kinesin family member C2 1.547163 0.00481211 KIAA119 KIAA1199 1.547159 0.02909628 9

LIX1L Lixl homolog (mouse)-like 1.547006 0.03097144 LILRA1 leukocyte immunoglobulin-like receptor, 1.546952 0.02348155 subfamily A (with TM domain), member 1

MLLT10 myeloid/lymphoid or mixed-lineage leukemia 1.546189 0.01475505

(trithorax homolog, Drosophila); translocated to,

10

AP1GBP1 API gamma subunit binding protein 1 1.545631 0.04628375

OFD1 Oral-facial-digital syndrome 1 1.54549 0.02426386

FAM98A family with sequence similarity 98, member A 1.545402 0.02057287

LXN latexin 1.545208 0.04708531

TRA@ T cell receptor alpha locus 1.545191 0.00657499

ZNF189 zinc finger protein 189 1.545129 0.04371332

PTPN18 protein tyrosine phosphatase, non-receptor type 18 1.5449 0.04522658

(brain-derived)

UGCGL1 UDP-glucose ceramide glucosyltransferase-like 1 1.544741 0.01624691 KCNA3 potassium voltage-gated channel, shaker-related 1.544534 0.02801233 subfamily, member 3

C7orf67 #N/A 1.544427 0.03800144

MYLIP myosin regulatory light chain interacting protein 1.544082 0.02225968

C20orfl52 #N/A 1.543931 0.01685434

C6orf81 chromosome 6 open reading frame 81 1.543531 0.00896843

SLC25A3 solute carrier family 25, member 37 1.543338 0.04649296

7

TTC27 tetratricopeptide repeat domain 27 1.543211 0.03112533 PDE6G phosphodiesterase 6G, cGMP-specific, rod, 1.543173 0.01344947 gamma

IFT140 intraflagellar transport 140 homolog 1.543108 0.00515536

(Chlamydomonas)

C3orf20 chromosome 3 open reading frame 20 1.543101 0.04849387

ZBTB47 zinc finger and BTB domain containing 47 1.542984 0.00160036

RENBP renin binding protein 1.542802 0.01242357

TRIM29 tripartite motif-containing 29 1.54276 0.01564357

SEMA3F sema domain, immunoglobulin domain (Ig), short 1.542713 0.00446777 basic domain, secreted, (semaphorin) 3F

TES testis derived transcript (3 LIM domains) 1.542686 0.0424636 HACE1 HECT domain and ankyrin repeat containing, E3 1.542661 0.02637332 ubiquitin protein ligase 1

SPAM1 sperm adhesion molecule 1 (PH-20 hyaluronidase, 1.542344 0.01501086 zona pellucida binding)

LAT2 linker for activation of T cells family, member 2 1.542234 0.02423761

PDIA6 protein disulfide isomerase family A, member 6 1.541958 0.00282884

HGD homogentisate 1,2-dioxygenase 1.541734 0.03666332

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

ZWI T ZW10 inter actor 1.541193 0.00639813

SLC47A1 solute carrier family 47, member 1 1.540958 0.0236242

USP2 ubiquitin specific peptidase 2 1.540856 0.04579272

ADCY5 adenylate cyclase 5 1.540403 0.04203521

CCDC13 coiled-coil domain containing 13 1.540379 0.03994005

RNF112 #N/A 1.539982 0.03805617

WDR13 WD repeat domain 13 1.53985 0.02618777

AMICA1 Adhesion molecule, interacts with CXADR 1.539542 0.01280107 antigen 1

SLC4A10 solute carrier family 4, sodium bicarbonate 1.53954 0.03531248 transporter, member 10

DSC2 desmocollin 2 1.539479 0.04756335

HERV- #N/A 1.539437 0.04566891

FRD

ZNF643 zinc finger protein 643 1.53922 0.02783205

PARP16 poly (ADP-ribose) polymerase family, member 16 1.538958 0.04677215

HOXD13 homeobox D13 1.538795 0.00363393

DDX11 DEAD/H (Asp-Glu- Ala-Asp/His) box polypeptide 1.538718 0.04766504

11 (CHLl-like helicase homolog, S. cerevisiae)

HOXA11 homeobox Al l 1.538588 0.01564044

MDH1 malate dehydrogenase 1, NAD (soluble) 1.538547 0.0350328

FARSA #N/A 1.538532 0.04749653

OLIG2 #N/A 1.538087 0.01262021

PBX2 pre-B-cell leukemia homeobox 2 1.537608 0.01562364

PCDHGB #N/A 1.53751 0.04615183

3

TMEM17 transmembrane protein 173 1.537442 0.03398467 3

KLK13 #N/A 1.537286 0.00357254

HIP1 huntingtin interacting protein 1 1.537285 0.04332192

AOX1 aldehyde oxidase 1 1.537229 0.04739972

C20orf96 #N/A 1.537172 0.0308458

GRIN2C glutamate receptor, ionotropic, N-methyl D- 1.536935 0.02623653 aspartate 2C

STXBP5 syntaxin binding protein 5 (tomosyn) 1.536748 0.00536101

CYFIP2 cytoplasmic FMR1 interacting protein 2 1.536689 0.04088386

MED28 mediator complex subunit 28 1.53664 0.01080206

GRIA4 glutamate receptor, ionotrophic, AMPA 4 1.536595 0.01793461

HEATR4 HEAT repeat containing 4 1.536414 0.01645114

FANCA Fanconi anemia, complementation group A 1.536412 0.00551397

FAHD2A fumarylacetoacetate hydrolase domain containing 1.536351 0.00138557

2A

TBC1D13 #N/A 1.536327 0.04038732

ROR2 receptor tyrosine kinase-like orphan receptor 2 1.536322 0.04734429

ABCA1 ATP -binding cassette, sub-family A (ABC1), 1.53626 0.0201419 member 1

CEBPB CCAAT/enhancer binding protein (C/EBP), beta 1.536196 0.00556252 Clorf52 chromosome 1 open reading frame 52 1.536076 0.00413615 MORC3 MORC family CW-type zinc finger 3 1.535949 0.0052928 CDC42SE CDC42 small effector 1 1.535703 0.04839242

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

1

PIK3C2G phosphoinositide-3 -kinase, class 2, gamma 1.535554 0.03320153 polypeptide

PHF16 PHD finger protein 16 1.535433 0.01452813

KIAA121 KIAA1217 1.535428 0.03370106

7

POLA2 polymerase (DNA directed), alpha 2 (70kD 1.535227 0.01959815 subunit)

RBM42 #N/A 1.534781 0.0450143 TFE3 transcription factor binding to IGHM enhancer 3 1.534772 0.01746548 TMEM22 transmembrane protein 220 1.534598 0.01084762 0

Clorfl09 chromosome 1 open reading frame 109 1.534453 0.02284748 BCAT2 branched chain amino-acid transaminase 2, 1.534292 0.04597044 mitochondrial

U Q6493 #N/A 1.53402 0.01826442 TBKBP1 TBK1 binding protein 1 1.533859 0.01832024 PPP1R12 #N/A 1.533806 0.01552649 B

FANCM #N/A 1.533762 0.04244972

NID2 nidogen 2 (osteonidogen) 1.533745 0.04354743

AVIL advillin 1.533621 0.029517

C4orf23 chromosome 4 open reading frame 23 1.533607 0.04939469

CHPvD chordin 1.533076 0.00878228

SCN9A sodium channel, voltage-gated, type IX, alpha 1.532799 0.00567101 subunit

BACH2 BTB and CNC homology 1 , basic leucine zipper 1.53273 0.00813943 transcription factor 2

DISP1 dispatched homolog 1 (Drosophila) 1.532601 0.04747084

CACNA1 calcium channel, voltage-dependent, L type, alpha 1.532479 0.03917101

S IS subunit

NHEDC1 Na+/H+ exchanger domain containing 1 1.532385 0.04775145

EXOC3 exocyst complex component 3 1.53236 0.03192753

PH G2 phosphorylase kinase, gamma 2 (testis) 1.532241 0.03755378

LAPTM4 lysosomal protein transmembrane 4 beta 1.531927 0.01663365

B

SRPK2 SFRS protein kinase 2 1.531659 0.03108475 ClorflOl chromosome 1 open reading frame 101 1.531 197 0.03580263 MGC3340 #N/A 1.531067 0.03094266 7

CDH26 cadherin 26 1.530946 0.02848122

ATP6V0E ATPase, H+ transporting, lysosomal 9kDa, V0 1.530942 0.02829998

1 subunit el

CPNE3 copine III 1.530783 0.01178837

OCIAD2 #N/A 1.530762 0.03368961

ANKMY2 ankyrin repeat and MYND domain containing 2 1.530745 0.03959362

DGKZ diacylglycerol kinase, zeta 104kDa 1.530732 0.01213983

COX18 #N/A 1.530722 0.03748606

TRIM28 tripartite motif-containing 28 1.530532 0.03840176

ST7 suppression of tumorigenicity 7 1.530312 0.02388241

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

CNPY4 canopy 4 homolog (zebrafish) 1.530129 0.04723845 LSS lanosterol synthase (2,3-oxidosqualene-lanosterol 1.529869 0.02730441 cyclase)

MST02P misato homolog 2 pseudogene 1.529674 0.02938553

HRH2 #N/A 1.529572 0.02613059

DYNC1I2 dynein, cytoplasmic 1, intermediate chain 2 1.529406 0.03549435

PBX1 pre-B-cell leukemia homeobox 1 1.529339 0.00602163

WWOX WW domain containing oxidoreductase 1.529309 0.04842444

GTSE1 G-2 and S-phase expressed 1 1.529293 0.04317673

PRELID2 PPvELI domain containing 2 1.529074 0.04146019

PDLIM7 PDZ and LIM domain 7 (enigma) 1.528889 0.02434886

DONSON downstream neighbor of SON 1.528846 0.0376529

SNAPC4 small nuclear RNA activating complex, 1.528841 0.0292172 polypeptide 4, 190kDa

RASGRF2 Ras protein-specific guanine nucleotide-releasing 1.528519 0.02536069 factor 2

TBCCD 1 TBCC domain containing 1 1.528518 0.04802688

NMNAT1 nicotinamide nucleotide adenylyltransf erase 1 1.528446 0.02435834

GAGE2A #N/A 1.528331 0.00046436

XYLT1 xylosyltransf erase I 1.52831 0.02859266

ARL 15 ADP-ribosylation factor-like 15 1.528169 0.04972766

SLAMF6 SLAM family member 6 1.527986 0.03142929

BRWD3 bromodomain and WD repeat domain containing 3 1.527275 0.00310356 FLJ32065 Hypothetical protein FLJ32065 1.527232 0.03715658 EDEM1 ER degradation enhancer, mannosidase alpha-like 1.527109 0.009607

1

EFCAB4B #N/A 1.527087 0.03311729

MBOAT2 membrane bound O-acyltransferase domain 1.526811 0.04662587 containing 2

TP53TG3 #N/A 1.526577 0.01798109 RPGR retinitis pigmentosa GTPase regulator 1.526564 0.03311823 IVNS 1 AB influenza virus NS 1 A binding protein 1.526505 0.04656562 P

C3orfl Chromosome 3 open reading frame 1 1.526467 0.02580067 TCERGIL transcription elongation regulator 1-like 1.526411 0.03687745 RTEL1 regulator of telomere elongation helicase 1 1.526194 0.02923067 PIAS4 protein inhibitor of activated STAT, 4 1.526122 0.04829212 RRAGC Ras-related GTP binding C 1.525906 0.01474772 CIITA class II, major histocompatibility complex, 1.525854 0.04492051 transactivator

SCN2A sodium channel, voltage-gated, type II, alpha 1.5257 0.00243559 subunit

GALNT5 UDP-N-acetyl-alpha-D-galactosamine:polypeptide 1.525654 0.04313718

N-acetylgalactosaminyltransferase 5 (GalNAc-T5)

PCIF1 PDX1 C-terminal inhibiting factor 1 1.525599 0.01919144 SSX3 #N/A 1.525589 0.01438453 C 19orf61 chromosome 19 open reading frame 61 1.525428 0.02554083 SMEK1 SMEK homolog 1, suppressor of mekl 1.525278 0.02973042

(Dictyostelium)

AKAP4 #N/A 1.525002 0.02279171

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P

Symbol Change value

PELI2 pellino homolog 2 (Drosophila) 1.524603 0.00735412

HEATR1 HEAT repeat containing 1 1.524537 0.02752963

ARR3 arrestin 3, retinal (X-arrestin) 1.524478 0.0043137

UNC5C unc-5 homolog C (C. elegans) 1.524469 0.04499824

UGT2B15 #N/A 1.52436 0.02623177

SOX4 SRY (sex determining region Y)-box 4 1.524227 0.00886675

TTLL3 tubulin tyrosine ligase-like family, member 3 1.5241 11 0.00736764

FLT3LG fms-related tyrosine kinase 3 ligand 1.524077 0.01175394

SSH1 slingshot homolog 1 (Drosophila) 1.523977 0.04184018

VIM vimentin 1.523884 0.04124592

PODXL podocalyxin-like 1.523804 0.00861833

ZNF436 zinc finger protein 436 1.523707 0.04067693

ZNF433 zinc finger protein 433 1.523594 0.01444774

PPARGC1 peroxisome proliferator-activated receptor gamma, 1.523461 0.01858888

B coactivator 1 beta

COL9A1 collagen, type IX, alpha 1 1.523327 8.24E-05

PLCE1 phospholipase C, epsilon 1 1.523254 0.0115958

DNAJC4 DnaJ (Hsp40) homolog, subfamily C, member 4 1.523192 0.03186698

ZNF286A zinc finger protein 286A 1.522884 0.03164334

ANKRD2 ankyrin repeat domain 28 1.522866 0.0295649

8

C7orf42 chromosome 7 open reading frame 42 1.522728 0.04504565 TAF2 TAF2 RNA polymerase II, TATA box binding 1.522666 0.04512762 protein (TBP)-associated factor, 150kDa

TSC22D2 TSC22 domain family, member 2 1.522282 0.0030166

C4A complement component 4A (Rodgers blood group) 1.522279 0.04317567

RYR1 ryanodine receptor 1 (skeletal) 1.522278 0.0461507

RBPMS2 RNA binding protein with multiple splicing 2 1.522198 0.01969139

TGIF1 TGFB-induced factor homeobox 1 1.522064 0.01450587

AHSA2 AHA1, activator of heat shock 90kDa protein 1.522001 0.04031996

ATPase homolog 2 (yeast)

SCN3A sodium channel, voltage-gated, type III, alpha 1.521923 0.02607254 subunit

LIMD1 LIM domains containing 1 1.521911 0.04640935

ZMYND1 #N/A 1.521834 0.02496381

2

ITGA10 integrin, alpha 10 1.521524 0.00959363

HEXA hexosaminidase A (alpha polypeptide) 1.521441 0.03564508

ST8SIA4 ST8 alpha-N-acetyl-neuraminide alpha-2,8- 1.521432 0.01744928 sialyltransferase 4

CAV1 caveolin l. caveolae protein, 22kDa 1.521415 0.03791804

ALDH7A aldehyde dehydrogenase 7 family, member Al 1.521211 0.04933379

1

BEST3 bestrophin 3 1.521204 0.0388346 CACNB2 calcium channel, voltage-dependent, beta 2 1.521042 0.00676234 subunit

TGM1 #N/A 1.521018 0.03581708 ARMC6 armadillo repeat containing 6 1.520888 0.02893813 AD API ArfGAP with dual PH domains 1 1.520758 0.0364661 KCNK10 #N/A 1.520752 0.04920474

DBi; 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

CLASP2 #N/A 1.520681 0.04356009 TN I3 troponin I type 3 (cardiac) 1.520515 0.03944469 EIF4ENIF eukaryotic translation initiation factor 4E nuclear 1.520404 0.00348984 1 import factor 1

ZNF615 zinc finger protein 615 1.520245 0.02108454 FLT3 fms-related tyrosine kinase 3 1.520185 0.01322775 A2ML1 #N/A 1.519952 0.00890104 CR1 complement component (3b/4b) receptor 1 (Knops 1.519948 0.0278393 blood group)

EVC2 Ellis van Creveld syndrome 2 1.519929 0.02167464

IGHM #N/A 1.519861 0.04848814

DEPDC4 DEP domain containing 4 1.519762 0.03247166

HVCN1 hydrogen voltage-gated channel 1 1.51976 0.02238518

HSPB1 heat shock 27kDa protein 1 1.519678 0.02359025

RGS6 regulator of G-protein signaling 6 1.519587 0.04840437

AKD2 #N/A 1.519497 0.01294726

RIN3 Ras and Rab interactor 3 1.519438 0.03060739

IMPG2 Interphotoreceptor matrix proteoglycan 2 1.518982 0.01469147

SEPSECS Sep (O-phosphoserine) tRNA:Sec (selenocysteme) 1.518354 0.02087681 tRNA synthase

RGS7 regulator of G-protein signaling 7 1.518207 0.01586147 ZNF778 zinc finger protein 778 1.518154 0.01480456 OPRM1 opioid receptor, mu 1 1.518105 0.00314228 DOCK 10 dedicator of cytokinesis 10 1.518044 0.02778568 KIN KIN, antigenic determinant of recA protein 1.517916 0.03923584 homolog (mouse)

ZNF507 zinc finger protein 507 1.51731 0.00611545

TBC1D3 TBC1 domain family, member 3 1.517061 0.03974991

APOC2 #N/A 1.516825 0.03157728

GRAMD1 GRAM domain containing 1C 1.516205 0.04967244

C

PROCR protein C receptor, endothelial 1.516129 0.01491359

C3AR1 complement component 3 a receptor 1 1.515918 0.01581163

PDE4DIP phosphodiesterase 4D interacting protein 1.515754 0.01390453

CLEC1 1A #N/A 1.515747 0.0440781

KIAA171 KIAA1712 1.515593 0.04527365

2

PRY PTPN13-like, Y-linked 1.515345 0.01405544

PTGFR #N/A 1.515272 0.01227869

MLL2 myeloid/lymphoid or mixed-lineage leukemia 2 1.515093 0.01956442

EEF1A1 eukaryotic translation elongation factor 1 alpha 1 1.51498 0.0095039

SLC25A1 solute carrier family 25 (mitochondrial carrier; 1.514693 0.04630693

0 dicarboxylate transporter), member 10

MCOLN2 mucolipin 2 1.51452 0.04997968

Clorfl98 chromosome 1 open reading frame 198 1.514489 0.00459002

FAM176A family with sequence similarity 176, member A 1.514341 0.04276084

CBS #N/A 1.5142 0.04132355

MYST4 MYST histone acetyltransferase (monocytic 1.51419 0.04610093 leukemia) 4

EML5 echinoderm microtubule associated protein like 5 1.514188 0.01607303

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

SPG7 spastic paraplegia 7 (pure and complicated 1.51408 0.0262147 autosomal recessive)

METTL7 #N/A 1.514022 0.01042424 B

COL11A1 collagen, type XI, alpha 1 1.514014 0.00257131

PPFIBP2 #N/A 1.513922 0.01840277 TRPA1 transient receptor potential cation channel, 1.513861 0.01788238 subfamily A, member 1

OR5P3 #N/A 1.513725 0.02916868

NEK1 NIMA (never in mitosis gene a)-related kinase 1 1.513498 0.00670321

ABCA13 ATP-binding cassette, sub-family A (ABC1), 1.513479 0.02456736 member 13

ZNF3970 #N/A 1.513279 0.00197526 S

TAF4 TAF4 RNA polymerase II, TATA box binding 1.513223 0.03373199 protein (TBP)-associated factor, 135kDa

AGPAT6 #N/A 1.512954 0.03524408 SLC25A4 solute carrier family 25, member 45 1.512932 0.01025411 5

TDRD7 tudor domain containing 7 1.512892 0.03268637

C8orf46 chromosome 8 open reading frame 46 1.512723 0.03182585

PHF20 PHD finger protein 20 1.512697 0.02352271

PEF1 #N/A 1.51265 0.00099369

KLK2 kallikrein-related peptidase 2 1.512505 0.01798366

CYP2C8 #N/A 1.512442 0.03768932

RAPGEF2 Rap guanine nucleotide exchange factor (GEF) 2 1.512434 0.02678822

MRVI1 murine retrovirus integration site 1 homolog 1.512119 0.02275801

KCNMA1 potassium large conductance calcium-activated 1.512118 0.02490189 channel, subfamily M, alpha member 1

RFC4 replication factor C (activator 1) 4, 37kDa 1.51195 0.00433235

TES 2 #N/A 1.511917 0.03606908

TIAM2 T-cell lymphoma invasion and metastasis 2 1.511809 0.00026137

LAMA5 laminin, alpha 5 1.51 1632 0.02817024

ERAP1 #N/A 1.511626 0.02847767

CHN1 chimerin (chimaerin) 1 1.511498 0.03848462

TEX261 testis expressed 261 1.511333 0.04895197

EFNB2 ephrin-B2 1.511313 0.0281 1974

HSF2 heat shock transcription factor 2 1.511271 0.02081911

BLOC1 S2 biogenesis of lysosomal organelles complex- 1, 1.511216 0.02923129 subunit 2

C1QL2 complement component 1, q subcomponent-like 2 1.511113 0.0491 1363

THUMPD THUMP domain containing 3 1.510729 0.03991285

3

NUMA1 nuclear mitotic apparatus protein 1 1.510652 0.02466567 MAP4K1 mitogen-activated protein kinase kinase kinase 1.510576 0.01999283 kinase 1

GRAMD3 GRAM domain containing 3 1.510198 0.03505043 PET1 12L #N/A 1.509642 0.03583531 GSTTP1 glutathione S-transferase theta pseudogene 1 1.509243 0.01952154 ZNF18 zinc finger protein 18 1.509015 0.01040435

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

TNNI1 troponin I type 1 (skeletal, slow) 1.508775 0.02128511

NSAP1 1 nervous system abundant protein 11 1.508701 0.02008257

LARP6 #N/A 1.50845 0.0051241

DDB2 damage-specific DNA binding protein 2, 48kDa 1.50842 0.04650229

PGM3 phosphoglucomutase 3 1.508225 0.01688132

CCDC135 coiled-coil domain containing 135 1.50795 0.02160831

CARD 11 caspase recruitment domain family, member 11 1.507431 0.03283898

ACOT13 acyl-CoA thioesterase 13 1.507239 0.0425116

LPHN3 latrophilin 3 1.50705 0.01904418

IQCE IQ motif containing E 1.506926 0.03294537

NLRP6 #N/A 1.506865 0.00737172

WWC2 WW and C2 domain containing 2 1.506714 0.02348157

EIF4EBP3 #N/A 1.506626 0.00694641 hCG_2431 #N/A 1.506625 0.00885811

2

ZBTB11 zinc finger and BTB domain containing 11 1.506409 0.02793328 SFRS15 splicing factor, arginine/serine-rich 15 1.506266 0.01961157 ZNF354B zinc finger protein 354B 1.50625 0.02066909 RASGRP3 RAS guanyl releasing protein 3 (calcium and 1.506213 0.00673812

DAG-regulated)

RIC8A resistance to inhibitors of cholinesterase 8 1.506025 0.04323676 homolog A (C. elegans)

CD226 #N/A 1.505998 0.04475406 PPM1L protein phosphatase, Mg2+/Mn2+ dependent, 1L 1.505912 0.04544897 LNPEP leucyl/cystinyl aminopeptidase 1.505637 0.04502002 CLASP 1 cytoplasmic linker associated protein 1 1.505522 0.02046148 SMPD2 sphingomyelin phosphodiesterase 2, neutral 1.505414 0.04020793 membrane (neutral sphingomyelinase)

CREB3L3 #N/A 1.505349 0.03244781

MEMOl Mediator of cell motility 1 1.505264 0.0182921

NCR3 natural cytotoxicity triggering receptor 3 1.505256 0.00048627

DEN D1 DENN/MADD domain containing 1C 1.505248 0.03090044

C

C5orf24 chromosome 5 open reading frame 24 1.505156 0.04864502 ELM03 engulfment and cell motility 3 1.505156 0.01966598 LRRC37A leucine rich repeat containing 37, member A4 1.504995 0.04713156 4 (pseudogene)

TMEM8 Transmembrane protein 8 (five membrane- 1.504856 0.01099229 spanning domains)

GABRD gamma-aminobutyric acid (GABA) A receptor, 1.504786 0.00463672 delta

CPA3 carboxypeptidase A3 (mast cell) 1.504658 0.04232725

BAT4 HLA-B associated transcript 4 1.504622 0.04859982

TKT transketolase 1.504378 0.04523652

APOM apolipoprotein M 1.503803 0.0393742

BIRC3 #N/A 1.503709 0.00258758

USP40 ubiquitin specific peptidase 40 1.503395 0.00413796

CD86 #N/A 1.503289 0.03540023

IL27 #N/A 1.503053 0.04791632

C9orfl71 #N/A 1.502746 0.03462208

DBl/ 09437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

RSBN1 round spermatid basic protein 1 1.502467 0.01937463

COBL cordon-bleu homolog (mouse) 1.502347 0.02524997

ITGAL integrin, alpha L (antigen CD11 A ( i 80), 1.502314 0.00920043 lymphocyte function-associated antigen 1 ; alpha

polypeptide)

PLS 1 plastin 1 1.502107 0.03009453 DAAM2 dishevelled associated activator of morphogenesis 1.501909 0.02196621

2

ZNF595 zinc finger protein 595 1.501845 0.03326776

LAMB2 laminin, beta 2 (laminin S) 1.501796 0.0297375

LUZP6 leucine zipper protein 6 1.501732 0.03627483

ODF2L outer dense fiber of sperm tails 2-like 1.501589 0.02970323

TEKT1 tektin 1 1.501499 0.0160542

ZSCAN5 zinc finger and SCAN domain containing 5A 1.501432 0.01523309

A

DNAI1 dynein, axonemal, intermediate chain 1 1.501239 0.02589567

WDR72 WD repeat domain 72 1.501077 0.03810376

PRKD3 protein kinase D3 1.500973 0.04375189

GGT7 gamma-glutamyltransferase 7 1.500897 0.0300489

PRSS1 #N/A 1.500792 0.00210628

EPC1 enhancer of polycomb homolog 1 (Drosophila) 1.500699 0.03620974 LK12 kallikrein-related peptidase 12 1.500604 0.04722164

OR5K1 #N/A 1.500599 0.01846902

PCDHGA #N/A 1.500514 0.01932019

2

CREM cAMP responsive element modulator 1.500393 0.01481585

GPR177 G protein-coupled receptor 177 1.500203 0.04882108

IL16 interleukin 16 (lymphocyte chemoattractant factor) 1.499957 3.09E-06

ATP13A4 ATPase type 13A4 1.499852 0.02048198

RNF125 #N/A 1.499719 0.02868188

WDR78 WD repeat domain 78 1.499613 0.03715928

TSHZ2 #N/A 1.499495 0.03449735

MUM1L1 melanoma associated antigen (mutated) 1 -like 1 1.499362 0.02683646

Clorf97 #N/A 1.499283 0.00436052

LOXL2 lysyl oxidase-like 2 1.499279 0.00303413

C1GALT1 core 1 synthase, glycoprotein-N- 1.499215 0.03790968 acetylgalactosamine 3-beta-galactosyltransferase,

1

SLC44A1 solute carrier family 44, member 1 1.499123 0.00699643 DDX3X DEAD (Asp-Glu- Ala-Asp) box polypeptide 3, X- 1.498945 0.00547769 linked

HAUS6 HAUS augmin-like complex, subunit 6 1.498882 0.02557891

ClOorflO #N/A 1.498872 0.01613471

TBC1D3B #N/A 1.498802 0.01035539

CCDC93 coiled-coil domain containing 93 1.498678 0.02519198

ACOX3 acyl-CoA oxidase 3, pristanoyl 1.498653 0.01323784

HSPBAP1 HSPB (heat shock 27kDa) associated protein 1 1.498525 0.03297875

SLC30A6 solute carrier family 30 (zinc transporter), member 1.498497 0.03691582

6

TEX13B testis expressed 13B 1.498463 0.04611241

DB1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upreguiated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

PAMR1 peptidase domain containing associated with 1.498358 0.03428594 muscle regeneration 1

ARHGEF Rho guanine nucleotide exchange factor (GEF) 17 1.498327 0.02393166 17

ZBP1 Z-DNA binding protein 1 1.498245 0.01453906 ABCA11P ATP -binding cassette, sub-family A (ABC1), 1.498181 0.04124259 member 11 (pseudogene)

ENAH enabled homolog (Drosophila) 1.498006 0.01643479

C10orf99 #N/A 1.497989 0.04485341

DNAJC10 DnaJ (Hsp40) homolog, subfamily C, member 10 1.497865 0.03664069

MAP3K9 mitogen-activated protein kinase kinase kinase 9 1.497852 0.04433363

MYLK3 myosin light chain kinase 3 1.497596 0.03993566

EXOl exonuclease 1 1.497513 0.01883602

UBQLN2 ubiquilin 2 1.497031 0.04532667

KATNB1 katanin p80 (WD repeat containing) subunit B 1 1.496953 0.02780858

ADAM11 ADAM metallopeptidase domain 11 1.496387 0.00656196

KANK2 KN motif and ankyrin repeat domains 2 1.496305 0.04455511

BID BH3 interacting domain death agonist 1.496027 0.04501775

SMAD1 SMAD family member 1 1.495787 0.01473042

ADAMTS ADAMTS-like 5 1.495476 0.03975532

L5

TBC1D20 #N/A 1.495357 0.03391408

PIGR #N/A 1.495263 0.037885

MAP3K3 mitogen-activated protein kinase kinase kinase 3 1.495253 0.01286347

PDZK1P1 PDZ domain containing 1 pseudogene 1 1.495225 0.04915917

HEATR6 HEAT repeat containing 6 1.495068 0.00184054

ZNF136 zinc finger protein 136 1.494622 0.03399777

DAAM1 dishevelled associated activator of morphogenesis 1.494444 0.00094922

1

TNFRSF9 tumor necrosis factor receptor superfamily, 1.494407 0.04184248 member 9

GPX6 Glutathione peroxidase 6 (olfactory) 1.494389 0.00809537 NSUN5 NOP2/Sun domain family, member 5 1.494193 0.017034 ING3 inhibitor of growth family, member 3 1.493899 0.0089448 ABCA9 ATP -binding cassette, sub-family A (ABC1), 1.493891 0.04695243 member 9

WR Werner syndrome, RecQ helicase-like 1.493874 0.04009878

PLXNB1 plexin Bl 1.493586 0.04305745

RIT1 Ras-like without CAAX 1 1.493381 0.00705308

C9orfl25 chromosome 9 open reading frame 125 1.493371 0.02103353

DCBLD1 discoidin, CUB and LCCL domain containing 1 1.492919 0.0084101 1

EIF3B eukaryotic translation initiation factor 3, subunit B 1.492839 0.00826051

HSPG2 heparan sulfate proteoglycan 2 1.492714 0.02841941

POLR2B polymerase (RNA) II (DNA directed) polypeptide 1.492545 0.0174615

B, 140kDa

UNC93B1 unc-93 homolog B 1 (C. elegans) 1.492491 0.0071786

SPACA1 #N/A 1.492342 0.01694002

ADAT2 adenosine deaminase, tRNA-specific 2, TAD2 1.492002 0.00662497 homolog (S. cerevisiae)

ST7L suppression of tumorigenicity 7 like 1.491995 0.03027795

DB1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

SLC30A4 solute carrier family 30 (zinc transporter), member 1.491871 0.02964738

4

CEP 170 centrosomal protein 170kDa 1.491814 0.03664036

C6orfl l8 Chromosome 6 open reading frame 118 1.491666 0.02077073

DNASE1 deoxyribonuclease I-like 2 1.491477 0.02179018

L2

GCA grancalcin, EF-hand calcium binding protein 1.491456 0.04370834

CYP2R1 Cytochrome P450, family 2, subfamily R, 1.491451 0.02409106 polypeptide 1

CNTLN centlein, centrosomal protein 1.491392 0.01117339 SRMS src-related kinase lacking C-terminal regulatory 1.491372 0.01927997 tyrosine and N-terminal myristylation sites

HOOK3 hook homolog 3 (Drosophila) 1.491337 0.01026371 NPHP3 nephronophthisis 3 (adolescent) 1.491291 0.01239694 MTA1 metastasis associated 1 1.49122 0.03802427 ELAVL3 ELAV (embryonic lethal, abnormal vision, 1.491151 0.0469912

Drosophila)-like 3 (Hu antigen C)

RAD52 RAD 52 homolog (S. cerevisiae) 1.491061 0.03958894

SEC31B SEC31 homolog B (S. cerevisiae) 1.490681 0.01933014

UGT3A1 UDP glycosyltransferase 3 family, polypeptide Al 1.490658 0.03668628

Clorfl23 chromosome 1 open reading frame 123 1.490522 0.04120738

MLL3 myeloid/lymphoid or mixed-lineage leukemia 3 1.490522 0.04072548

KIR2DS2 #N/A 1.490465 0.00909117

PRDM10 PR domain containing 10 1.490369 0.03714741

TUBA4A tubulin, alpha 4a 1.489974 0.01531328

TRIM 15 tripartite motif-containing 15 1.489745 0.02704514

DEN D1 DENN/MADD domain containing IB 1.489693 0.03803935

B

PDE11A phosphodiesterase 11A 1.489508 0.01033018 HIVEP2 human immunodeficiency virus type I enhancer 1.489475 0.01296614 binding protein 2

CPSF1 cleavage and polyadenylation specific factor 1, 1.489363 0.01453211

160kDa

GCOM1 GRTNLIA complex locus 1.489269 0.03293698 SLC18A2 solute carrier family 18 (vesicular monoamine), 1.489234 0.01707352 member 2

SNAP91 #N/A 1.489193 0.00852122

B3GNT8 #N/A 1.488864 0.01925139

VPRBP Vpr (HIV-1) binding protein 1.48869 0.04377584

PSD3 pleckstrin and Sec7 domain containing 3 1.488596 0.01387586

SP2 Sp2 transcription factor 1.488555 0.00776772

MKS1 Meckel syndrome, type 1 1.488428 0.04044232

MAGEA2 melanoma antigen family A, 2 1.487961 0.02809906

CSRPl cysteine and glycine-rich protein 1 1.487678 0.01194748

METTL3 methyltransferase like 3 1.487554 0.03923316

FLJ25006 #N/A 1.487515 0.03409879

DOCK4 dedicator of cytokinesis 4 1.487201 0.04840538

TCHH trichohyalin 1.487154 0.03428957

MRPL37 mitochondrial ribosomal protein L37 1.487072 0.02957386

ITSN1 intersectin 1 (SH3 domain protein) 1.487022 0.0462667

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

SNX9 sorting nexin 9 1.486758 0.01594801

EIF2C3 eukaryotic translation initiation factor 2C, 3 1.486683 0.0173166

TCN2 transcobalamin II 1.486551 0.02764432

GALK2 galactokinase 2 1.486521 0.02855803

TTC8 #N/A 1.486322 0.00425549

PADI3 peptidyl arginine deiminase, type III 1.486121 0.03493482

MFAP3 microfibrillar-associated protein 3 1.486056 0.01292446

NAALAD #N/A 1.486029 0.03891559 LI

PGCP plasma glutamate carboxypeptidase 1.485871 0.00774448

CXXC1 CXXC finger 1 (PHD domain) 1.485842 0.02022819

IFNGR1 interferon gamma receptor 1 1.485695 0.03541863

ADRA1A adrenergic, alpha- 1A-, receptor 1.485596 0.03294264

NBEAL2 neurobeachin-like 2 1.485448 0.03417637

ZNF285A #N/A 1.485359 0.04852051

MTHFS 5,10-methenyltetrahydrofolate synthetase (5- 1.485152 0.03172732 formyltetrahydrofolate cyclo-ligase)

INTS12 integrator complex subunit 12 1.485117 0.04854864

TSGA10 testis specific, 10 1.485017 0.01942415

AGXT2L1 #N/A 1.484978 0.04359196

VAMP5 #N/A 1.48482 0.02867714

XPR1 xenotropic and polytropic retrovirus receptor 1 1.484626 0.045761 18

FLJ43879 FLJ43879 protein 1.484599 0.01941404

LDHB lactate dehydrogenase B 1.484571 0.01769543

OTOF otoferlin 1.484425 0.00548029

WDR8 WD repeat domain 8 1.484219 0.0073097

CCBL2 cysteine conjugate-beta lyase 2 1.484133 0.04898507

GLIPR2 #N/A 1.483972 0.00476043

FOXK2 forkhead box 2 1.483924 0.0323877

CCDC25 coiled-coil domain containing 25 1.483805 0.01005576

MTTP microsomal triglyceride transfer protein 1.48369 0.02387116

PLEKHA pleckstrin homology domain containing, family A 1.483463 0.0218927

7 member 7

MDM1 Mdm4, transformed 3T3 cell double minute l, p53 1.483439 0.02488512 binding protein (mouse)

CYP51A1 cytochrome P450, family 51, subfamily A, 1.483035 0.00605888 polypeptide 1

C12orf37 chromosome 12 open reading frame 37 1.483014 0.0199483

FTCD formiminotransferase cyclodeaminase 1.482859 0.03637955

C8orf68 #N/A 1.482849 0.02731009

NFATC2I nuclear factor of activated T-cells, cytoplasmic, 1.482615 0.03403372

P calcineurin-dependent 2 interacting protein

BMPER BMP binding endothelial regulator 1.48251 0.01666766

UGT2B17 UDP glucuronosyltransferase 2 family, 1.482313 0.04353663 polypeptide B17

XRN2 5'-3' exoribonuclease 2 1.482291 0.03334524

6-Mar #N/A 1.482159 0.00620696

ZNF777 zinc finger protein 777 1.481987 0.01421451

SAP30BP SAP30 binding protein 1.481963 0.02114436

CACNA1 calcium channel, voltage-dependent, P/Q type, 1.480764 0.0107704

DB1/ 694₃7516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

A alpha 1A subunit

POLR3B polymerase (RNA) III (DNA directed) polypeptide 1.480662 0.0463736

B

UBE2D4 #N/A 1.480249 0.01448582

GRM5 glutamate receptor, metabotropic 5 1.480165 0.02136922

MTFR1 mitochondrial fission regulator 1 1.480156 0.01636382

CLDND2 claudin domain containing 2 1.480138 0.03516792

OTUB1 #N/A 1.479936 0.01364523

RBBP6 retinoblastoma binding protein 6 1.479665 0.04940251

MED20 mediator complex subunit 20 1.479368 0.0142524

ANKRD4 ankyrin repeat domain 44 1.478832 0.02380591

4

CREB3L2 cAMP responsive element binding protein 3 -like 2 1.478797 0.02076942

ADCY6 adenylate cyclase 6 1.478713 0.01974027

DCI dodecenoyl-CoA isomerase 1.478667 0.03647473

FLJ23834 Hypothetical protein FLJ23834 1.478424 0.04820602 ZKSCAN zinc finger with KRAB and SCAN domains 5 1.478392 0.03120821 5

FBX08 F-box protein 8 1.478277 0.03152013 LAMC2 laminin, gamma 2 1.478091 0.04729644 ANKRD5 #N/A 1.477698 0.00101494 4

MINK1 misshapen-like kinase 1 (zebrafish) 1.47757 0.01754182

NXN nucleoredoxin 1.477182 0.02929918

FASTKD3 FAST kinase domains 3 1.477163 0.0107589

SH3GLB2 SH3 -domain GRB2-like endophilin B2 1.477091 0.03236397

CCDC81 coiled-coil domain containing 81 1.477054 0.01975538

PELI1 pellino homolog 1 (Drosophila) 1.47698 0.03398163

DOCK2 dedicator of cytokinesis 2 1.476523 0.02244916

WISP1 #N/A 1.47606 0.01719529

BGLAP #N/A 1.476055 0.00738682

KLHDC6 Kelch domain containing 6 1.476055 0.03928562

ATM ataxia telangiectasia mutated 1.476006 0.04252303

PTPRT protein tyrosine phosphatase, receptor type, T 1.475416 0.02958476

OR2T11 Olfactory receptor, family 2, subfamily T, member 1.475392 0.00841785

11

FANCL Fanconi anemia, complementation group L 1.475368 0.03468102

GRB14 growth factor receptor-bound protein 14 1.475083 0.03764759

TCF15 transcription factor 15 (basic helix-loop-helix) 1.474894 0.00719009

TGFBR2 #N/A 1.474842 0.03290676

C2orf28 chromosome 2 open reading frame 28 1.474813 0.01733917

CUBN cubilin (intrinsic factor-cobalamin receptor) 1.474557 0.04055775

COQ2 coenzyme Q2 homolog, prenyltransferase (yeast) 1.474367 0.02612499

LTBP4 latent transforming growth factor beta binding 1.474245 0.00585024 protein 4

LIG1 ligase I, DNA, ATP-dependent 1.474139 0.00096638 ACAP2 ArfGAP with coiled-coil, ankyrin repeat and PH 1.474102 0.04857355 domains 2

ABCG1 ATP-binding cassette, sub-family G (WHITE), 1.473995 0.03561249 member 1

DB1/ 694₃7516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P

Symbol Change value

USH1G #N/A 1.473589 0.04293844

CXXC4 #N/A 1.473497 0.04456624

MAT2A methionine adenosyltransferase II, alpha 1.473436 0.00549543

Clorf96 chromosome 1 open reading frame 96 1.473276 0.00325284

SLC4A3 solute carrier family 4, anion exchanger, member 3 1.472698 0.01015349

VWCE von Willebrand factor C and EGF domains 1.472335 0.02063716

MAPK10 mitogen-activated protein kinase 10 1.472218 0.04166794

FAM151B family with sequence similarity 151, member B 1.471846 0.03385216

NEB nebulin 1.471836 0.0064173

SAG S-antigen; retina and pineal gland (arrestin) 1.471714 0.02154346

ABCG5 ATP-binding cassette, sub-family G (WHITE), 1.471531 0.03879777 member 5

CDK3 cyclin-dependent kinase 3 1.471323 0.0023621 1

TNS4 tensin 4 1.47103 0.04334127

HBP1 HMG-box transcription factor 1 1.470971 0.0181465

IL20 interleukin 20 1.470955 0.03946544

ZNF335 zinc finger protein 335 1.470915 0.01884214

SNX31 sorting nexin 31 1.470781 0.04653324

CCDC19 coiled-coil domain containing 19 1.470698 0.01932886

DZIP3 DAZ interacting protein 3, zinc finger 1.470608 0.04900261

ASXL1 additional sex combs like 1 (Drosophila) 1.470256 0.00998521

CYTH2 cytohesin 2 1.470054 0.01718416

FAM12A #N/A 1.469785 0.01492526

KCNG3 potassium voltage-gated channel, subfamily G, 1.46964 0.0456643 member 3

MRPS9 mitochondrial ribosomal protein S9 1.469423 0.03660104

FLNC filamin C, gamma 1.469361 0.04022687

SORL1 sortilin-related receptor, L(DLR class) A repeats- 1.469308 0.03912596 containing

C15orf44 chromosome 15 open reading frame 44 1.469079 0.00230053

ZCCHC9 zinc finger, CCHC domain containing 9 1.46906 0.04658745

USP33 ubiquitin specific peptidase 33 1.468906 0.04743185

GP2 glycoprotein 2 (zymogen granule membrane) 1.468867 0.04707864

MFN1 mitofusin 1 1.468406 0.0499737

RCOR2 REST corepressor 2 1.46834 0.04187092

ZCCHC4 #N/A 1.467774 0.039209

CAPRIN2 caprin family member 2 1.46771 1 0.0334225

NELF nasal embryonic LHRH factor 1.467618 0.04955878

Clorf51 chromosome 1 open reading frame 51 1.467414 0.0324553

RNF216 ring finger protein 216 1.467405 0.03527836

C19orf28 chromosome 19 open reading frame 28 1.467382 0.00690267

TBCE tubulin folding cofactor E 1.467239 0.02970097

SH3GL3 SH3 -domain GRB2-like 3 1.467149 0.00864535

PRICKLE prickle homolog 1 (Drosophila) 1.467122 0.03166895

1 1

MLLT4 myeloid/lymphoid or mixed-lineage leukemia 1.467081 0.04155191

(trithorax homolog, Drosophila); translocated to, 4

PNPT1 polyribonucleotide nucleotidyltransferase 1 1.466973 0.0270214

NFKB1 nuclear factor of kappa light polypeptide gene 1.466917 0.00255794 enhancer in B-cells 1

DB)/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

VLDLR very low density lipoprotein receptor 1.46686 0.02591145 XPNPEP2 X-prolyl aminopeptidase (aminopeptidase P) 2, 1.466623 0.02326367 membrane-bound

ITPR3 inositol 1,4,5-triphosphate receptor, type 3 1.466453 0.0144499

KIAA092 KIAA0922 1.46645 0.03511673

2

FAM159A family with sequence similarity 159, member A 1.466374 0.04524545 ABCA10 ATP -binding cassette, sub-family A (ABC1), 1.466138 0.00512099 member 10

MRC1 mannose receptor, C type 1 1.466136 0.01757616

TUBGCP tubulin, gamma complex associated protein 5 1.466 0.00886803

5

TMED6 transmembrane emp24 protein transport domain 1.465865 0.03807474 containing 6

BTAF1 BTAF1 RNA polymerase II, B-TFIID 1.46569 0.00731777 transcription factor-associated, 170kDa (Motl

homolog, S. cerevisiae)

PRG4 Proteoglycan 4 1.465684 0.02402568 SPTY2D1 SPT2, Suppressor of Ty, domain containing 1 (S. 1.465459 0.02139714 cerevisiae)

NOL8 nucleolar protein 8 1.465276 0.02289714

ZNF713 zinc finger protein 713 1.46 106 0.00024057

GABRG2 gamma-aminobutyric acid (GAB A) A receptor, 1.464692 0.02878727 gamma 2

PPIL1 Peptidylprolyl isomerase (cyclophilin)-like 1 1.464672 0.01141798

RXFP4 #N/A 1.46451 0.03271493

SLC30A9 solute carrier family 30 (zinc transporter), member 1.464446 0.01606995

9

A2BP1 #N/A 1.464208 0.01074849

RNF168 ring finger protein 168 1.463842 0.01556207

LARS Leucyl-tRNA synthetase 1.46382 0.02711871

AMBRA1 autophagy/beclin-1 regulator 1 1.463678 0.03422866

TUSC3 tumor suppressor candidate 3 1.463532 0.01290509

KLF11 Kruppel-like factor 11 1.463417 0.03410459

ZNF213 zinc finger protein 213 1.463007 0.01143018 RT34 keratin 34 1.462809 0.04490343

RREB1 ras responsive element binding protein 1 1.462738 0.0215814

QRICH1 glutamine-rich 1 1.462606 0.03381265

SLC41A3 solute carrier family 41, member 3 1.462121 0.04905545

PPID peptidylprolyl isomerase D 1.461711 0.01995451

BRD7 bromodomain containing 7 1.461608 0.03610551

RYK RYK receptor-like tyrosine kinase 1.461366 0.03625633

RMND1 required for meiotic nuclear division 1 homolog 1.461224 0.00067929

(S. cerevisiae)

BNIP3L BCL2/adenovirus EIB 19kDa interacting protein 1.460959 0.03837602

3-like

NIT2 nitrilase family, member 2 1.460132 0.00731216 AHR aryl hydrocarbon receptor 1.460095 0.01824016 CREG2 cellular repressor of ElA-stimulated genes 2 1.460072 0.04688752 FARS2 phenylalanyl-tRNA synthetase 2, mitochondrial 1.460055 0.01449362

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

SLC22A8 solute carrier family 22 (organic anion 1.459997 0.04565017 transporter), member 8

AVPR1A #N/A 1.459881 0.01213536

RDH16 retinol dehydrogenase 16 (all-trans) 1.459701 0.01459158

FOSL2 FOS-like antigen 2 1.459671 0.02789882

CCDC84 coiled-coil domain containing 84 1.459194 0.01551605

C15orf26 chromosome 15 open reading frame 26 1.459144 0.01284189

RNF31 ring finger protein 31 1.458904 0.01875917

KIFAP3 kinesin-associated protein 3 1.458765 0.04901628

PvAETlE retinoic acid early transcript IE 1.458688 0.01521063

NFIX nuclear factor I X (CCAAT-binding transcription 1.458648 0.02610177 factor)

RRAGD #N/A 1.458582 0.03391708

C2orf37 Chromosome 2 open reading frame 37 1.458512 0.02153276

INE1 #N/A 1.458407 0.04987065

DSN1 DSN1, MIND kinetochore complex component, 1.458314 0.02872824 homo log (S. cerevisiae)

CPNE1 copine I 1.458259 0.04343134

FOXJ1 forkhead bo Jl 1.45819 0.04892679 KIAA010 #N/A 1.458123 0.01110807 0

NAV3 neuron navigator 3 1.457858 0.03630539

ZNF419 Zinc finger protein 419 1.457487 0.03637576

GPR144 G protein-coupled receptor 144 1.457421 0.0018568

SPTBN5 spectrin, beta, non-erythrocytic 5 1.457323 0.04072569

SLC1A3 solute carrier family 1 (glial high affinity 1.457036 0.00763698 glutamate transporter), member 3

SALL2 sal-like 2 (Drosophila) 1.456788 0.04573085

DLEC1 deleted in lung and esophageal cancer 1 1.456051 0.04460107

MYH3 myosin, heavy chain 3, skeletal muscle, embryonic 1.455842 0.04143603

MAGED4 melanoma antigen family D, 4 1.455781 0.04963849

FAM62C Family with sequence similarity 62 (C2 domain 1.455718 0.00153762 containing), member C

C14orf93 chromosome 14 open reading frame 93 1.455704 0.04065932

ALPK3 alpha-kinase 3 1.455636 0.02254821 TWF2 #N/A 1.455423 0.04305335

TPST1 tyrosylprotein sulfotransferase 1 1.455182 0.04488994

TRIM27 tripartite motif-containing 27 1.455008 0.00254227

AOC3 amine oxidase, copper containing 3 (vascular 1.45493 0.00124869 adhesion protein 1)

OR7C1 #N/A 1.454841 0.0273752

NR3C1 nuclear receptor subfamily 3, group C, member 1 1.454641 0.02746148

(glucocorticoid receptor)

C2orf86 chromosome 2 open reading frame 86 1.454464 0.03587193

MSLN mesothelin 1.454281 0.01815451

COL6A1 collagen, type VI, alpha 1 1.454271 0.04064534 HDHD1A #N/A 1.454111 0.01603581

HARS histidyl-tRNA synthetase 1.454047 0.02411035

PXK PX domain containing serine/threonine kinase 1.453734 0.02937152

GCLC glutamate-cysteine ligase, catalytic subunit 1.453663 0.02641978

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

S S 18L 1 synovial sarcoma translocation gene on 1.453659 0.02739503 chromosome 18-like 1

RALYL RALY RNA binding protein-like 1.453082 0.02632547 SYCP1 synaptonemal complex protein 1 1.453082 0.02072635 CCDC69 coiled-coil domain containing 69 1.452643 0.02816828 ALPI alkaline phosphatase, intestinal 1.452631 0.02222572

OPvMl #N/A 1.452285 0.04195743 RFX1 regulatory factor X, 1 (influences HLA class II 1.452074 0.00875266 expression)

TNRC6A trinucleotide repeat containing 6A 1.452047 0.02369483

HIP1R huntingtin interacting protein 1 related 1.451914 0.03461542

C2orf44 chromosome 2 open reading frame 44 1.451775 0.04320389

COROIB #N/A 1.451356 0.02900698

COLEC11 #N/A 1.45121 0.04062806

CCDC158 coiled-coil domain containing 158 1.451079 0.02115158

RNF121 #N/A 1.450747 0.0323907

SCNM1 sodium channel modifier 1 1.450562 0.01556104

ZNF277 zinc finger protein 277 1.45051 0.00702043

MOSPD2 motile sperm domain containing 2 1.450267 0.02091263

ATP5L2 ATP synthase, H+ transporting, mitochondrial F0 1.450265 0.02530962 complex, subunit G2

C9orfl26 Chromosome 9 open reading frame 126 1.450191 0.04664219 CYR61 cysteine-rich, angiogenic inducer, 61 1.449852 0.0419131 DNAJC6 DnaJ (Hsp40) homolog, subfamily C, member 6 1.449841 0.02353657 C20orf7 chromosome 20 open reading frame 7 1.449502 0.02641157 SRRM1 serine/arginine repetitive matrix 1 1.449417 0.01719139 TCF3 transcription factor 3 (E2A immunoglobulin 1.448743 0.04618902 enhancer binding factors E12/E47)

LYPD4 LY6/PLAUR domain containing 4 1.448653 0.04099551 STK19 serine/threonine kinase 19 1.448622 0.02320913 ITGAX integrin, alpha X (complement component 3 1.448498 0.01016974 receptor 4 subunit)

HISPPD1 Histidine acid phosphatase domain containing 1 1.448177 0.02992748 IL2RG interleukin 2 receptor, gamma (severe combined 1.448103 0.02567381 immunodeficiency)

BBC3 BCL2 binding component 3 1.448083 0.04661435

LAMA1 Laminin, alpha 1 1.447955 0.00196975

TIMM44 translocase of inner mitochondrial membrane 44 1.447869 0.00689012 homolog (yeast)

KCNV2 potassium channel, subfamily V, member 2 1.447764 0.03217123 C19orf21 #N/A 1.447582 0.0257192 PPM IE protein phosphatase, Mg2+/Mn2+ dependent, IE 1.447264 0.00842577 GLRA1 #N/A 1.447023 0.04108724 ZNF790 zinc finger protein 790 1.446844 0.02823732 VAV1 vav 1 guanine nucleotide exchange factor 1.446454 0.01174777 ARIH1 ariadne homolog, ubiquitin-conjugating enzyme 1.446394 0.0394967

E2 binding protein, 1 (Drosophila)

SYPL1 synaptophysin-like 1 1.446376 0.01547058 MYBPC1 myosin binding protein C, slow type 1.44631 0.00222751 ANKRDl #N/A 1.446181 0.03770147

DB1/ 694₃7516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

6

SGSM3 small G protein signaling modulator 3 1.446031 0.04389755

C2orf3 chromosome 2 open reading frame 3 1.446 0.03568188

LIPH lipase, member H 1.445989 0.02448008

BAT2L #N/A 1.445576 0.04009661 UFY3 RUN and FYVE domain containing 3 1.445443 0.02270059

CCDC78 coiled-coil domain containing 78 1.445173 0.037721 15

HAL histidine ammonia-lyase 1.44516 0.03368006

CALN1 calneuron 1 1.444981 0.01319932

RB1CC1 RBI -inducible coiled-coil 1 1.444531 0.03852258

LDOC1L #N/A 1.444205 0.00918373

SYCP2L synaptonemal complex protein 2-like 1.444066 0.04655165

NLE1 #N/A 1.443846 0.00933605

ME1 malic enzyme 1 , NADP(+)-dependent, cytosolic 1.443794 0.04664603

CLIP4 CAP-GLY domain containing linker protein 1.443751 0.03989778 family, member 4

MST1R macrophage stimulating 1 receptor (c-met-related 1.443731 0.0363428 tyrosine kinase)

LIN9 lin-9 homolog (C. elegans) 1.443332 0.04299003 ABCC6 ATP-binding cassette, sub-family C (CFTR/MRP), 1.443182 0.02894376 member 6

C9orf 5 chromosome 9 open reading frame 95 1.443106 0.02650312

ATP6V1C ATPase, H+ transporting, lysosomal 42kDa, VI 1.443098 0.0320308

1 subunit C 1

TYK2 tyrosine kinase 2 1.442974 0.02785366 CNA5 potassium voltage-gated channel, shaker-related 1.442627 0.02893599 subfamily, member 5

FAM90A1 family with sequence similarity 90, member Al 1.44242 0.03069489

NOL10 nucleolar protein 10 1.44239 0.03303329

PMM2 phosphomannomutase 2 1.44225 0.002484

ADD1 adducin 1 (alpha) 1.440954 0.01023506

ACTR3B ARP3 actin-related protein 3 homolog B (yeast) 1.440505 0.04469901

SLC9A11 solute carrier family 9, member 11 1.440442 0.00161565

FUT10 Fucosyltransferase 10 (alpha (1,3) 1.440327 0.01438755 fucosyltransferase)

PTPRB protein tyrosine phosphatase, receptor type, B 1.440166 0.01445378

STK32B serine/threonine kinase 32B 1.439922 0.03858143

WDR27 WD repeat domain 27 1.439524 0.0262986

CNTNAP contactin associated protein 1 1.439432 0.03843804

1

ZBTB46 zinc finger and BTB domain containing 46 1.439424 0.038251 11 GIMAP5 GTPase, IMAP family member 5 1.438945 0.00841291 CYP3A4 cytochrome P450, family 3, subfamily A, 1.438913 0.01268167 polypeptide 4

USH1C Usher syndrome 1C (autosomal recessive, severe) 1.438859 0.02836779

UBASH3 ubiquitin associated and SH3 domain containing A 1.438688 0.03138061

A

RECQL4 RecQ protein-like 4 1.438547 0.0083977

CTNS cystinosis, nephropathic 1.438438 0.04635666

ADAMTS ADAM metallopeptidase with thrombospondin 1.438398 0.03994317 1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

20 type 1 motif, 20

UHRF 1 BP UHRF 1 binding protein 1 -like 1.438167 0.03812257

1L

ANKLE 1 #N/A 1.437936 0.04289526

TTC31 tetratricopeptide repeat domain 31 1.437808 0.02034163

ZNF555 #N/A 1.437694 0.0221519

PPT1 palmitoyl-protein thioesterase 1 1.437618 0.03650416

MYOIA myosin IA 1.437578 0.00922217

RGL1 #N/A 1.437538 0.03518842

MAP7D2 MAP7 domain containing 2 1.437516 0.04660429

ERO 1 LB ERO 1 -like beta (S . cerevisiae) 1.437396 0.04436835

CHML choroideremia-like (Rab escort protein 2) 1.437277 0.01684899

ZNF33 zinc finger protein 334 1.437135 0.03342691

CCDC80 coiled-coil domain containing 80 1.436846 0.04107733

DDIT4 DNA-damage-inducible transcript 4 1.436743 0.028691

LRP2 low density lipoprotein receptor-related protein 2 1.436559 0.04792878

HAX 1 HCLS 1 associated protein X- 1 1.436401 0.0031628

MPZL1 myelin protein zero-like 1 1.436367 0.02987305

REV1 REV1 homolog (S. cerevisiae) 1.43625 0.01090101

GGPS 1 geranylgeranyl diphosphate synthase 1 1.436175 0.03585913

ZNF510 zinc finger protein 510 1.435712 0.01885009

RGS 13 regulator of G-protein signaling 13 1.435473 0.00771751

RNF 185 ring finger protein 185 1.435054 0.04045667

BBS5 Bardet-Biedl syndrome 5 1.43494 0.0399247

NKIRAS 1 NFKB inhibitor interacting Ras-like 1 1.434868 0.041 11426

CHRNB3 #N/A 1.434463 0.03870342

TMOD2 tropomodulin 2 (neuronal) 1.434447 0.01317972

CD163L1 CD163 molecule-like 1 1.434359 0.00184705

SHC4 SHC (Src homology 2 domain containing) family, 1.434304 0.01868442 member 4

PHLDA3 pleckstrin homology-like domain, family A, 1.433973 0.03894901 member 3

PPP 1 R3 A protein phosphatase 1 , regulatory (inhibitor) 1.43373 0.03032323 subunit 3 A

CCDC79 coiled-coil domain containing 79 1.433536 0.02680449

UGP2 UDP-glucose pyrophosphorylase 2 1.433359 0.01879469

PTPRD protein tyrosine phosphatase, receptor type, D 1.43321 0.02320547

STAG3 stromal antigen 3 1.433114 0.02444196

PRRC1 proline-rich coiled-coil 1 1.433027 0.04478808

ARMC8 armadillo repeat containing 8 1.432874 0.04852029

PARP9 poly (ADP-ribose) polymerase family, member 9 1.432814 0.04964132

DTWD2 DTW domain containing 2 1.432515 0.0493533

UNQ6494 QCWQ6494 1.432382 0.02496361

ZMYM4 zinc finger, MYM-type 4 1.432183 0.03154925

C8orf54 chromosome 8 open reading frame 54 1.431962 0.03299928

MTF2 metal response element binding transcription 1.431461 0.04435086 factor 2

UBA5 ubiquitin-like modifier activating enzyme 5 1.431379 0.04616022

C5orf46 chromosome 5 open reading frame 46 1.431223 0.01793586

RNF 19 A ring finger protein 19 A 1.431067 0.01581715 1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

INTS4L1 integrator complex subunit 4-like 1 1.430936 0.02783269 POLR1B polymerase (RNA) I polypeptide B, 128kDa 1.430873 0.01550162 MLH1 mutL homolog 1, colon cancer, nonpolyposis type 1.430761 0.00794245

2 (E. coli)

GFM2 G elongation factor, mitochondrial 2 1.430555 0.01383552

ANKRD1 ankyrin repeat domain 17 1.43046 0.04827993

7

FAF1 Fas (TNFRSF6) associated factor 1 1.430121 0.03904638

COX10 #N/A 1.430118 0.03538123

C2orf56 chromosome 2 open reading frame 56 1.430048 0.03348655

ZNF19 #N/A 1.429972 0.01649419

MFHAS1 #N/A 1.429933 0.04621658

ZFAND2 zinc finger, AN1 -type domain 2B 1.429775 0.01879494

B

ADCY2 Adenylate cyclase 2 (brain) 1.429756 0.03216495

EPHA7 EPH receptor A7 1.429676 0.03132041

PAPOLG poly(A) polymerase gamma 1.429616 0.04792028

BCL2L13 BCL2-like 13 (apoptosis facilitator) 1.429059 0.02860466

ARFGAP ADP-ribosylation factor GTPase activating protein 1.428814 0.04525843

1 1

LCORL ligand dependent nuclear receptor corepressor-like 1.428736 0.04488822

NXF4 nuclear RNA export factor 4 pseudogene 1.428667 0.01643294

IGHG2 #N/A 1.428576 0.04018687

OVOL2 ovo-like 2 (Drosophila) 1.428425 0.03844006

PTPRZ1 protein tyrosine phosphatase, receptor-type, Z 1.428389 0.04422762 polypeptide 1

SNX2 sorting nexin 2 1.428357 0.04171181

NCOR1 nuclear receptor co-repressor 1 1.427976 0.04923058

C14orf45 Chromosome 14 open reading frame 45 1.427883 0.01624658

SYTL4 synaptotagmin-like 4 1.427768 0.0322787

LDHC #N/A 1.427546 0.03619496

LENG9 leukocyte receptor cluster (LRC) member 9 1.427372 0.02993145

DCHS1 dachsous 1 (Drosophila) 1.427318 0.0121132

SLC17A5 solute carrier family 17 (anion/sugar transporter), 1.42719 0.02150945 member 5

TRMU tRNA 5-methylaminomethyl-2-thiouridylate 1.427064 0.01700529 methyltransferase

LRRC52 #N/A 1.426523 0.04028452

WDR41 WD repeat domain 41 1.426471 0.00680616

C5orf48 chromosome 5 open reading frame 48 1.426459 0.04189294

MGC1638 Hypothetical protein MGC 16385 1.426454 0.02062426

5

C5orf37 Chromosome 5 open reading frame 37 1.425784 0.00637019

MED 19 mediator complex subunit 19 1.425713 0.03386226

DERL2 Deri-like domain family, member 2 1.425344 0.02794415

KLHL30 #N/A 1.4249 0.04129442

C22orf43 #N/A 1.424794 0.04583136

ACTL6A actin-like 6A 1.42451 0.04623304

ALOX5A #N/A 1.424267 0.00272828

DB1/ 69437516. I Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

LTBP1 latent transforming growth factor beta binding 1.424099 0.04996473 protein 1

SPG11 Spastic paraplegia 11 (autosomal recessive) 1.423899 0.03021136

NXF3 nuclear RNA export factor 3 1.423693 0.03537481

LAMA4 laminin, alpha 4 1.423591 0.04403999

SLC26A1 Solute carrier family 26, member 11 1.423394 0.0442195

1

MOBKL1 MOBl, Mps One Binder kinase activator-like 1A 1.423253 0.02598551

A (yeast)

IL8 #N/A 1.423252 0.03879855

EIF2AK1 eukaryotic translation initiation factor 2-alpha 1.42324 0.02190845 kinase 1

RBPMS RNA binding protein with multiple splicing 1.422673 0.04119182 BRE brain and reproductive organ-expressed 1.422448 0.02514955

(TNFRSF1 A modulator)

NCK1 NCK adaptor protein 1 1.422439 0.03578054 DRAP1 #N/A 1.422065 0.03621038 RUNDC3 RUN domain containing 3B 1.421857 0.04330288 B

SYNJ2BP #N/A 1.421739 0.02283196 PDE7B phosphodiesterase 7B 1.421678 0.03688497 PDK1 pyruvate dehydrogenase kinase, isozyme 1 1.421279 0.03042126 SLC28A3 solute carrier family 28 (sodium-coupled 1.420863 0.04586862 nucleoside transporter), member 3

DPM2 dolichyl-phosphate mannosyltransferase 1.42053 0.00599389 polypeptide 2, regulatory subunit

SCYL1 SCYl-like 1 (S. cerevisiae) 1.42052 0.04474295

C6orfl65 chromosome 6 open reading frame 165 1.420502 0.00218418

KIR3DL1 killer cell immunoglobulin-like receptor, three 1.420189 0.01360711 domains, long cytoplasmic tail, 1

SLC25A3 solute carrier family 25 (mitochondrial carrier; 1.420003 0.02483151 phosphate carrier), member 3

ZNF212 #N/A 1.419877 0.02511564

ACSBG2 acyl-CoA synthetase bubblegum family member 2 1.419763 0.04014889

LEKR1 #N/A 1.419752 0.04682436

MTUS1 microtubule associated tumor suppressor 1 1.418787 0.03798287

MY01B myosin IB 1.418658 0.00197662

MIOX #N/A 1.418575 0.04954692

ALS2CR4 amyotrophic lateral sclerosis 2 (juvenile) 1.418546 0.0310462 chromosome region, candidate 4

DI03 deiodinase, iodothyronine, type III 1.418513 0.00819247

CALCB #N/A 1.418355 0.00838483

ME2 malic enzyme 2, NAD(+)-dependent, 1.418274 0.01841145 mitochondrial

CAGE1 cancer antigen 1 1.418164 0.03913329 GPBP1L1 GC-rich promoter binding protein 1 -like 1 1.418033 0.04799429 PLA2R1 phospholipase A2 receptor 1, 180kDa 1.417542 0.00923605 GPSM1 G-protein signaling modulator 1 (AGS 3 -like, C. 1.417471 0.04785931 elegans)

CHP2 calcineurin B homologous protein 2 1.41739 0.04969681 1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

NUMB numb homolog (Drosophila) 1.417215 0.02478936

AOC2 amine oxidase, copper containing 2 (retina- 1.417046 0.01426703 specific)

TRERF 1 transcriptional regulating factor 1 1.416101 0.03254844

RAPGEFl Rap guanine nucleotide exchange factor (GEF) 1 1.415895 0.04265785

CTH cystathionase (cystathionine gamma-lyase) 1.415796 0.0428465

PCDH24 #N/A 1.415716 0.0291154

PISD #N/A 1.415277 0.03084606

TTC25 tetratricopeptide repeat domain 25 1.415135 0.00096534

DIP2C DIP2 disco-interacting protein 2 homolog C 1.415117 0.03521672

(Drosophila)

KCNK17 potassium channel, subfamily K, member 17 1.415067 0.04872156

CPS1 carbamoyl-phosphate synthase 1 , mitochondrial 1.415049 0.02220611

LSM12 #N/A 1.414925 0.04599678

RDH10 #N/A 1.4149 0.0303362

PIP5K1C phosphatidylinositol-4-phosphate 5-kinase, type I, 1.414862 0.03680471 gamma

AGRP #N/A 1.414749 0.03624587

KISS1R KISS1 receptor 1.414596 0.04660972

CEP170L #N/A 1.414297 0.00533912

TFB2M transcription factor B2, mitochondrial 1.414276 0.00766602

ARAP3 ArfGAP with RhoGAP domain, ankyrin repeat 1.414139 0.04810273 and PH domain 3

ATP6V1G ATPase, H+ transporting, lysosomal 13kDa, VI 1.413912 0.01696754

2 subunit G2

OR51F1 #N/A 1.413838 0.02868178

ARFIP2 ADP-ribosylation factor interacting protein 2 1.413806 0.00699041

GTF3C3 general transcription factor IIIC, polypeptide 3, 1.413757 0.03007023

102kDa

PRDM15 PR domain containing 15 1.413293 0.03857759

MPDZ multiple PDZ domain protein 1.413148 0.00731358

FXR2 fragile X mental retardation, autosomal homolog 2 1.413137 0.04479532

CLEC1A #N/A 1.412984 0.0237952

HADH #N/A 1.412827 0.01477945

FRAP 1 FK506 binding protein 12-rapamycin associated 1.412768 0.03216416 protein 1

TAPBP TAP binding protein (tapasin) 1.412705 0.01852405

GPR126 G protein-coupled receptor 126 1.412461 0.03202184

VEPH1 ventricular zone expressed PH domain homolog 1 1.412406 0.04250664

(zebrafish)

DDB 1 damage-specific DNA binding protein 1 , 127kDa 1.41234 0.0326726

PODN podocan 1.412215 0.02049473

C14orfl77 chromosome 14 open reading frame 177 1.412036 0.01060699

NADK NAD kinase 1.411726 0.04453067

PRKACB protein kinase, cAMP-dependent, catalytic, beta 1.411632 0.04890563

MRGPRX #N/A 1.41 157 0.04440184 1

LASS1 LAG1 homolog, ceramide synthase 1 1.411301 0.03143383

CA11 carbonic anhydrase XI 1.411239 0.02467048

TAF7L TAF7-like RNA polymerase II, TATA box 1.411168 0.03198948 1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

binding protein (TBP)-associated factor, 50kDa

LOC1586 hypothetical LOCI 58696 1.411086 0.02489639 96

SPEF2 sperm flagellar 2 1.411013 0.01013766

SAMD4A sterile alpha motif domain containing 4A 1.410742 0.03063432

C8orf44 #N/A 1.410533 0.01332613

HIST1H3J histone cluster 1 , H3j 1.410359 0.00103398

PON2 paraoxonase 2 1.410181 0.02722414

ZNF71 #N/A 1.410135 0.04534524

BTNL8 butyrophilin-like 8 1.410086 0.02585348

PEX16 #N/A 1.409984 0.01029936

EYA1 eyes absent homolog 1 (Drosophila) 1.409781 0.01320983

FAM54B family with sequence similarity 54, member B 1.409645 0.00862757

BRD3 #N/A 1.409586 0.00784168

LOC7282 #N/A 1.409519 0.04143559

12

SPEG #N/A 1.409468 0.00375427

TBRG4 #N/A 1.40939 0.02950791

ROPN1B #N/A 1.408993 0.00790338

SNAP47 synaptosomal-associated protein, 47kDa 1.408485 0.04602921

AKAP9 A kinase (PRKA) anchor protein (yotiao) 9 1.408331 0.0397578

TIGD5 tigger transposable element derived 5 1.408267 0.020565

C14orf79 chromosome 14 open reading frame 79 1.408188 0.03685775

C8orf79 Chromosome 8 open reading frame 79 1.40808 0.01438085

ZBED4 zinc finger, BED-type containing 4 1.407985 0.01114324

PTPN12 protein tyrosine phosphatase, non-receptor type 12 1.407633 0.04343223

FAM91A1 family with sequence similarity 91, member Al 1.407477 0.01878871

G2E3 G2/M-phase specific E3 ubiquitin ligase 1.407412 0.0340295

GALNT8 UDP-N-acetyl-alpha-D-galactosamine:polypeptide 1.407377 0.00638373

N-acetylgalactosaminyltransferase 8 (GalNAc-T8)

ANGPT1 #N/A 1.407237 0.04946848

ADRBK2 adrenergic, beta, receptor kinase 2 1.407184 0.03936594

TTLL10 tubulin tyrosine ligase-like family, member 10 1.407102 0.03185513

LPHN2 latrophilin 2 1.406759 0.03075214

POLR2C polymerase (RNA) II (DNA directed) polypeptide 1.406734 0.01483067

C, 3 kDa

GON4L gon-4-like (C. elegans) 1.406578 0.02792844

TJP2 tight junction protein 2 (zona occludens 2) 1.406495 0.04195112

CLEC4C #N/A 1.406452 0.01047827

CD34 CD34 molecule 1.406256 0.02143454

EIF4G3 eukaryotic translation initiation factor 4 gamma, 3 1.406204 0.00853982

KCMF1 potassium channel modulatory factor 1 1.406049 0.03966502

NLGN4X neuroligin 4, X-linked 1.405981 0.04808391

SYT4 #N/A 1.405821 0.02588059

PGAP1 post-GPI attachment to proteins 1 1.40579 0.04981905

HCRTR2 hypocretin (orexin) receptor 2 1.405277 0.04487237

MBD3L1 #N/A 1.405222 0.00721026

ERCC4 excision repair cross-complementing rodent repair 1.405166 0.04499256 deficiency, complementation group 4

KRTAP13 #N/A 1.404759 0.0428822

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

-1

TRNAU1 tRNA selenocysteine 1 associated protein 1 1.404681 0.04311386

AP

IPO 1 1 importin 1 1 1.404451 0.04851699

C16orf52 Chromosome 16 open reading frame 52 1.404438 0.03309352

CPXM2 carboxypeptidase X (Ml 4 family), member 2 1.40407 0.02406586

ARPC2 actin related protein 2/3 complex, subunit 2, 1.403844 0.04550945

34kDa

FAM129C family with sequence similarity 129, member C 1.403626 0.0330672

RABGEF RAB guanine nucleotide exchange factor (GEF) 1 1.403497 0.03434929

1

TCEB3 transcription elongation factor B (SIII), 1.403204 0.03240308 polypeptide 3 (1 lOkDa, elongin A)

RYR2 ryanodine receptor 2 (cardiac) 1.403032 0.03605059

GHDC GH3 domain containing 1.402837 0.01882408

SERTAD4 SERTA domain containing 4 1.402681 0.00359257

KCNT2 Potassium channel, subfamily T, member 2 1.402521 0.04560752

CLSPN claspin homolog (Xenopus laevis) 1.402502 0.02545263

MOCS1 molybdenum cofactor synthesis 1 1.402262 0.00758675

DCT #N/A 1.402217 0.01437619

NLRP9 NLR family, pyrin domain containing 9 1.402215 0.04470192

CACNA2 calcium channel, voltage-dependent, alpha 2/delta 1.402206 0.03725548

D4 subunit 4

SLC25A3 solute carrier family 25 (mitochondrial carrier; 1.402178 0.03455203 1 adenine nucleotide translocator), member 31

ALDH4A aldehyde dehydrogenase 4 family, member Al 1.402143 0.0428196 1

ZNF12 zinc finger protein 12 1.402106 0.02420556

MYL4 myosin, light chain 4, alkali; atrial, embryonic 1.401793 0.02323071

CELP carboxyl ester lipase pseudogene 1.401509 0.04098698

OLFML2 olfactomedin-like 2B 1.40142 0.03843012

B

DPY19L2 dpy-19-like 2 (C. elegans) 1.401349 0.03991465 CCDC48 coiled-coil domain containing 48 1.401291 0.02399671 WDR60 WD repeat domain 60 1.401204 0.01727148 MDGA1 MAM domain containing 1.400745 0.03911931 glycosylphosphatidylinositol anchor 1

CCDC150 coiled-coil domain containing 150 1.400713 0.00923587 SLC38A9 solute carrier family 38, member 9 1.40062 0.03176665 FRMPD2 FERM and PDZ domain containing 2 1.40054 0.00373957 ABTB2 ankyrin repeat and BTB (POZ) domain containing 1.400178 0.0245051

2

UPB1 ureidopropionase, beta 1.399598 0.02286101 TSN translin 1.399509 0.03659249 WASF1 WAS protein family, member 1 1.399399 0.01274934 PIGO phosphatidylinositol glycan anchor biosynthesis, 1.398797 0.04188742 class O

C7orf29 #N/A 1.398712 0.03424425

RHPN1 rhophilin, Rho GTPase binding protein 1 1.39868 0.01520561

COR02A #N/A 1.398661 0.03986101

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

ACSM3 acyl-CoA synthetase medium-chain family 1.398465 0.01871956 member 3

D4S234E DNA segment on chromosome 4 (unique) 234 1.398344 0.04212178 expressed sequence

ATP11B ATPase, class VI, type 1 IB 1.398172 0.04591405

TCOF1 Treacher Collins-Franceschetti syndrome 1 1.398069 0.0391157

GALT galactose- 1 -phosphate uridylyltransferase 1.397966 0.00247261

HRG histidine-rich glycoprotein 1.397856 0.03777067

R1IAG #N/A 1.39752 0.03485837

LOC6469 twelve-thirteen translocation leukemia gene 1.397169 0.00873384

82

AUP1 ancient ubiquitous protein 1 1.396355 0.02026702

PHF3 PHD finger protein 3 1.39621 1 0.01054891

RGPD5 RANBP2-like and GRIP domain containing 5 1.396117 0.04893838

S100A14 #N/A 1.396006 0.0066653

HSD17B1 hydroxysteroid (17-beta) dehydrogenase 11 1.395945 0.03304075

1

CACNA1 calcium channel, voltage-dependent, T type, alpha 1.395622 0.03864677 H 1H subunit

TRIM68 #N/A 1.395566 0.04779924 SCN10A sodium channel, voltage-gated, type X, alpha 1.395546 0.03812938 subunit

SPAG17 sperm associated antigen 17 1.395519 0.0299796 KRT20 keratin 20 1.395271 0.03217697 DGAT2L6 diacylglycerol O-acyltransferase 2-like 6 1.395177 0.02714545 MS4A10 Membrane-spanning 4-domains, subfamily A, 1.394905 0.0318291 member 10

POSTN periostin, osteoblast specific factor 1.394528 0.00856569

CLEC4G #N/A 1.394409 0.01651661

LQK1 LQK1 hypothetical protein short isoform 1.39403 0.02557725

FM04 #N/A 1.393464 0.02372092

CABP2 #N/A 1.393445 0.04869489

CD83 CD83 molecule 1.393225 0.03750887

RAB39B #N/A 1.3926 0.00729975

C10orf58 #N/A 1.392475 0.0313261

UBC #N/A 1.39239 0.04488279

SLC3A1 solute carrier family 3 (cystine, dibasic and neutral 1.392282 0.03412927 amino acid transporters, activator of cystine,

dibasic and neutral amino acid transport), member

1

1

SEPP1 selenoprotein P, plasma, 1 1.392278 0.01276165

HRC histidine rich calcium binding protein 1.392189 0.02392761

NCSTN nicastrin 1.39212 0.03276348

PER3 period homolog 3 (Drosophila) 1.391761 0.04590857

ITGB8 integrin, beta 8 1.391437 0.01007626

G3BP2 GTPase activating protein (SH3 domain) binding 1.391061 0.03995435 protein 2

DMBT1 deleted in malignant brain tumors 1 1.391016 0.01095332

ERBB2IP erbb2 interacting protein 1.390929 0.00826632

NCRNAO non-protein coding RNA 174 1.390833 0.01828585 1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

0174

ABCA3 #N/A 1.390303 0.04042122

ARMC3 armadillo repeat containing 3 1.39017 0.02418178

GAA glucosidase, alpha; acid 1.390145 0.02416388

WDR16 WD repeat domain 16 1.389763 0.00382488

MAP3K7 mitogen-activated protein kinase kinase kinase 7 1.389714 0.01863856

WDR35 WD repeat domain 35 1.38932 0.03314722

TTF1 transcription termination factor, RNA polymerase 1.38918 0.01861324

I

EHMT2 euchromatic histone-lysine N-methyltransferase 2 1.389037 0.04529926

SP140L SP140 nuclear body protein-like 1.388923 0.0361833

CUL2 cullin 2 1.388834 0.03417199

PDYN prodynorphin 1.388793 0.01792923

GSK3B glycogen synthase kinase 3 beta 1.388704 0.01324586

DDX59 DEAD (Asp-Glu- Ala-Asp) box polypeptide 59 1.38866 0.01161362

FEZ2 fasciculation and elongation protein zeta 2 (zygin 1.388464 0.01625731

Π)

NUAK2 NUAK family, SNFl-like kinase, 2 1.388457 0.00947788

ITLN2 intelectin 2 1.388199 0.04185219

RNF149 ring finger protein 149 1.388136 0.03753609

ZFYVE20 zinc finger, FYVE domain containing 20 1.388131 0.03685951

PIWIL3 Piwi-like 3 (Drosophila) 1.388125 0.04611083

ZNF230 zinc finger protein 230 1.388118 0.01064806

RAB27B RAB27B, member RAS oncogene family 1.387967 0.0450371

RRP9 ribosomal RNA processing 9, small subunit (SSU) 1.38781 0.02464482 processome component, homolog (yeast)

C17orf53 chromosome 17 open reading frame 53 1.38774 0.0078672

2-Sep #N/A 1.387431 0.03338744 FUCA1 fucosidase, alpha-L- 1, tissue 1.38741 0.02925501 PDCD11 programmed cell death 11 1.387102 0.04328171 CATSPER Cation channel, sperm associated 2 pseudogene 1 1.386958 0.03847495 2P1

FLJ44881 FLJ44881 1.386885 0.04903313

SNAPC5 #N/A 1.386849 0.00725544

C20orf71 chromosome 20 open reading frame 71 1.386461 0.04746647 CNIP2 Kv channel interacting protein 2 1.386433 0.03326746

BMP2K BMP2 inducible kinase 1.386192 0.04872796

NR2E3 nuclear receptor subfamily 2, group E, member 3 1.386135 0.0494817

HEYL hairy/enhancer-of-split related with YRPW motif1.386075 0.03114455 like

ATP5D #N/A 1.386046 0.03800337

STAP2 #N/A 1.385918 0.04606399

ACAT2 acetyl-CoA acetyltransferase 2 1.385302 0.02677085

CCDC17 coiled-coil domain containing 17 1.385042 0.04001854

PIN1L peptidylprolyl cis/trans isomerase, NIMA- 1.384965 0.04185282 interacting 1 -like (pseudogene)

KIAA119 KIAA1191 1.38493 0.02319146 1

FLOT1 flotillin 1 1.384924 0.03926247 FAM83C family with sequence similarity 83, member C 1.384922 0.03647672

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P

Symbol Change value

RFXANK regulatory factor X-associated ankyrin-containing 1.384612 0.03248029 protein

JARID2 jumonji, AT rich interactive domain 2 1.384407 0.00690906

PIK3CG phosphoinositide-3 -kinase, catalytic, gamma 1.384287 0.01670825 polypeptide

EXOC3L2 exocyst complex component 3 -like 2 1.384174 0.03521837

PDXK pyridoxal (pyridoxine, vitamin B6) kinase 1.384091 0.03873832

MAGEB1 melanoma antigen family B, 1 1.383909 0.01558786

C5 complement component 5 1.38387 0.01555144

CASKIN2 C ASK interacting protein 2 1.383695 0.00978574

PYCRL pyrroline-5-carboxylate reductase-like 1.383376 0.02332003

CTDP1 CTD (carboxy-terminal domain, RNA polymerase 1.3832 0.02699086

II, polypeptide A) phosphatase, subunit 1

PRDX1 peroxiredoxin 1 1.38319 0.0314545

LASS2 LAG1 homolog, ceramide synthase 2 1.383183 0.01736726

FAM83A family with sequence similarity 83, member A 1.383114 0.02272562

ADAD2 adenosine deaminase domain containing 2 1.382822 0.0290104

ZYG11B zyg-11 homolog B (C. elegans) 1.382759 0.03637639

DGCR8 DiGeorge syndrome critical region gene 8 1.382451 0.01673764

SLC2A5 solute carrier family 2 (facilitated glucose/fructose 1.382214 0.02054184 transporter), member 5

CXorf22 chromosome X open reading frame 22 1.382178 0.02367145

GDAP2 ganglioside induced differentiation associated 1.381444 0.02555595 protein 2

PITX2 #N/A 1.38095 0.03603224

FARP2 FERM, RhoGEF and pleckstrin domain protein 2 1.380538 0.0362369

C4orf8 Chromosome 4 open reading frame 8 1.380393 0.04410986

DCP2 DCP2 decapping enzyme homolog (S. cerevisiae) 1.380372 0.02782318

RAB2A RAB2A, member RAS oncogene family 1.38031 0.02989203

SNX17 #N/A 1.38031 0.04778598

BLID #N/A 1.379936 0.04489691

FLJ26850 FLJ26850 protein 1.379795 0.0315004

SLC12A2 solute carrier family 12 1.379717 0.01203849

(sodium/potassium/chloride transporters), member

PHKA2 phosphorylase kinase, alpha 2 (liver) 1.379358 0.04156652

MAD2L1 #N/A 1.379319 0.02498422 BP

PUS10 pseudouridylate synthase 10 1.37928 0.03260097

GRHL1 grainyhead-like 1 (Drosophila) 1.379134 0.04726898

ARIH2 ariadne homolog 2 (Drosophila) 1.379092 0.04036547

SOX21 SRY (sex determining region Y)-box 21 1.379007 0.03381278

MAMDC2 MAM domain containing 2 1.378926 0.03908725

PLA2G2A phospholipase A2, group IIA (platelets, synovial 1.37892 0.02830803 fluid)

NGFRAP nerve growth factor receptor (TNFRSF16) 1.378697 0.03131 156

1 associated protein 1

SFTPA1 surfactant protein Al 1.378651 0.04576467

EML3 echinoderm microtubule associated protein like 3 1.378484 0.02696298

GSDMB gasdermin B 1.37845 0.044703071/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

Clorf83 chromosome 1 open reading frame 83 1.377876 0.03773114 R F14 ring finger protein 14 1.377805 0.04782365 SAT1 spermidine/spermine Nl-acetyltransferase 1 1.377678 0.0199371 TAF1L TAF1 RNA polymerase II, TATA box binding 1.377677 0.01341919 protein (TBP)-associated factor, 210kDa-like

AMT aminomethyltransferase 1.377596 0.04610355

TARSL2 threonyl-tRNA synthetase-like 2 1.37744 0.03384658

KCNMB1 #N/A 1.377197 0.01536732

EFNA5 ephrin-A5 1.376946 0.02612841

ULK1 unc-51-like kinase 1 (C. elegans) 1.376606 0.04913687

TESSP5 #N/A 1.376448 0.00800435

SOCS5 suppressor of cytokine signaling 5 1.37553 0.01917031

CLPX ClpX caseinolytic peptidase X homolog (E. coli) 1.375441 0.01468959

LNX2 Ligand of numb-protein X 2 1.375437 0.04247097

GLS glutaminase 1.375186 0.03479203

BMP4 bone morphogenetic protein 4 1.375126 0.01823714

EBF4 early B-cell factor 4 1.374912 0.03180139

SCMH1 sex comb on midleg homolog 1 (Drosophila) 1.374893 0.04735748

SERPINB serpin peptidase inhibitor, clade B (ovalbumin), 1.374614 0.04079695

13 member 13

CYBA cytochrome b-245, alpha polypeptide 1.374566 0.01905461

SECISBP SECIS binding protein 2-like 1.374566 0.04433205

2L

CLCNKA chloride channel Ka 1.374472 0.03583901

TM7SF4 transmembrane 7 superfamily member 4 1.37444 0.04083846

FLJ40852 #N/A 1.374363 0.04940007

C6orf54 #N/A 1.374323 0.02034623

HIF3A Hypoxia inducible factor 3, alpha subunit 1.3743 0.03370266

CGNL1 cingulin-like 1 1.374127 0.02383984

C14orf49 chromosome 14 open reading frame 49 1.374057 0.0211786

RHOBTB Rho-related BTB domain containing 3 1.373996 0.01988465

3

ELP3 elongation protein 3 homolog (S. cerevisiae) 1.373642 0.03955407 POLR2H polymerase (RNA) II (DNA directed) polypeptide 1.373227 0.02984487

H

KIAA131 KIAA1310 1.373158 0.04142218 0

SLC35A1 solute carrier family 35 (CMP-sialic acid 1.372979 0.0029421 transporter), member Al

NCRNAO non-protein coding RNA 175 1.372758 0.00985385

0175

Cl lorf35 #N/A 1.372583 0.04741799

FEZF2 FEZ family zinc finger 2 1.372156 0.01753083

NCKAP1 NC -associated protein 1 1.372116 0.02620886

9-Sep #N/A 1.371851 0.04857443 RTP4 #N/A 1.371731 0.04756939 CFTR cystic fibrosis transmembrane conductance 1.371604 0.03587373 regulator (ATP-binding cassette sub-family C,

member 7)

ST14 suppression of tumorigenicity 14 (colon 1.371459 0.03200038 1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

carcinoma)

AP3S1 adaptor-related protein complex 3, sigma 1 subunit 1.37125 0.0071826

FAM49B family with sequence similarity 49, member B 1.37124 0.04761414

SMARCA SWI/SNF related, matrix associated, actin 1.371225 0.01914396

2 dependent regulator of chromatin, subfamily a,

member 2

ACBD4 acyl-CoA binding domain containing 4 1.37122 0.03423982

EFCAB6 EF-hand calcium binding domain 6 1.370919 0.04000618

XAGE2 #N/A 1.370913 0.03807452

CTSS cathepsin S 1.370682 0.01961639

DOK5 docking protein 5 1.37065 0.00588661

ZNF3 zinc finger protein 3 1.370646 0.02001535

AN04 anoctamin 4 1.370627 0.04972677

ZBTB48 zinc finger and BTB domain containing 48 1.370607 0.00410921

TMEM 18 transmembrane protein 183 B 1.370591 0.04077533

3B

HDLBP high density lipoprotein binding protein 1.370587 0.02901277

SPAG7 sperm associated antigen 7 1.370365 0.04772279

QPCT glutaminyl -peptide cyclotransferase 1.370054 0.04693999

WDR33 WD repeat domain 33 1.369404 0.02111859

GPR132 #N/A 1.36932 0.04152648

KRT15 keratin 15 1.369198 0.02838278

EPS8L1 EPS8-like 1 1.368955 0.01719425

RGS5 #N/A 1.368892 0.01376485

MFAP3L microfibrillar-associated protein 3-like 1.368818 0.04260298

CLCA2 chloride channel accessory 2 1.368776 0.04106998

ATHL1 ATH1, acid trehalase-like 1 (yeast) 1.368744 0.00844971

USP6 ubiquitin specific peptidase 6 (Tre-2 oncogene) 1.36864 0.02369601

LZTFL1 leucine zipper transcription factor-like 1 1.368487 0.02321085

HSF4 #N/A 1.368486 0.04389483

BPY2 basic charge, Y-linked, 2 1.368245 0.04532575

CASS4 Cas scaffolding protein family member 4 1.368237 0.04868791

KLHL 10 kelch-like 10 (Drosophila) 1.368113 0.04173072

IL4R interleukin 4 receptor 1.367682 0.04745193

UQCRH ubiquinol-cytochrome c reductase hinge protein 1.367633 0.04991558

GALNT10 UDP-N-acetyl-alpha-D-galactosamine:polypeptide 1.367612 0.01578419

N-acetylgalactosaminyltransferase 10 (GalNAc-

T10)

SESTD1 SEC 14 and spectrin domains 1 1.366888 0.03597631

PPFIA2 protein tyrosine phosphatase, receptor type, f 1.366368 0.00766609 polypeptide (PTPRF), interacting protein (liprin),

alpha 2

EIF3M eukaryotic translation initiation factor 3, subunit M 1.366228 0.02809051

CDH18 cadherin 18, type 2 1.366148 0.00125786

SF3B1 splicing factor 3b, subunit 1, 155kDa 1.365473 0.04469656

ZMAT1 #N/A 1.36442 0.02781449

KCNJ14 potassium inwardly-rectifying channel, subfamily 1.364123 0.0248093

J, member 14

PALLD palladin, cytoskeletal associated protein 1.363762 0.04986509

ΓΝΡΡ4Β inositol polyphosphate-4-phosphatase, type II, 1.363494 0.00017936 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

105kDa

ABCB5 ATP-binding cassette, sub-family B (MDR/TAP), 1.363481 0.01402067 member 5

TFRC transferrin receptor (p90, CD71) 1.363435 0.02452106

Clorfl22 chromosome 1 open reading frame 122 1.363401 0.03699855

PTH #N/A 1.363071 0.02032375

ZNF211 #N/A 1.362871 0.03284971

AEBP2 AE binding protein 2 1.362569 0.03985048

KIAA180 mixed lineage kinase 4 1.362362 0.00777953

4

ACSL5 acyl-CoA synthetase long-chain family member 5 1.362342 0.03073901

TNIP1 TNFAIP3 interacting protein 1 1.362235 0.02962173

HIST1H4 #N/A 1.362152 0.00134079

D

F8 coagulation factor VIII, procoagulant component 1.36153 0.0330432

RFX4 regulatory factor X, 4 (influences HLA class II 1.361522 0.03667079 expression)

CLEC1B #N/A 1.361151 0.02599373

C4orf30 Chromosome 4 open reading frame 30 1 .35993 0.03562827

RHCE #N/A 1.359475 0.03662927

KIAA196 KIAA1967 1.359378 0.0188366

7

LYN v-yes-1 Yamaguchi sarcoma viral related 1.359373 0.01200334 oncogene homolog

RPS6KA6 ribosomal protein S6 kinase, 90kDa, polypeptide 6 1.359313 0.01574272

KIRREL2 Kin of IRRE like 2 (Drosophila) 1.359171 0.04649818

TR1M14 tripartite motif-containing 14 1.359063 0.04936092

GPBP1 GC-rich promoter binding protein 1 1.359053 0.03480641

CGREF1 #N/A 1.358723 0.01457688

ZNF79 zinc finger protein 79 1.358718 0.04549962

HHIPL2 HHIP-like 2 1.358436 0.03833599

GRIN2B #N/A 1.358397 0.0075932

CATSPER cation channel, sperm associated 1 1.358087 0.03085318

1

AHNAK2 AHNAK nucleoprotein 2 1.357789 0.01594685 CXCL13 chemokine (C-X-C motif) ligand 13 1.357676 0.00878467 GTF2IRD GTF2I repeat domain containing 2 pseudogene 1.35742 0.04895984 2P

PCMT1 protein-L-isoaspartate (D-aspartate) O- 1.357331 0.00986394 methyltransferase

INPP5D inositol polyphosphate-5 -phosphatase, 145kDa 1.357218 0.03501015 ITGA4 integrin, alpha 4 (antigen CD49D, alpha 4 subunit 1.357003 0.03979787 of VLA-4 receptor)

SPAST spastin 1.356288 0.03786354

PRLH prolactin releasing hormone 1.356089 0.02371997

UTP6 UTP6, small subunit (SSU) processome 1.356011 0.03536297 component, homolog (yeast)

PKD2 polycystic kidney disease 2 (autosomal dominant) 1.355906 0.03251514 SUGT1L1 SGT1, suppressor of G2 allele of SKP1 like 1 (S. 1.35567 0.00885436 cerevisiae)

1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells Gene Gene Description Fold Ttest P

Symbol Change value

MFI2 antigen p97 (melanoma associated) identified by 1.355647 0.00363659 monoclonal antibodies 133.2 and 96.5

TMEM14 transmembrane protein 146 1.355608 0.02720724 6

TTTY6 testis-specific transcript, Y-linked 6 (non-protein 1.355107 0.0474792 coding)

ΓΠΗ3 inter-alpha (globulin) inhibitor H3 1.354798 0.02342705 ILDR1 immunoglobulin-like domain containing receptor 1.354615 0.02734741

1

MY018A myosin XVIIIA 1.354563 0.0434213 RIC8B resistance to inhibitors of cholinesterase 8 1.35437 0.03801956 homolog B (C. elegans)

CTN A3 Catenin (cadherin-associated protein), alpha 3 1.354368 0.03510529 GREB1 GREB1 protein 1.354247 0.04230805 KDM3B lysine (K)-specific demethylase 3B 1.35412 0.04179252 VIT #N/A 1.35379 0.02402971

NECAB2 N-terminal EF-hand calcium binding protein 2 1.353677 0.04090459 B4GALN beta-l,4-N-acetyl-galactosaminyl transferase 1 1.353321 0.00575749 Tl

PSMB7 #N/A 1.353301 0.04033224

TOPORS Topoisomerase I binding, arginine/serine-rich 1.353172 0.00192257

MAPK8 mitogen-activated protein kinase 8 1.352867 0.03733872

A2M alpha-2-macroglobulin 1.352659 0.01926322

PSMA7 proteasome (prosome, macropain) subunit, alpha 1.35225 0.03229301 type, 7

7-Mar #N/A 1.352115 0.00153926 RABGGT Rab geranylgeranyltransferase, alpha subunit 1.351954 0.0429941 A

S100A3 #N/A 1.351681 0.01844129

PGDS #N/A 1.351548 0.02579275

POLR3GL polymerase (RNA) III (DNA directed) polypeptide 1.351326 0.04224969

G (32kD)-like

PSTK phosphoseryl-tRNA kinase 1.35128 0.04649495

CEP350 centrosomal protein 350kDa 1.351128 0.03670049

KDM4C lysine (K)-specific demethylase 4C 1.351053 0.0176246

ACY1 aminoacylase 1 1.35078 0.00373775

RNF32 ring finger protein 32 1.350722 0.04810592

BMX BMX non-receptor tyrosine kinase 1.350412 0.03189594

ZNF804A zinc finger protein 804A 1.350319 0.015929

RPH3A rabphilin 3 A homolog (mouse) 1.349799 0.01617809

TARS threonyl-tRNA synthetase 1.349756 0.04996272

GPR133 G protein-coupled receptor 133 1.349679 0.02919616

Clorfl04 chromosome 1 open reading frame 104 1.349616 0.01600065

CATSPER cation channel, sperm associated 2 1.349606 0.03144666

2

FNBP4 formin binding protein 4 1.349354 0.00845931 MCM6 minichromosome maintenance complex 1.349263 0.03160563 component 6

SLC27A1 Solute carrier family 27 (fatty acid transporter), 1.349238 0.01250896 member 1

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Unregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

PHC1 polyhomeotic homolog 1 (Drosophila) 1.34907 0.04242083

PIN 1 PTEN induced putative kinase 1 1.348951 0.03249442

TP 1 thiamin pyrophosphokinase 1 1.348935 0.00061583

KRTAP1- #N/A 1.348868 0.02700125

5

KIR2DL1 killer cell immunoglobulin-like receptor, two 1.348833 0.04699831 domains, long cytoplasmic tail, 1

DSP desmoplakin 1.348754 0.04651279

MREl 1 A MREl 1 meiotic recombination 11 homolog A (S. 1.348564 0.00038333 cerevisiae)

SPAG9 sperm associated antigen 9 1.348534 0.03303382

CCDC11 coiled-coil domain containing 11 1.34835 0.04368236

ATP7B ATPase, Cu++ transporting, beta polypeptide 1.348154 0.03209184

WDR92 #N/A 1.347904 0.0438393

ITGB1BP integrin beta 1 binding protein 3 1.347859 0.00957784

3

BLMH bleomycin hydrolase 1.347696 0.03973197

PKD1L1 polycystic kidney disease 1 like 1 1.34761 0.01490888

PECR peroxisomal trans-2-enoyl-CoA reductase 1.347163 0.02598704

DNAH5 dynein, axonemal, heavy chain 5 1.346943 0.0280359

ZNF566 zinc finger protein 566 1.346867 0.00318496

CXorf26 chromosome X open reading frame 26 1.346699 0.01655183

ATXN7L2 ataxin 7-like 2 1.346592 0.02446553

HM13 #N/A 1.346496 0.03424705

PREPL prolyl endopeptidase-like 1.346456 0.03536804

MAST1 microtubule associated serine/threonine kinase 1 1.345867 0.01970894

PLRG1 pleiotropic regulator 1 (PRL1 homolog, 1.345685 0.00188631

Arabidopsis)

ETV7 ets variant 7 1.345592 0.00259091

MAGEF1 melanoma antigen family F, 1 1.345586 0.0427293

NELL1 NEL-like 1 (chicken) 1.345471 0.035416

KRT7 keratin 7 1.345142 0.04343201

METTL11 #N/A 1.345064 0.02375531

A

TRIM26 tripartite motif-containing 26 1.344982 0.04300975 KCNQ1 potassium voltage-gated channel, KQT-like 1.344976 0.04493967 subfamily, member 1

MTMR12 myotubularin related protein 12 1.34462 0.0317016 AMPH amphiphysin 1.344519 0.00793595 KCNK16 potassium channel, subfamily K, member 16 1.344179 0.01298541 CDKL2 cyclin-dependent kinase-like 2 (CDC2-related 1.343983 0.02627129 kinase)

ACBD3 acyl-CoA binding domain containing 3 1.343979 0.0088417 FH fumarate hydratase 1.343761 0.01764835

LAPTM5 lysosomal protein transmembrane 5 1.343236 0.03239693 EIF3I eukaryotic translation initiation factor 3, subunit I 1.342791 0.03408126 ADAMTS ADAM metallopeptidase with thrombospondin 1.341872 0.01615138 6 type 1 motif, 6

PDCD6IP programmed cell death 6 interacting protein 1.341445 0.02712429 SCGN secretagogin, EF-hand calcium binding protein 1.341209 0.03145203 1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

SHISA5 shisa homolog 5 (Xenopus laevis) 1.341148 0.04008168 COL4A1 collagen, type IV, alpha 1 1.340948 0.04402007 TMEM17 #N/A 1.340759 0.04828331 7

CTR9 Ctr9, Pafl/RNA polymerase II complex 1.340525 0.01367351 component, homolog (S. cerevisiae)

WFDC6 #N/A 1.340339 0.03996958 ME3 malic enzyme 3, NADP(+)-dependent, 1.34006 0.04596134 mitochondrial

FA 165B #N/A 1.339989 0.03564499

MOSPD3 motile sperm domain containing 3 1.339688 0.02672093

MED24 mediator complex subunit 24 1.338971 0.02234539

BCL3 B-cell CLL/lymphoma 3 1.338873 0.03515185

ZNF514 zinc finger protein 514 1.338774 0.03091846

Cl lorf49 #N/A 1.338751 0.00600807

REX04 REX4, RNA exonuclease 4 homolog (S. 1.338363 0.02795145 cerevisiae)

HNMT histamine N-methyltransferase 1.338353 0.01243209

ATPBD3 ATP binding domain 3 1.338268 0.03756416

XRCC1 X-ray repair complementing defective repair in 1.338228 0.02107989

Chinese hamster cells 1

ZKSCAN zinc finger with KRAB and SCAN domains 4 1.338143 0.01984388 4

GALC #N/A 1.337734 0.04874618

NBN nibrin 1.337492 0.01768605

C3orf31 chromosome 3 open reading frame 31 1.337435 0.03784451

WDR37 WD repeat domain 37 1.337261 0.04217673

DNASE1 deoxyribonuclease I-like 1 1.337125 0.0421296

LI

REV3L REV3-like, catalytic subunit of DNA polymerase 1.337028 0.03337764 zeta (yeast)

PRDM1 PR domain containing 1, with ZNF domain 1.336557 0.02794345 ASAP2 ArfGAP with SH3 domain, ankyrin repeat and PH 1.33651 0.04235299 domain 2

RNASE9 #N/A 1.336502 0.0239313

RAPGEF6 Rap guanine nucleotide exchange factor (GEF) 6 1.336214 0.03767711

MLLT3 myeloid/lymphoid or mixed-lineage leukemia 1.336207 0.0340955

(trithorax homolog, Drosophila); translocated to, 3

C20orf26 chromosome 20 open reading frame 26 1.33611 0.03564871

MUC20 mucin 20, cell surface associated 1.335759 0.03871754

ZNF271 zinc finger protein 271 1.335297 0.03003494

PTPRH protein tyrosine phosphatase, receptor type, H 1.335102 0.01121867

CUX1 cut-like homeobox 1 1.334955 0.00914826

KCNA2 #N/A 1.334755 0.0481631

MY015B Myosin XVB pseudogene 1.334657 0.03628165

SLC7A60 solute carrier family 7, member 6 opposite strand 1.334654 0.04940768

S

CFC1 cripto, FRL-1, cryptic family 1 1.33456 0.04856555 MLF1 myeloid leukemia factor 1 1.334552 0.00268692 TMEM14 transmembrane protein 143 1.334351 0.04652845

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P

Symbol Change value

3

PLEKHN pleckstrin homology domain containing, family N 1.333813 0.01866753

1 member 1

MRPL2 Mitochondrial ribosomal protein L2 1.332717 0.03136737

CCDC28 coiled-coil domain containing 28A 1.332415 0.00567554

A

Ά

EPS 15 epidermal growth factor receptor pathway 1.332325 0.00937505 substrate 15

ATRNL1 attractin-like 1 1.33231 0.0185885

HERC4 hect domain and RLD 4 1.331943 0.04639538

COL4A6 collagen, type IV, alpha 6 1.331762 0.01428058 DR kinase insert domain receptor (a type III receptor 1.331501 0.01894919 tyrosine kinase)

ASH1L ashl (absent, small, or homeotic)-like (Drosophila) 1.331452 0.03902654

LRP1 low density lipoprotein receptor-related protein 1 1.331309 0.01612126

HIVEP1 human immunodeficiency virus type I enhancer 1.331277 0.0248194 binding protein 1

JMJD5 jumonji domain containing 5 1.33103 0.04885443

OR5M8 #N/A 1.331012 0.01957739

BEND4 #N/A 1.330633 0.0084728

CRLF3 cytokine receptor-like factor 3 1.330569 0.00382624

CD1E #N/A 1.330247 0.03326038

CABC1 Chaperone, ABC1 activity of bcl complex 1.330152 0.02028036 homolog (S. pombe)

SFRS12IP SFRS12-interacting protein 1 1.330128 0.02220107

1

1

GPR110 G protein-coupled receptor 1 10 1.33003 0.03973178

ING4 inhibitor of growth family, member 4 1.3297 0.03081502

EPC2 enhancer of polycomb homolog 2 (Drosophila) 1.329573 0.00820874

FUCA2 fucosidase, alpha-L- 2, plasma 1.329563 0.00731294

STARD8 StAR-related lipid transfer (START) domain 1.32952 0.04361252 containing 8

NUFIP1 nuclear fragile X mental retardation protein 1.329454 0.04150613 interacting protein 1

TNR tenascin R (restrictin, janusin) 1.329092 0.04787231

ZNF33A zinc finger protein 33 A 1.328976 0.03675665

TCN1 transcobalamin I (vitamin B12 binding protein, R 1.328809 0.04566794 binder family)

RALY #N/A 1.32864 0.03824028

USP38 ubiquitin specific peptidase 38 1.328488 0.03761775

ACAD8 acyl-CoA dehydrogenase family, member 8 1.328208 0.00875427

OPLAH 5-oxoprolinase (ATP-hydrolysing) 1.328172 0.04351552

ISYNA1 #N/A 1.328122 0.02916504

RSI retinoschisin 1 1.328064 0.01333097

CLOCK clock homolog (mouse) 1.327919 0.02539796

ATF2 activating transcription factor 2 1.327908 0.00755993

SLC22A4 solute carrier family 22 (organic 1.327739 0.04834645 cation/ergothioneine transporter), member 4

BMP1 bone morphogenetic protein 1 1.32758 0.03343608

E2F1 #N/A 1.326853 0.01045809

DB1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

PGBD5 piggyBac transposable element derived 5 1.326672 0.03641358

KLK6 kallikrein-related peptidase 6 1.326072 0.00249616

LGTN ligatin 1.325635 0.01405736

ZNF174 zinc finger protein 174 1.325582 0.04896235

DAB2IP DAB2 interacting protein 1.325257 0.04430944

SYN1 synapsi l 1.324875 0.02786199

ERCC5 excision repair cross-complementing rodent repair 1.324623 0.03590136 deficiency, complementation group 5

S AMD 11 sterile alpha motif domain containing 11 1.324154 0.01895183

ZNF589 #N/A 1.324138 0.00889113

THBS2 thrombospondin 2 1.3241 1 0.01874047

C2orf30 Chromosome 2 open reading frame 30 1.323884 0.04549174

HUS1 HUS1 checkpoint homolog (S. pombe) 1.323836 0.02917873

FMNL2 formin-like 2 1.323786 0.03096367

NCRNAO non-protein coding R A 95 1.323578 0.02733894

0095

PIH1D2 PIH1 domain containing 2 1.32339 0.01962435

HOMER2 homer homolog 2 (Drosophila) 1.32314 0.04783618

CLI T1 clathrin interactor 1 1.322768 0.00691085

NTSR1 neurotensin receptor 1 (high affinity) 1.322725 0.0411674

FYN FYN oncogene related to SRC, FGR, YES 1.322618 0.04081056

RG9MTD RNA (guanine-9-) methyltransferase domain 1.322385 0.04548519 1 containing 1

EMR3 egf-like module containing, mucin-like, hormone 1.322343 0.03444567 receptor-like 3

C19orf57 chromosome 19 open reading frame 57 1.322321 0.02905814

C8orf71 chromosome 8 open reading frame 71 1.322233 0.01829096

SCP2 sterol carrier protein 2 1.322128 0.04065107

EPB41L3 Erythrocyte membrane protein band 4.1 -like 3 1.321635 0.03609417

ZFPL1 #N/A 1.321634 0.00795096

MRPL3 mitochondrial ribosomal protein L3 1.321518 0.01629641

VIPR1 vasoactive intestinal peptide receptor 1 1.321242 0.0371231

CDH7 cadherin 7, type 2 1.320862 0.04295083

RPUSD2 #N/A 1.320642 0.02988753

CENPL centromere protein L 1.320641 0.01894421

SEC24C SEC24 family, member C (S. cerevisiae) 1.320333 0.0213207

CAP1 CAP, adenylate cyclase-associated protein 1 1.320275 0.04107121

(yeast)

DNAJC5 #N/A 1.320198 0.04648958 G

PDE7A phosphodiesterase 7A 1.320185 0.04566021

RHOBTB Rho-related BTB domain containing 2 1.31986 0.02694967

2

DPH3 DPH3, KTI11 homolog (S. cerevisiae) 1.319688 0.04772026 UBXN4 UBX domain protein 4 1.319595 0.04250153 DDX58 DEAD (Asp-Glu-Ala-Asp) box polypeptide 58 1.31932 0.03201112 RNASEL ribonuclease L (2',5'-oligoisoadenylate synthetase- 1.3192 0.02589713 dependent)

ORC3L origin recognition complex, subunit 3-like (yeast) 1.318941 0.0211371 SLFN11 #N/A 1.318215 0.02826722 1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

SH3RF1 SH3 domain containing ring finger 1 1.317529 0.00683851

WASF2 WAS protein family, member 2 1.316983 0.02117985

POGZ pogo transposable element with ZNF domain 1.316888 0.03835929

AKAP13 A kinase (PRKA) anchor protein 13 1.316226 0.0189134

PPP1R1B Protein phosphatase 1, regulatory (inhibitor) 1.316203 0.02374975 subunit IB (dopamine and cAMP regulated

phosphoprotein, DARPP-32)

TSKS testis-specific serine kinase substrate 1.315893 0.00713658

KIR2DL2 killer cell immunoglobulin-like receptor, two 1.315851 0.01475652 domains, long cytoplasmic tail, 2

FAM109A family with sequence similarity 109, member A 1.315757 0.02257493

MAGEL2 #N/A 1.315658 0.04378946

PTH1R parathyroid hormone 1 receptor 1.315632 0.0486571

MYH2 myosin, heavy chain 2, skeletal muscle, adult 1.315621 0.00327681

COMMD1 copper metabolism (Murrl) domain containing 1 1.315589 0.04072324

PIWIL4 Piwi-like 4 (Drosophila) 1.315555 0.00434309

RCAN1 regulator of calcineurin 1 1.315489 0.02339676

ZEB1 zinc finger E-box binding homeobox 1 1.314865 0.04632938

MAP3K13 mitogen-activated protein kinase kinase kinase 13 1.314721 0.02698734

HDAC5 histone deacetylase 5 1.313934 0.0481495

SEMA3C sema domain, immunoglobulin domain (Ig), short 1.313924 0.04885031 basic domain, secreted, (semaphorin) 3C

SMAD6 SMAD family member 6 1.313915 0.04895342

PFT 1 PFTAIRE protein kinase 1 1.313884 0.01269846

SERPINA Serpin peptidase inhibitor, clade A (alpha- 1 1.313754 0.00679302 9 antiproteinase, antitrypsin), member 9

AC ATI acetyl-CoA acetyltransferase 1 1.313644 0.04753139

CAPN7 Calpain 7 1.313621 0.03062464

HPD #N/A 1.313449 0.04917888

NUP155 nucleoporin 155kDa 1.313273 0.0391177

MMP10 #N/A 1.313052 0.00879522

ECM2 extracellular matrix protein 2, female organ and 1.31297 0.04898875 adipocyte specific

ACTBL3 #N/A 1.31287 0.00406906

HLA- #N/A 1.312829 0.04824824 DRB5

KHSRP KH-type splicing regulatory protein 1.312595 0.03596163

APBB3 amyloid beta (A4) precursor protein-binding, 1.312555 0.03722342 family B, member 3

UGT2B28 UDP glucuronosyltransferase 2 family, 1.312459 0.04065599 polypeptide B28

WFDC12 #N/A 1.31236 0.04720783

IFT81 intraflagellar transport 81 homolog 1.312081 0.0241023

(Chlamydomonas)

ARPC1B actin related protein 2/3 complex, subunit IB, 1.311651 0.02753439

41kDa

MICAL2 microtubule associated monoxygenase, calponin 1.311573 0.01533516 and LIM domain containing 2

ZNF193 zinc finger protein 193 1.311509 0.02200133

KCNAB1 potassium voltage-gated channel, shaker-related 1.31142 0.03159023

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

subfamily, beta member 1

GRINA glutamate receptor, ionotropic, N-methyl D- 1.311403 0.03669983 aspartate-associated protein 1 (glutamate binding)

ANGPTL angiopoietin-like 6 1.31 1251 0.04023643 6

CCDC125 coiled-coil domain containing 125 1.311077 0.04961275 HMGCS1 3-hydroxy-3-methylglutaryl-CoA synthase 1 1.310916 0.01609754

(soluble)

NUS1 nuclear undecaprenyl pyrophosphate synthase 1 1.31088 0.03638989 homolog (S. cerevisiae)

ANXA8 annexin A8 1.310877 0.04901674

C8orf55 chromosome 8 open reading frame 55 1.310792 0.04199884

CREG1 cellular repressor of ElA-stimulated genes 1 1.310534 0.02867724

RCC2 regulator of chromosome condensation 2 1.309952 0.02529485

MYH13 myosin, heavy chain 13, skeletal muscle 1.309813 0.00229448

ARID 1 A AT rich interactive domain 1A (SWI-like) 1.309753 0.0241035

ST6GAL ST6 (alpha-N-acetyl-neuraminyl-2,3 -beta- 1.309637 0.00775862

NAC1 galactosyl- 1 ,3)-N-acetylgalactosaminide alpha- 2,6-sialyltransferase 1

SCGB1C1 secretoglobin, family 1C, member 1 1.30957 0.01019826

Cl lorf79 Chromosome 11 open reading frame 79 1.309097 0.02724393

GSTCD glutathione S-transferase, C-terminal domain 1.308976 0.00023955 containing

PIK3CB phosphoinositide-3-kinase, catalytic, beta 1.308634 0.03742953 polypeptide

EPRS glutamyl-prolyl-tRNA synthetase 1.308599 0.02361163 SUPT5H suppressor of Ty 5 homolog (S. cerevisiae) 1.307863 0.01749818 IL18RAP interleukin 18 receptor accessory protein 1.307668 0.0227035 SLC30A3 solute carrier family 30 (zinc transporter), member 1.307468 0.01544482

3

CDC42EP #N/A 1.306756 0.04378984 3

P2RX3 purinergic receptor P2X, ligand-gated ion channel, 1.306563 0.03962583

3

DPF1 D4, zinc and double PHD fingers family 1 1.306337 0.01809137

WT1 Wilms tumor 1 1.306117 0.03913065

C7orf52 chromosome 7 open reading frame 52 1.305718 0.00211672

ZNF622 zinc finger protein 622 1.305364 0.03391459

C4orf33 chromosome 4 open reading frame 33 1.305078 0.03778524

CLCC1 chloride channel CLIC-like 1 1.30507 0.03679493

ATP1B2 ATPase, Na+/ + transporting, beta 2 polypeptide 1.305069 0.01874

MANEAL mannosidase, endo-alpha-like 1.304964 0.03096874

COL7A1 collagen, type VII, alpha 1 1.3043 0.04893659

ZHX3 zinc fingers and homeoboxes 3 1.304281 0.00510183

RASGRF1 Ras protein-specific guanine nucleotide-releasing 1.304227 0.02912166 factor 1

ZNF215 zinc finger protein 215 1.303954 0.01264929 ZC3H11A zinc finger CCCH-type containing 11 A 1.303881 0.04908546 NEIL3 nei endonuclease VHI-like 3 (E. coli) 1.303447 0.04056936 PRODH proline dehydrogenase (oxidase) 1 1.303404 0.04779837

DB l/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P

Symbol Change value

MED25 mediator complex subunit 25 1.303334 0.03529458

CYP27A1 #N/A 1.303212 0.03372699

GFRAL #N/A 1.303147 0.00927841

CLK2 CDC-like kinase 2 1.302684 0.02715932

CDC2L1 #N/A 1.302623 0.00493949

ONECUT one cut homeobox 1 1.30261 0.02150041

1

DARS aspartyl-tRNA synthetase 1.302588 0.03877241

CPNE4 #N/A 1.302533 0.03382635

RELT RELT tumor necrosis factor receptor 1.302513 0.00307975

POU4F1 POU class 4 homeobox 1 1.302303 0.03003303

Pl l 26 serine protease 1.302277 0.01666558

AN S6 #N/A 1.30191 0.01732197

ARMET Arginine-rich, mutated in early stage tumors 1.301554 0.02325872

EXOSC9 exosome component 9 1.301209 0.02001717

GOLGA1 golgin Al 1.301101 0.00409553

MSH2 mutS homolog 2, colon cancer, nonpolyposis type 1.301052 0.00303927

1 (E. coli)

MAML3 mastermind-like 3 (Drosophila) 1.300927 0.04496825

DDX21 #N/A 1.30083 0.02404695

GPR50 G protein-coupled receptor 50 1.300636 0.03631905

TGM4 transglutaminase 4 (prostate) 1.300431 0.04895508

POLR3F polymerase (RNA) III (DNA directed) polypeptide 1.299365 0.03626355

F, 39 kDa

TMEM12 transmembrane protein 125 1.29855 0.02820931

J

DMRTC1 DMRT-like family CI 1.298315 0.01042075

PRKAB1 protein kinase, AMP-activated, beta 1 non- 1.298097 0.04325755 catalytic subunit

DHX9 DEAH (Asp-Glu-Ala-His) box polypeptide 9 1.297972 0.02876581

KRT222P Keratin 222 pseudogene 1.297831 0.03679215

YIF1A Yipl interacting factor homolog A (S. cerevisiae) 1.297603 0.03754831

TCF12 transcription factor 12 1.297588 0.0231 1339

ALPPL2 #N/A 1.297346 0.03011951

SPRY3 sprouty homolog 3 (Drosophila) 1.297167 0.04437122

MITD1 MIT, microtubule interacting and transport, 1.29714 0.03856481 domain containing 1

ITGA2 integrin, alpha 2 (CD49B, alpha 2 subunit of 1.296809 0.03941384

VLA-2 receptor)

CAP2 CAP, adenylate cyclase-associated protein, 2 1.296647 0.00235809

(yeast)

ZBTB9 zinc finger and BTB domain containing 9 1.296604 0.02182821

LIN7B lin-7 homolog B (C. elegans) 1.296549 0.01491215

PRR5 proline rich 5 (renal) 1.296011 0.03296957

KCNQ3 potassium voltage-gated channel, KQT-like 1.295465 0.00988049 subfamily, member 3

GATAD2 GATA zinc finger domain containing 2B 1.295344 0.0051653 r>

D

SLC12A3 solute carrier family 12 (sodium/chloride 1.295226 0.0361613 transporters), member 3

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

DUS3L dihydrouridine synthase 3-like (S. cerevisiae) 1.294954 0.03184389

GPR1 13 G protein-coupled receptor 113 1.294818 0.0368055

NBPF4 neuroblastoma breakpoint family, member 4 1.294176 0.03458487

GNAS GNAS complex locus 1.294113 0.02526419

HNF4A hepatocyte nuclear factor 4, alpha 1.293896 0.02932833

RAD 1 RAD1 homolog (S. pombe) 1.293558 0.0171556

UQCRQ ubiquinol-cytochrome c reductase, complex III 1.29346 0.04854268 subunit VII, 9.5kDa

CALCRL #N/A 1.293072 0.02451256

RPP14 ribonuclease P/MRP 14kDa subunit 1.293011 0.04069763

COL12A1 collagen, type XII, alpha 1 1 .29279 0.04414952

LY75 lymphocyte antigen 75 1.292702 0.0057195

PPFIA1 protein tyrosine phosphatase, receptor type, f 1.292575 0.03195209 polypeptide (PTPRF), interacting protein (liprin),

alpha 1

WDR23 WD repeat domain 23 1.292564 0.02314096 MY03B myosin IIIB 1.292237 0.03247619 LRCH2 leucine-rich repeats and calponin homology (CH) 1.292236 0.0130786 domain containing 2

ZNF578 zinc finger protein 578 1.292192 0.03081413

PDK4 pyruvate dehydrogenase kinase, isozyme 4 1.292167 0.02978736

BTN3A2 butyrophilin, subfamily 3, member A2 1.292111 0.04600277

ZNF570 zinc finger protein 570 1.291793 0.04084999

ASTN1 astrotactin 1 1.291557 0.0244782

TMEM10 transmembrane protein 101 1.291523 0.01355169

1

LEAP2 #N/A 1.290898 0.01576343

FAM46A family with sequence similarity 46, member A 1.290802 0.01962303

TRIP4 Thyroid hormone receptor interactor 4 1.290743 0.04337559

LOC4006 #N/A 1.289945 0.01369745

96

ABL1 c-abl oncogene 1 , receptor tyrosine kinase 1.289406 0.04543309

COL2A1 collagen, type II, alpha 1 1.289223 0.03761942

TBC1D1 TBCl (tre-2/USP6, BUB2, cdcl6) domain family, 1.289144 0.01925313 member 1

MY07A myosin VIIA 1.288321 0.04911618 SNHG3 small nucleolar RNA host gene 3 (non-protein 1.288272 0.00957217 coding)

S1AE sialic acid acetylesterase 1.288003 0.04485108

OR1Q1 #N/A 1.287798 0.00170856

DIP2B DIP2 disco-interacting protein 2 homolog B 1.287687 0.0218845

(Drosophila)

ARHGEF Rho guanine nucleotide exchange factor (GEF) 7 1.287534 0.0405397 7

LIPF lipase, gastric 1.287407 0.02793804 F5 coagulation factor V (proaccelerin, labile factor) 1.287381 0.01953173

OR1S1 Olfactory receptor, family 1 , subfamily S, member 1.287109 0.00690034

1

ATF5 #N/A 1.286814 0.04972411 RALGPS2 Ral GEF with PH domain and SH3 binding motif 1.286257 0.04061583

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

2

BCAN brevican 1.286146 0.03577875 Fl l coagulation factor XI 1.285686 0.02838542

GREM2 #N/A 1.285532 0.04360017

TORIAIP torsin A interacting protein 2 1.285517 0.02358602

2

GPS1 #N/A 1.285464 0.04388261 ABCA6 ATP-binding cassette, sub-family A (ABC1), 1.285056 0.03126701 member 6

HOXC12 #N/A 1.285033 0.03233783 ADPRHL ADP-ribosylhydrolase like 2 1.285009 0.04195797 2

FXYD1 #N/A 1.284826 0.04189004

CLEC5A #N/A 1.284664 0.03995698

HDGF hepatoma-derived growth factor 1.284638 0.04400985

SPOPL speckle-type POZ protein-like 1.284296 0.03378694

C17orf73 chromosome 17 open reading frame 73 1.284227 0.02929441

EBF1 #N/A 1.284106 0.04508284

DAG1 dystroglycan 1 (dystrophin-associated 1.284098 0.00984698 glycoprotein 1)

PXN paxillin 1.283966 0.04880114

ARHGAP R o GTPase activating protein 10 1.283734 0.02955473 10

B3GALT6 UDP-Gal:betaGal beta 1,3-galactosyltransferase 1.283705 0.01387262 polypeptide 6

MIDI #N/A 1.283608 0.03838221

FLJ26056 #N/A 1.283583 0.03857654

C14orfl59 chromosome 14 open reading frame 159 1.28356 0.04379116

ATAD3B ATPase family, AAA domain containing 3B 1.283442 0.0479323

IQCA1 IQ motif containing with AAA domain 1 1.282184 0.00914257

RXFP1 relaxin/insulin-like family peptide receptor 1 1.282122 0.00278521

CRYGB crystallin, gamma B 1.282066 0.02889521

ADCY10 adenylate cyclase 10 (soluble) 1.28206 0.04725498

NSUN3 #N/A 1.281746 0.04989998

DUOX2 dual oxidase 2 1.281683 0.04227892

KNDC1 kinase non-catalytic C-lobe domain (KIND) 1.280672 0.03136853 containing 1

STX1B syntaxin IB 1.280564 0.01411697 SLC4A8 solute carrier family 4, sodium bicarbonate 1.280486 0.04023173 cotransporter, member 8

RPL7L1 ribosomal protein L7-like 1 1.280321 0.0449192 DMXL2 Dmx-like 2 1.280287 0.04149996 GPR81 G protein-coupled receptor 81 1.280119 0.03239705 EIF4E3 eukaryotic translation initiation factor 4E family 1.279238 0.02679712 member 3

PRKRA protein kinase, interferon-inducible double 1.278927 0.03584581 stranded RNA dependent activator

TEX11 testis expressed 11 1.278877 0.03709168 HSPA9 heat shock 70kDa protein 9 (mortalin) 1.278665 0.01554267 PAX5 paired box 5 1.278361 0.01289398

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

CYP4X1 cytochrome P450, family 4, subfamily X, 1.27801 0.03550355 polypeptide 1

DNAH7 dynein, axonemal, heavy chain 7 1.277659 0.04289445 MAPK8IP mitogen-activated protein kinase 8 interacting 1.277633 0.03321973 3 protein 3

KLHDC9 kelch domain containing 9 1.277612 0.04814524 PCDHB17 #N/A 1.277596 0.03612841 FBX09 F-box protein 9 1.276761 0.02422462 APCDD1 #N/A 1.27674 0.03973463 MBTPS 1 membrane-bound transcription factor peptidase, 1.27672 0.04423689 site 1

GTF2I general transcription factor Hi 1.276479 0.03942891 HSPC 159 galectin-related protein 1.276374 0.0439434

MAP3K6 mitogen-activated protein kinase kinase kinase 6 1.275563 0.01955517 MRPS5 mitochondrial ribosomal protein S5 1.275511 0.01551189 CASP3 caspase 3, apoptosis-related cysteine peptidase 1.275471 0.00672259 PKN2 protein kinase N2 1.275239 0.02515919

PDE6D phosphodiesterase 6D, cGMP-specific, rod, delta 1.275132 0.01303783

RNF 144B ring finger protein 144B 1.275124 0.04620057

FAM138D #N/A 1.275058 0.03045217

C12orf52 chromosome 12 open reading frame 52 1.274935 0.04444509

MTA3 Metastasis associated 1 family, member 3 1.274622 0.03563214

MADD MAP-kinase activating death domain 1.274143 0.04855802

TRMT61 tRNA methyltransferase 61 homoiog B (S. 1.273568 0.02526202

B cerevisiae)

ZNF14 zinc finger protein 14 1.272835 0.03423005

FAM124A family with sequence similarity 124 A 1.272775 0.04168444

DIXDCl #N/A 1.2725 0.04072744

FCRL5 Fc receptor-like 5 1.272331 0.03206552

COL4A3 collagen, type IV, alpha 3 (Goodpasture antigen) 1.272118 0.02337824 SLC11 A2 solute carrier family 11 (proton-coupled divalent 1.27202 0.01701597 metal ion transporters), member 2

OR10G4 Olfactory receptor, family 10, subfamily G, 1.271988 0.02930133 member 4

NPR2 natriuretic peptide receptor B/guanylate cyclase B 1.271875 0.03567998

(atrionatriuretic peptide receptor B)

DAZ1 deleted in azoospermia 1 1.271743 0.01264477

ATP2B3 ATPase, Ca++ transporting, plasma membrane 3 1.271474 0.0447933 PI 15 peptidase inhibitor 15 1.271393 0.04151015

NSMCE2 non-SMC element 2, MMS21 homoiog (S. 1.271363 0.02515466 cerevisiae)

HYDIN hydrocephalus inducing homoiog (mouse) 1.27123 0.03905987 C 19orf51 chromosome 19 open reading frame 51 1.271156 0.0284778 STK31 serine/threonine kinase 31 1.271058 0.02681916 COPB2 coatomer protein complex, subunit beta 2 (beta 1.270956 0.02084552 prime)

SLC19A2 solute carrier family 19 (thiamine transporter), 1.270824 0.00397826 member 2

ZFP28 zinc finger protein 28 homoiog (mouse) 1.270796 0.03986652 IFNA17 #N/A 1.27064 0.00548264

DB1/ 694₃7516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P

Symbol Change value

UAP1L1 UDP-N-acteylglucosamine pyrophosphorylase 1 - 1.270479 0.0296152 like 1

GDA #N/A 1.270411 0.03882797

PRKAB2 protein kinase, AMP-activated, beta 2 non- 1.270082 0.03231 157 catalytic subunit

ZNF425 Zinc finger protein 425 1.270009 0.04598816

WWC1 WW and C2 domain containing 1 1.269983 0.04551941

ABCB1 ATP-binding cassette, sub-family B (MDR/TAP), 1.269778 0.02854381 member 1

PDCL2 phosducin-like 2 1.269367 0.00061538

C14orf39 chromosome 14 open reading frame 39 1.269251 0.01571564

OR5V1 #N/A 1.268983 0.03792536

YARS tyrosyl-tRNA synthetase 1.26819 0.01419457

RIBC2 #N/A 1.268036 0.02692288

GPR89A G protein-coupled receptor 89A 1.267631 0.02533276

PARVA parvin, alpha 1.267495 0.02553094

LYPD6 LY6/PLAUR domain containing 6 1.267092 0.04639769

CASQ2 #N/A 1.267042 0.00722503

ARFIP1 ADP-ribosylation factor interacting protein 1 1.266696 0.04164397

NUP88 nucleoporin 88kDa 1.266061 0.04223257

PLXNA4 Plexin A4 1.26585 0.02073357

DNAH8 dynein, axonemal, heavy chain 8 1.265201 0.00013086

BUB1 budding uninhibited by benzimidazoles 1 homolog 1.26498 0.04131477

(yeast)

HSPA12B heat shock 70kD protein 12B 1.264936 0.03344558

AN RD1 ankyrin repeat domain 12 1.26444 0.03384275 z

AP2A1 adaptor-related protein complex 2, alpha 1 subunit 1.26436 0.04642281

ATIC 5 -aminoimidazole-4-carboxamide ribonucleotide 1.264237 0.03857019 formyltransferase/IMP cyclohydrolase

MYOCD myocardin 1.264143 0.01117924

TRIM36 tripartite motif-containing 36 1.263855 0.04894895

KIAA019 KIAA0195 1.263548 0.04435687

J

MRPS25 Mitochondrial ribosomal protein S25 1.26347 0.01791241

PCDHGC protocadherin gamma subfamily C, 5 1.263433 0.04118921

•

PRPF39 PRP39 pre-mRNA processing factor 39 homolog 1.263236 0.03313913

(S. cerevisiae)

IP09 importin 9 1.262536 0.03239699

BCAS3 Breast carcinoma amplified sequence 3 1.262477 0.01277402

METTL4 #N/A 1.262252 0.01031767

MAP3K11 mitogen-activated protein kinase kinase kinase 11 1.262091 0.02976909

FAM92A1 family with sequence similarity 92, member Al 1.262032 0.04147755

ZNF781 zinc finger protein 781 1.261777 0.00937657

PPM IF protein phosphatase, Mg2+/Mn2+ dependent, IF 1.261501 0.00705184

CCDC52 coiled-coil domain containing 52 1.261425 0.01610132

PC pyruvate carboxylase 1.261405 0.00486587

GGTA1 glycoprotein, alpha-galactosyltransferase 1 1.261257 0.00876746 pseudogene

DB1/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

RHBDD2 rhomboid domain containing 2 1.260801 0.00848564

VSTM1 #N/A 1.26072 0.04402841

TNNI3K TN I3 interacting kinase 1.2606 0.04011763

GLIS3 GLIS family zinc finger 3 1.260323 0.01659638

ZNF613 zinc finger protein 613 1.258929 0.00352566

CXorf40A chromosome X open reading frame 40A 1.258447 0.01336367

KIF21A kinesin family member 21 A 1.257661 0.01839864

RILP Rab interacting lysosomal protein 1.257525 0.0052284

TRIM58 tripartite motif-containing 58 1.257469 0.04056475

PTPRA protein tyrosine phosphatase, receptor type, A 1.257443 0.02131531

TAGAP T-cell activation GTPase activating protein 1.256328 0.01003539

MCM3 minichromosome maintenance complex 1.256221 0.01483353 component 3

GIPC2 GIPC PDZ domain containing family, member 2 1.255826 0.03658988

POLR3E polymerase (RNA) III (DNA directed) polypeptide 1.2556 0.0032588

E (80kD)

PPP 1 R 10 protein phosphatase 1 , regulatory (inhibitor) 1.255596 0.04773474 subunit 10

SNX27 sorting nexin family member 27 1.255409 0.02661206

ABCF2 ATP-binding cassette, sub-family F (GCN20), 1.254928 0.00078914 member 2

NT5DC1 5'-nucleotidase domain containing 1 1.254258 0.03833736

ZFX #N/A 1.254057 0.02842691

TNKS 1BP tankyrase 1 binding protein 1, 182kDa 1.254051 0.0267223 1

CP1 10 CP110 protein 1.253971 0.02752672

PASD1 PAS domain containing 1 1.253623 0.00725862

PQLC2 PQ loop repeat containing 2 1.253527 0.0481956

TPCN1 two pore segment channel 1 1.253329 0.02771144

POM121 POM121 membrane glycoprotein (rat) 1.25332 0.04289457

STRBP spermatid perinuclear RNA binding protein 1.253091 0.02912347

COASY CoA synthase 1.252781 0.04184411

RAF1 v-raf-1 murine leukemia viral oncogene homolog 1.252769 0.02889318

1

CPSF3 cleavage and polyadenylation specific factor 3, 1.252728 0.01347429

73kDa

PDGFRB platelet-derived growth factor receptor, beta 1.2526 0.01825528 polypeptide

OR11L1 Olfactory receptor, family 11, subfamily L, 1.252538 0.03151985 member 1

MAP2K3 mitogen-activated protein kinase kinase 3 1.252382 0.01292775

MAGEC2 melanoma antigen family C, 2 1.251806 0.04643824

HRASLS HRAS-like suppressor 1.251591 0.01555165

HNF4G #N/A 1.251585 0.04917062

TD02 tryptophan 2,3 -dioxygenase 1.251091 0.01531997

TFG TRK-fused gene 1.251084 0.02019895

MAT2B methionine adenosyltransferase II, beta 1.250962 0.00601561

ERAP2 endoplasmic reticulum aminopeptidase 2 1.250556 0.02769817

LIMCH1 LIM and calponin homology domains 1 1.24951 0.03223645

COL4A4 collagen, type IV, alpha 4 1.249353 0.03545571

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

FAM86C family with sequence similarity 86, member C 1.249117 0.03879044 ASGR2 asialoglycoprotein receptor 2 1.249028 0.04655806 TOM1 target of mybl (chicken) 1.248495 0.01800626 DAB2 disabled homolog 2, mitogen-responsive 1.248421 0.03947221 phosphoprotein (Drosophila)

EHBP1 EH domain binding protein 1 1.248177 0.03923267 COPS4 COP9 constitutive photomorphogenic homolog 1.247876 0.04658872 subunit 4 (Arabidopsis)

MMP3 #N/A 1.246785 0.01655688 TANK TRAF family member-associated NFKB activator 1.24674 0.02488358 AKT2 v-akt murine thymoma viral oncogene homolog 2 1.246722 0.01259013 ATF4 activating transcription factor 4 (tax-responsive 1.246548 0.00900501 enhancer element B67)

ADAMTS ADAMTS-like 3 1.246259 0.02218159 L3

RNASEH ribonuclease H2, subunit B 1.245775 0.04827555 2B

KIAA126 KIAA1267 1.245732 0.04533407 7

MIOS missing oocyte, meiosis regulator, homolog 1.245244 0.03115889

(Drosophila)

FAM84B family with sequence similarity 84, member B 1.245212 0.03957666 GNPTAB N-acetylglucosamine- 1 -phosphate transferase, 1.244249 0.02637465 alpha and beta subunits

C7orf28A chromosome 7 open reading frame 28A 1.244241 0.01136235

FGL1 fibrinogen-like 1 1.243607 0.03424585

FDPS farnesyl diphosphate synthase (farnesyl 1.243357 0.01230338 pyrophosphate synthetase,

dimethylallyltranstransferase,

geranyltranstransferase)

HCCS #N/A 1.243197 0.04454228 EIF4EBP1 eukaryotic translation initiation factor 4E binding 1.242901 0.03329666 protein 1

GLMN glomulin, FKBP associated protein 1.242806 0.01074317 SLC36A3 solute carrier family 36 (proton/amino acid 1.242714 0.03471447 symporter), member 3

HR Hairless homolog (mouse) 1.242273 0.01561571

CACNA1 #N/A 1.24211 0.01850723 F

FLJ38723 hypothetical FLJ38723 1.241923 0.01852625

ZNF143 zinc finger protein 143 1.241752 0.03860238

SUZ12 suppressor of zeste 12 homolog (Drosophila) 1.241237 0.04277373

PON3 paraoxonase 3 1.2403 0.01155334

C14orf21 #N/A 1.2401 19 0.03267246

HTR3B #N/A 1.239835 0.03170828

FBXL4 F-box and leucine-rich repeat protein 4 1.239726 0.03680803

MIB1 mindbomb homolog 1 (Drosophila) 1.239452 0.03698461

ZHX2 zinc fingers and homeoboxes 2 1.239388 0.00501939

NDST4 N-deacetylase/N-sulfotransferase (heparan 1.239191 0.02903312 glucosaminyl) 4

DB l/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

VWA1 #N/A 1.239135 0.01162727

PRKAR1 protein kinase, cAMP-dependent, regulatory, type 1.23851 0.00312229

A I, alpha (tissue specific extinguisher 1)

NCOA7 nuclear receptor coactivator 7 1.237865 0.00128132 GBP6 guanylate binding protein family, member 6 1.237788 0.03008652 CALCOC calcium binding and coiled-coil domain 1 1.237698 0.04981056 01

AKNA AT-hook transcription factor 1.237234 0.03152078

AN02 anoctamin 2 1.236902 0.04959632

COL17A1 collagen, type XVII, alpha 1 1.236684 0.0447795

GLT1D1 #N/A 1.236359 0.03506938

C7orf53 #N/A 1.235726 0.04031539

PANK2 Pantothenate kinase 2 (Hallervorden-Spatz 1.235141 0.03673737 syndrome)

RPSAP52 ribosomal protein SA pseudogene 52 1.234438 0.02712198

LCE4A #N/A 1.234144 0.01137053

TAF7 TAF7 RNA polymerase II, TATA box binding 1.233448 0.04085823 protein (TBP)-associated factor, 55kDa

KIF5C kinesin family member 5 C 1.232486 0.03748713 WNT2 wingless-type MMTV integration site family 1.232331 0.01137624 member 2

NCKAP1 NCK-associated protein 1 -like 1.231943 0.04050152 L

LOC4420 hypothetical LOC442028 1.231005 0.02574421 28

MUC21 mucin 21 , cell surface associated 1.230888 0.00636689 ZNF280B zinc finger protein 280B 1.22931 0.04300624 RU DC3 RUN domain containing 3A 1.229173 0.01050238 A

DHRS7 dehydrogenase/reductase (SDR family) member 7 1.228972 0.02059347 CEP 120 centrosomal protein 120kDa 1.228739 0.04280283 ZNF740 zinc finger protein 740 1.228139 0.0448329 BXDC5 Brix domain containing 5 1.228102 0.02902991 APITD1 apoptosis-inducing, TAF9-like domain 1 1.227749 0.0267092 IKBKB inhibitor of kappa light polypeptide gene enhancer 1.22676 0.0218311 in B-cells, kinase beta

LSP1 lymphocyte-specific protein 1 1.226601 0.02056225

ACACB acetyl-CoA carboxylase beta 1.226541 0.04957428

PARL presenilin associated, rhomboid-like 1.226446 0.0367682

GJA5 gap junction protein, alpha 5, 40kDa 1.226313 0.03889361

L3MBTL l(3)mbt-like (Drosophila) 1.225892 0.01802015

WDSOF1 WD repeats and SOF1 domain containing 1.225379 0.01660816

NFKBIB nuclear factor of kappa light polypeptide gene 1.224185 0.03315169 enhancer in B-cells inhibitor, beta

IFRD1 interferon-related developmental regulator 1 1.223621 0.0461768

RBMY1A RNA binding motif protein, Y-linked, family 1, 1.223569 0.04076852

1 member Al

GPRIN3 #N/A 1.223357 0.04888478

LOCIOOI hypothetical protein LOC100129608 1.223183 0.01528767

29608

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

ARID IB AT rich interactive domain IB (SWIl-like) 1.223178 0.02072647 SPOCK3 sparc/osteonectin, cwcv and kazal-like domains 1.222704 0.02605689 proteoglycan (testican) 3

RNASEH ribonuclease HI 1.22204 0.02031113 1

BHLHE22 basic helix -loop-helix family, member e22 1.221705 0.04813503 PTK6 PTK6 protein tyrosine kinase 6 1.221542 0.02077182 CRISPl cysteine-rich secretory protein 1 1.221404 0.04691411 PSMD3 proteasome (prosome, macropain) 26S subunit, 1.220652 0.04587661 non-ATPase, 3

IRS2 insulin receptor substrate 2 1.219897 0.01398234

PTGER4 #N/A 1.21928 0.00509381

USP9Y ubiquitin specific peptidase 9, Y-linked 1.219224 0.01601733

ACADVL acyl-CoA dehydrogenase, very long chain 1.218665 0.03752542

CHL1 cell adhesion molecule with homology to LI CAM 1.218548 0.0364314

(close homolog of LI)

RIMS2 regulating synaptic membrane exocytosis 2 1.218523 0.00582967

ADAM22 ADAM metallopeptidase domain 22 1.218147 0.04977676

PMS1 PMS1 postmeiotic segregation increased 1 (S. 1.217981 0.03860087 cerevisiae)

KIF1A kinesin family member 1 A 1.21752 0.00196066 X R6 XK, Kell blood group complex subunit-related 1.21749 0.04322222 family, member 6

USP7 ubiquitin specific peptidase 7 (herpes virus- 1.2173 0.03971564 associated)

TRHDE #N/A 1.216856 0.01790775

GAS2L2 growth arrest-specific 2 like 2 1.216707 0.00746077

SCAND3 SCAN domain containing 3 1.216047 0.04952198

MOCS2 molybdenum cofactor synthesis 2 1.215847 0.04158688

PYGB phosphorylase, glycogen; brain 1.214217 0.04721694

CDC26 Cell division cycle 26 homolog (S. cerevisiae) 1.214154 0.04346382

PLSCR1 phospholipid scramblase 1 1.213882 0.04871947

IMPG1 interphotoreceptor matrix proteoglycan 1 1.212979 0.02801435

MMP8 matrix metallopeptidase 8 (neutrophil collagenase) 1.212836 0.01042643

SMARCA SWI/SNF related, matrix associated, actin 1.212641 0.01091184

5 dependent regulator of chromatin, subfamily a,

member 5

FAM182A #N/A 1.212618 0.03154097

NIN ninein (GSK3B interacting protein) 1.212281 0.03559446

NTRK3 neurotrophic tyrosine kinase, receptor, type 3 1.211585 0.03948024

PPA2 pyrophosphatase (inorganic) 2 1.21132 0.04234664

RG9MTD RNA (guanine-9-) methyltransferase domain 1.210992 0.00622261

3 containing 3

ALDH16 aldehyde dehydrogenase 16 family, member Al 1.210101 0.03869864

Al

IL9R interleukin 9 receptor 1.210046 0.04769692

NSMCE4 non-SMC element 4 homolog A (S. cerevisiae) 1.209717 0.03610428

A

NEXN nexilin (F actin binding protein) 1.209156 0.01265075 SOX30 SRY (sex determining region Y)-box 30 1.208577 0.03233023

DBl/ 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

SYN2 synapsin ll 1.20705 0.02188363

FAM136A #N/A 1.206366 0.02512492

UBAP2L ubiquitin associated protein 2-like 1.205878 0.04256504

TAGLN3 transgelin 3 1.204673 0.01504545

KCNH2 potassium voltage-gated channel, subfamily H 1.204637 0.04732818

(eag-related), member 2

DE ND4 DENN/MADD domain containing 4A 1.204522 0.03533718 A

RBM38 RNA binding motif protein 38 1.204225 0.02843861

C14orf53 #N/A 1.203751 0.04928678

DDX1 DEAD (Asp-Glu-Ala-Asp) box polypeptide 1 1.203182 0.04887201

METTL8 methyltransferase like 8 1.203141 0.04296381

RABEP1 rabaptin, RAB GTPase binding effector protein 1 1.202797 0.0453199

CYLC2 cylicin, basic protein of sperm head cytoskeleton 2 1.202599 0.03060352

CLCA4 chloride channel accessory 4 1.201348 0.03271975

SLC22A2 solute carrier family 22 (organic cation 1.200369 0.04640189 transporter), member 2

CREB1 cAMP responsive element binding protein 1 1.199173 0.02092548

CCDC74 coiled-coil domain containing 74A 1.197072 0.03380953

A

RPL35 ribosomal protein L35 1.196344 0.03583088 C16orf89 chromosome 16 open reading frame 89 1.195652 0.03712854 GYLTL1 glycosyltransferase-like IB 1.195435 0.01664133 B

CRTAP cartilage associated protein 1.194501 0.01415943

AR T aryl hydrocarbon receptor nuclear translocator 1.194489 0.03711559

PPP1CB protein phosphatase 1 , catalytic subunit, beta 1.194031 0.01004224 isozyme

ACVR2A activin A receptor, type IIA 1.194004 0.04361939 CYP11B2 cytochrome P450, family 11, subfamily B, 1.193589 0.04786336 polypeptide 2

C5orfl3 chromosome 5 open reading frame 13 1.193585 0.04570836 C3orf57 chromosome 3 open reading frame 57 1.192686 0.04563884 PLD5 #N/A 1.192032 0.01557073 DBI diazepam binding inhibitor (GABA receptor 1.191704 0.03345418 modulator, acyl-CoA binding protein)

KLF2 #N/A 1.19143 0.02001404

RPL13AP #N/A 1.190779 0.03599393

5

C17orf80 chromosome 17 open reading frame 80 1.18979 0.02904241

THEM4 thioesterase superfamily member 4 1.189005 0.04797765

DNAJC12 #N/A 1.186992 0.03956968

KIAA019 KIAA0196 1.185084 0.01295962

6

MTERFD #N/A 1.184715 0.02707179 1

NMD3 NMD3 homolog (S. cerevisiae) 1.184712 0.03234417

RNF220 ring finger protein 220 1.182256 0.01184286

PRKAR2 protein kinase, cAMP-dependent, regulatory, type 1.182192 0.02527208

A II, alpha

DBV 69437516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P Symbol Change value

MYOZ3 myozenin 3 1.181691 0.01236801

CHCHD3 coiled-coil-helix-coiled-coil-helix domain 1.181329 0.02752 containing 3

GLI1 GLI family zinc finger 1 1.1812 0.04533189

RHEB Ras homolog enriched in brain 1.181134 0.04261909

AGPAT5 1 -acylglycerol-3 -phosphate O-acyltransferase 5 1.180946 0.04081501

(lysophosphatidic acid acyltransferase, epsilon)

N4BP1 NEDD4 binding protein 1 1.180702 0.04692864

L3MBTL2 l(3)mbt-like 2 (Drosophila) 1.180026 0.0299198

ADAM30 ADAM metallopeptidase domain 30 1.179 0.04990268

SHPRH SNF2 histone linker PHD RING helicase 1.178229 0.00451453

SMARCA SWI/SNF related, matrix associated, actin 1.177293 0.013042 1 dependent regulator of chromatin, subfamily a,

member 1

TOMM70 translocase of outer mitochondrial membrane 70 1.176887 0.03478562 A homolog A (S. cerevisiae)

TMEM50 transmembrane protein 5 OA 1.174488 0.04619627

A

RPL14 ribosomal protein L14 1.174045 0.03528184

MMP 13 matrix metallopeptidase 13 (collagenase 3) 1.173405 0.01212002

SNRK SNF related kinase 1.173346 0.01573733

CCDC7 coiled-coil domain containing 7 1.171795 0.01953617

GIMAP8 GTPase, IMAP family member 8 1.171424 0.04639992

UTP20 UTP20, small subunit (SSU) processome 1.1711 0.02999942 component, homolog (yeast)

SCAPER S-phase cyclin A-associated protein in the ER 1.170871 0.03165583

CDH6 cadherin 6, type 2, K-cadherin (fetal kidney) 1.170618 0.04588459

TFPI tissue factor pathway inhibitor (lipoprotein- 1.170572 0.03900407 associated coagulation inhibitor)

C6orfl25 Chromosome 6 open reading frame 125 1.170359 0.01194836

UBE3B ubiquitin protein ligase E3B 1.169829 0.01247029

C12orfl0 chromosome 12 open reading frame 10 1.169491 0.03108954

RAD50 RAD50 homolog (S. cerevisiae) 1.168972 0.04507372

SRRT serrate RNA effector molecule homolog 1.168708 0.04933513

(Arabidopsis)

DNTT deoxynucleotidyltransferase, terminal 1.168405 0.02438835

C6orfl 82 Chromosome 6 open reading frame 182 1.167525 0.0089801

UGT2A1 UDP glucuronosyltransferase 2 family, 1.167157 0.00153427 polypeptide Al

RPL27A ribosomal protein L27a 1.16714 0.03286277

C9orf86 chromosome 9 open reading frame 86 1.166704 0.00822025

ZBTB7A zinc finger and BTB domain containing 7A 1.166621 0.00152025

CISD2 CDGSH iron sulfur domain 2 1.165899 0.02019682

ITGB4 integrin, beta 4 1.164572 0.04837165

C10orf53 chromosome 10 open reading frame 53 1.161286 0.03491949

GLOl glyoxalase l 1.160551 0.04744756

SLC15A1 solute carrier family 15 (oligopeptide transporter), 1.159201 0.04679593 member 1

GMCL1 germ cell-less homolog 1 (Drosophila) 1.158554 0.03783874

DNAJB11 DnaJ (Hsp40) homolog, subfamily B, member 11 1.158226 0.03171122

DB1/ 694₃7516.1 Supplemental Table 2 Gene Transcripts Upregulated by Ketones in MCF7 Cells

Gene Gene Description Fold Ttest P

Symbol Change value

USOl USOl vesicle docking protein homolog (yeast) 1.157228 0.03036641

PSMD1 proteasome (prosome, macropain) 26S subunit, 1.156795 0.03019009 non-ATPase, 1

SLFN12 #N/A 1.153905 0.02544823

HDDC2 HD domain containing 2 1.153537 0.00641685

ST6GAL1 ST6 beta-galactosamide alpha-2,6-sia]yltranferase 1.152772 0.03156348

1

TJAP1 tight junction associated protein 1 (peripheral) 1.152616 0.01205789

KEL Kell blood group, metallo-endopeptidase 1.152594 0.0401423

TSC22D1 TSC22 domain family, member 1 1.152544 0.04055428

LZIC leucine zipper and CTNNBIP 1 domain containing 1.152433 0.01022804

ATG3 ATG3 autophagy related 3 homolog (S. cerevisiae) 1.151769 0.04771406

PI 3CD phosphoinositide-3 -kinase, catalytic, delta 1.150789 0.03397076 polypeptide

Supplemental Table 3. Cellular Processes Increased in MCF7 Cells Treated with Lactate or Ketones.

Data Set P-value Detailed Description

1. Lactate-Specific Genes

Stem Cells

Enriched in mouse neural stem cells, compared to differentiated

STEMCELL NEURAL UP 1.31E-13 brain

Enriched in mouse embryonic stem cells, compared to differentiated brain and bone

STEMCELL EMBRYONIC UP 3.60E-08 marrow cells

DNA Damage

Down-regulated at any timepoint following treatment of XPB/TTD fibroblasts with 3

UVC TTD ALL DN 2.83E-07 J/m^A2 UVC

Down-regulated at any timepoint following treatment of XPB/CS fibroblasts with 3

UVC XPCS ALL DN 7.98E-07 J/m^A2 UVC

Down-regulated at 8 hours following treatment of XPB/CS

UVC XPCS 8HR DN 1.94E-06 fibroblasts with 3 J/m^A2 UVC

Down-regulated at 4 hours following treatment of

XPB/TTD fibroblasts with 3

UVC TTD 4HR DN 2.93E-06 J/m^A2 UVC

Down-regulated at any timepoint following treatment of both XPB/CS and XPB/TTD

UVC_TTD-XPCS_COMMON_DN 4.98E-05 fibroblasts with 3 J/m^A2 UVC UVC HIGH ALL DN 1.24E-03 Down-regulated at any

DBl/ 69437516.1 Supplemental Table 3. Cellular Processes Increased in MCF7 Cells Treated with Lactate or Ketones.

Data Set P-value Detailed Description

timepoint following treatment of WS1 human skin fibroblasts with UVC at a high dose (50 J/m^A2) (clusters dl-d9)

Key Transcription Factors

Neighborhood of HDAC2 histone deacetylase 2 in the

MORF HDAC2 219 3.11 E-06 MORF expression compendium

Genes with promoter regions [- 2kb,2kb] around transcription start site containing the motif GGGAGGRR which matches annotation for MAZ: MYC- associated zinc finger protein (purine-binding transcription

GGGAGGRR_V$MAZ_Q6 1.02E-04 factor)

Genes with promoter regions [- 2kb,2kb] around transcription start site containing the motif SCGGAAGY which matches annotation for ELK1: ELK1 , member of ETS oncogene

SCGGAAGY V$ELK1 02 1.47E-04 family

Genes with promoter regions [- 2kb,2kb] around transcription start site containing the motif TTTSGCGSG which matches annotation for E2F<br> TFDP1 : transcription factor Dp-

V$E2F1_Q4_01 3.28E-04 1

Genes with promoter regions [- 2kb,2kb] around transcription start site containing the motif TTGTTT which matches annotation for MLLT7:

myeloid/lymphoid or mixed- lineage leukemia (trithorax

TTGTTT_V$FOX04 homolog, Drosophila);

01 3.72E-04 translocated to, 7

Genes with promoter regions [- 2kb,2kb] around transcription start site containing the motif GGGCGGR which matches annotation for SP1: Spl

GGGCGGR_V$SP1_Q6 3.75 E-04 transcription factor

Cancer Prognosis (Poor

Survival)

Genes overexpressed in TACI low patients (poor prognosis in

MOREAUX TACI HI VS LOW DN 1.43E-04 multiple myeloma)

1/ 69437516.1 ^_ _ _ - Supplemental Table 3. Cellular Processes Increased in MCF7 Cells Treated with Lactate or Ketones.

Data Set P-value Detailed Description

Genes highly expressed in

HCC SURVIVAL GOOD VS POOR D hepatocellular carcinoma with N poor survival.

2. Ketone-Specific Genes

Stem Cells

Enriched in mouse

hematopoietic stem cells,

STEMCELL HEMA compared to differentiated brain

TOPOIETIC_UP and bone marrow

Key Transcription Factors

Genes with promoter regions [- 2kb,2kb] around transcription start site containing the motif CAGGTG which matches annotation for TCF3:

transcription factor 3 (E2A immunoglobulin enhancer

CAGGTG_V$E12_Q6 7.97E-05 binding factors E 12/E47)

Genes with promoter regions [- 2kb,2kb] around transcription start site containing the motif TGACAGNY which matches annotation for MEIS1: Meisl, myeloid ecotropic viral integration site 1 homolog

TGACAGNY V$MEIS1 01 3.33E-04 (mouse)

Genes with promoter regions [- 2kb,2kb] around transcription start site containing the motif GGGTGGRR which matches annotation for PAX4: paired

GGGTGGRR V$PAX4 03 4.16E-04 box gene 4

Neighborhood of ATF2 activating transcription factor 2 in the MORF expression MORF ATF2 258 8.02E-04 compendium

3. Common Intersecting Genes (Upregulated by both Lactate and Ketones)

DNA Damage

Down-regulated at any timepoint following treatment of XPB/CS fibroblasts with 3

UVC XPCS ALL DN 2.60E-13 J/m^A2 UVC

Down-regulated at 8 hours following treatment of XPB/CS

UVC XPCS 8HR DN 7.33E-12 fibroblasts with 3 J/m^A2 UVC

Down-regulated at any timepoint following treatment of XPB/TTD fibroblasts with 3

UVC TTD ALL DN 2.47E-08 J/m^A2 UVC

UVC XPCS 4HR DN 3.21E-07 Down-regulated at 4 hours

DBl/ 69437516.1 ^{~~ ~} Supplemental Table 3. Cellular Processes Increased in MCF7 Cells Treated with Lactate or Ketones.

Data Set P-value Detailed Description

following treatment of XPB/CS fibroblasts with 3 J/m^A2 UVC Down-regulated at 4 hours following treatment of

XPB/TTD fibroblasts with 3

UVC TTD 4HR DN 3.38E-07 J/m^A2 UVC

Downregulated by UV-B light in normal human epidermal

UVB NHEK1 DN 2.68E-06 keratinocytes

Down-regulated at 8 hours following treatment of

XPB/TTD fibroblasts with 3

UVC TTD 8HR DN 1.27E-05 J/m^A2 UVC

Down-regulated at any timepoint following treatment of both XPB/CS and XPB/TTD

UVC TTD-XPCS COMMON DN 6.54E-04 fibroblasts with 3 J/m^A2 UVC

Regulated by UV-B light in normal human epidermal

UVB_NHEK3_C5 9.27E-04 keratinocytes, cluster 5

Stem Cells

Enriched in mouse embryonic stem cells, compared to differentiated brain and bone

STEMCELL EMBRYONIC UP 7.26E-08 marrow cells

Enriched in mouse neural stem cells, compared to differentiated

STEMCELL NEURAL UP 1.29E-07 brain and bone marrow cells

Enriched in mouse

hematopoietic stem cells, compared to differentiated brain

STEMCELL HEMATOPOIETIC UP 2.93E-06 and bone marrow

Key Transcription Factors

Genes with promoter regions [- 2kb,2kb] around transcription start site containing the motif GGGCGGR which matches annotation for SP1: Spl

GGGCGGR_V$SP1_Q6 1.16E-07 transcription factor

Genes with promoter regions [- 2kb,2kb] around transcription start site containing the motif CAGGTG which matches annotation for TCF3:

transcription factor 3 (E2A immunoglobulin enhancer

CAGGTG_V$E12_Q6 1.30E-06 binding factors E12/E47)

Genes with promoter regions [- 2kb,2kb] around transcription

TGGAAA V$NFAT Q4 01 6.09E-06 start site containing the motif

DBl/ 69437516.1 ^{~ - _} Supplemental Table 3. Cellular Processes Increased in MCF7 Cells Treated with Lactate or Ketones.

Data Set P-value Detailed Description

TGGAAA which matches annotation for NFAT<br> NFATC

Genes with promoter regions [- 2kb,2kb] around transcription start site containing the motif CTTTGT which matches annotation for LEF1: lymphoid

CTTTGT_V$LEF 1 Q2 1.61E-05 enhancer-binding factor 1

Genes with promoter regions [- 2kb,2kb] around transcription start site containing the motif TTGTTT which matches annotation for MLLT7:

myeloid/lymphoid or mixed- lineage leukemia (trithorax homolog, Drosophila);

TTGTTT_V$FOXO4_01 7.86E-05 translocated to, 7

Cancer Associated Genes

Genes whose expression is consistently negatively correlated with estrogen receptor status in breast cancer - higher expression is associated

BRCA ER NEG 3.48E-04 with ER-negative tumors

Genes whose expression is consistently positively correlated with estrogen receptor status in breast cancer - higher expression is associated

BRCAJER POS 6.77E-04 with ER-positive tumors

Cancer related genes involved BRENTANI SIGNALING 1.05E-03 in the cell signaling

Supplemental Table 4: Gene Transcripts Up regulated by Lactate in MCF7 Cells that are in Common with Neural Stem Cells

Fold Ttest P

Gene Symbol Gene Description Change value

ubiquitin-conjugating enzyme E2D 2

UBE2D2 (UBC4/5 homolog, yeast) 11.637619 0.00544828

SRP19 signal recognition particle 19kDa 8.965928 0.00278124

EIF5B eukaryotic translation initiation factor 5B 8.853053 0.04053256

RAPIA RAPIA, member of RAS oncogene family 4.430772 0.01890408

CHMP2B chromatin modifying protein 2B 6.857511 0.03281982

PRDX1 peroxiredoxin 1 6.15612 0.02465945

SMC4 structural maintenance of chromosomes 4 4.707114 0.03654239

Rho-associated, coiled-coil containing

ROCK2 protein kinase 2 5.852909 0.03308627

DBl/ 69437516.1 Supplemental Table 4: Gene Transcripts Up regulated by Lactate in MCF7 Cells that are in Common with Neural Stem Cells

Fold Ttest P

Gene Symbol Gene Description Change value

BCLAF1 BCL2-associated transcription factor 1 5.819574 0.00240797 ubiqui tin-conjugating enzyme E2D 3

UBE2D3 (UBC4/5 homolog, yeast) 5.713108 0.02114428

METTL5 methyltransferase like 5 4.101808 0.01369737

CCNG1 cyclin Gl 5.586583 0.01011364

YBX1 Y box binding protein 1 5.455093 0.00261863

NMD3 NMD3 homolog (S. cerevisiae) 5.436879 0.00447774

MTDH metadherin 5.228131 0.01520368

LXN latexin 5.025051 0.00486952

H3F3A H3 histone, family 3 A 5.188202 0.0162106

SPAST spastin 5.161775 6.01E-05

PPIG peptidylprolyl isomerase G (cyclophilin G) 5.060878 0.04469338

SNX2 sorting nexin 2 4.989412 0.03586009

DEAD (Asp-Glu-Ala-Asp) box polypeptide

DDX46 46 4.96017 0.03654288

SWI/SNF related, matrix associated, actin

dependent regulator of chromatin, subfamily

SMARCA5 a, member 5 4.842003 0.0187601 protein phosphatase 1, catalytic subunit, beta

PPPICB isozyme 2.468217 0.04691501 LRPPRC leucine-rich PPR-motif containing 4.564774 0.04328232

KDEL (Lys-Asp-Glu-Leu) endoplasmic

KDELR2 reticulum protein retention receptor 2 3.368323 0.04949704

ASF1 anti-silencing function 1 homolog A

ASF1A (S. cerevisiae) 4.469944 0.01353041

IVNS1ABP influenza virus NS 1 A binding protein 4.458858 0.04032226

NIPBL Nipped-B homolog (Drosophila) 4.448285 0.02143111

P pinin, desmosome associated protein 4.433149 0.00780293

TCERG1 transcription elongation regulator 1 3.545678 0.04063693

TOP2B topoisomerase (DNA) II beta 180kDa 2.823094 0.02218412

ZMYM4 zinc finger, MYM-type 4 4.267182 0.01393137

SFRS3 splicing factor, arginine/serine-rich 3 2.716461 0.03522487

LAPTM4A lysosomal protein transmembrane 4 alpha 4.093129 0.00222108 translocated promoter region (to activated

TPR MET oncogene) 4.08363 0.00433995 CCNI cyclin I 4.045976 0.02394342 proteasome (prosome, macropain) 26S

PSMD1 subunit, non-ATPase, 1 4.011931 0.00720011 proteasome (prosome, macropain) 26S

PSMC2 subunit, ATPase, 2 3.987502 0.00426193 RWDD4A RWD domain containing 4A 3.882013 0.02249924

Rho-associated, coiled-coil containing

ROCK1 protein kinase 1 3.257404 0.01235219 NOP58 NOP58 ribonucleoprotein homolog (yeast) 3.788493 0.00288593 EPHB4 EPH receptor B4 3.78501 1 0.02475939 EPRS glutamyl-prolyl-tRNA synthetase 2.662763 0.04513234 protein tyrosine phosphatase type IVA,

PTP4A1 member 1 2.270167 0.00847749 ABCE1 ATP-binding cassette, sub-family E (OABP), 1.937131 0.02691982

DBl/ 69437516.1 Supplemental Table 4: Gene Transcripts Upregulated by Lactate in MCF7 Cells that are in Common with Neural Stem Cells

Fold Ttest P

Gene Symbol Gene Description Change value

member 1

protein kinase, cAMP-dependent, regulatory,

PRKAR1A type I, alpha (tissue specific extinguisher 1) 3.700851 0.00533686 mitogen-activated protein kinase kinase

MAP4K3 kinase kinase 3 3.183468 0.02370712 chromodomain helicase DNA binding

CHD1 protein 1 2.27918 0.02465009

MY06 myosin VI 1.499933 0.04628552

BIRC6 baculoviral IAP repeat-containing 6 3.656537 0.01040232

FIP1L1 FIP1 like 1 (S. cerevisiae) 3.647902 0.0419402

UGDH UDP-glucose 6-dehydrogenase 3.642483 0.02673765

HDLBP high density lipoprotein binding protein 1.923995 0.0317557 acyl-CoA dehydrogenase, C-4 to C-12

ACADM straight chain 3.582422 0.04333075

RFWD2 ring finger and WD repeat domain 2 3.566507 0.03374643

TXNDC9 thioredoxin domain containing 9 3.559682 0.02318797 far upstream element (FUSE) binding protein

FUBP1 1 2.584276 0.02883731 DLD dihydrolipoamide dehydrogenase 3.54755 0.03042714 FBXW11 F-box and WD repeat domain containing 11 3.538266 0.01890564 HSPA4 heat shock 70kDa protein 4 3.534902 0.02613913 chaperonin containing TCP1, subunit 6A

CCT6A (zeta 1) 2.226682 0.02645749 guanine nucleotide binding protein-like 2

GNL2 (nucleolar) 3.497915 0.01416406

ZNF259 zinc finger protein 259 3.457681 0.04340342

RANBP9 RAN binding protein 9 3.400619 0.00125475

TCEA1 transcription elongation factor A (SII), 1 3.391912 0.03816125

PPID peptidylprolyl isomerase D 3.355162 0.01495089

RNF8 ring finger protein 8 3.3143 0.00922491

SWI/SNF-related, matrix-associated actin- dependent regulator of chromatin, subfamily

SMARCAD1 a, containing DEAD/H box 1 3.284105 0.04696085

POLR1A polymerase (RNA) I polypeptide A, 194kDa 1.241458 0.0372547

SMC6 structural maintenance of chromosomes 6 2.772324 0.01058738

CUL3 cullin 3 2.512555 0.03000904

CDV3 CDV3 homolog (mouse) 3.247154 0.0416902

SH3 domain binding glutamic acid-rich

SH3BGRL protein like 3.242215 0.02599374

SMYD2 SET and MYND domain containing 2 2.182951 0.03899734

EEF2 eukaryotic translation elongation factor 2 3.218901 0.03839601

IARS2 isoleucyl-tRNA synthetase 2, mitochondrial 2.915579 0.02633645

CAPN7 Calpain 7 3.213705 0.016063 succinate dehydrogenase complex, subunit

SDHA A, flavoprotein (Fp) 3.197073 0.01758965

HAT1 histone acetyltransferase 1 3.188148 0.03486096

SQLE squalene epoxidase 3.159715 0.01084816 chaperonin containing TCP1, subunit 5

CCT5 (epsilon) 2.739476 0.00602847

DBl/ 69437516.1 Supplemental Table 4: Gene Transcripts Upregulated by Lactate in MCF7 Cells that are in Common with Neural Stem Cells

Fold Ttest P

Gene Symbol Gene Description Change value

R F14 ring finger protein 14 3.131844 0.01179033 HDAC2 histone deacetylase 2 1.713956 0.04708192

M-phase phosphoprotein 10 (U3 small

MPHOSPH10 nucleolar ribonucleoprotein) 2.045137 0.0353561 mutS homolog 2, colon cancer, nonpolyposis

MSH2 type 1 (E. coli) 2.98112 0.03627096 SF3B1 splicing factor 3b, subunit 1, 155kDa 3.079506 0.04359828 TCP1 t-complex 1 2.899216 0.02939434 HIBCH 3 -hydroxyisobutyryl-Co A hydrolase 3.065273 0.01688263 guanine nucleotide binding protein (G

GNB1 protein), beta polypeptide 1 3.050983 0.02355176 SP3 Sp3 transcription factor 3.033516 0.00452105

La ribonucleoprotein domain family,

LARP7 member 7 3.023688 0.02499879 family with sequence similarity 98, member

FAM98A A 2.506122 0.01113668 MORF4L2 mortality factor 4 like 2 2.984871 0.03027653 nuclear casein kinase and cyclin-dependent

NUCKS1 kinase substrate 1 2.746242 0.01149953

CCNC cyclin C 2.948678 0.00690543

ENY2 enhancer of yellow 2 homolog (Drosophila) 2.948102 0.00070793

PRP4 pre-mRNA processing factor 4

PRPF4B homolog B (yeast) 2.165609 0.03223181 RAB10 RAB10, member RAS oncogene family 2.675383 0.00826866

SMT3 suppressor of mif two 3 homolog 1

SUMOl (S. cerevisiae) 2.939321 0.01314778 SENP6 SUMOl sentrin specific peptidase 6 2.92259 0.01329545 malic enzyme 1, NADP(+)-dependent,

ME1 cytosolic 2.879955 0.00454168

CRTAP cartilage associated protein 1.943159 0.02923402

USP39 ubiquitin specific peptidase 39 2.866674 0.00731577

LTV1 LTV1 homolog (S. cerevisiae) 2.862159 0.03848354

MTIF2 mitochondrial translational initiation factor 2 1.631234 0.04677842

CCDC99 coiled-coil domain containing 99 2.834983 0.04509615

ZNF644 zinc finger protein 644 2.83475 0.02847176

UDP-GlcNAc:betaGal beta-l,3-N-

B3GNT2 acetylglucosaminyltransferase 2 2.830064 0.02052011 SMC3 structural maintenance of chromosomes 3 2.825491 0.03046467 TBL1XR1 transducin (beta)-like 1 X-Iinked receptor 1 2.821702 0.01803827 COPG coatomer protein complex, subunit gamma 2.406812 0.03959455

DnaJ (Hsp40) homolog, subfamily B,

DNAJB11 member 11 2.813687 0.01128434

BTF3 basic transcription factor 3 2.504564 0.04945883

USP34 ubiquitin specific peptidase 34 2.781149 0.03969944

RAS p21 protein activator (GTPase

RASA1 activating protein) 1 2.760016 0.02594615 EBNA1BP2 EBNA1 binding protein 2 2.743401 0.02486242 coatomer protein complex, subunit beta 2

COPB2 (beta prime) 1.897638 0.00131933

DBl/ 69437516.1 Supplemental Table 4: Gene Transcripts Upregulated by Lactate in MCF7 Cells that are in Common with Neural Stem Cells

Fold Ttest P

Gene Symbol Gene Description Change value

CCAAT/enhancer binding protein (C EBP),

CEBPZ zeta 2.730668 0.04807979

SGOL1 shugoshin-like 1 (S. pombe) 2.730587 0.02367326

SEC63 SEC63 homolog (S. cerevisiae) 2.3961 0.00304391

HMGB2 high-mobility group box 2 1.972844 0.03882638

DYNC1I2 dynein, cytoplasmic 1, intermediate chain 2 1.410334 0.0279939

RWDD1 RWD domain containing 1 2.70643 0.03976333

PSIP1 PC4 and SFRS1 interacting protein 1 2.704173 0.00379656

TRIO triple functional domain (PTPRF interacting) 1.971861 0.04525982

PPIC peptidylprolyl isomerase C (cyclophilin C) 2.684486 0.01273313

ATPase, H+ transporting, lysosomal 42kDa,

ATP6V1C1 VI subunit Cl 2.667986 0.01481745 RARS arginyl-tRNA synthetase 1.592423 0.02013136

DEAD (Asp-Glu-Ala-Asp) box polypeptide

DDX18 18 2.65979 0.04995911

TOPBP1 topoisomerase (DNA) II binding protein 1 2.659609 0.01512887

UNC50 unc-50 homolog (C. elegans) 2.129257 0.03952495 excision repair cross-complementing rodent

ERCC5 repair deficiency, complementation group 5 2.64652 0.03234078

ZNF326 Zinc finger protein 326 2.639598 0.00776776

LAMC1 laminin, gamma 1 (formerly LAMB2) 2.186259 0.01464433

PDLIM7 PDZ and LIM domain 7 (enigma) 1.560624 0.01849702

RFC1 replication factor C (activator 1) 1, 145kDa 2.116992 0.00583182

SF3B5 splicing factor 3 b, subunit 5, lOkDa 2.593595 0.01024026

ANKRD17 ankyrin repeat domain 17 2.592918 0.00227678

ARF4 ADP-ribosylation factor 4 2.58944 0.01239217

TRAF family member-associated NFKB

TANK activator 2.583302 0.02722171

CSNK1A1 casein kinase 1 , alpha 1 2.565332 0.02008984

NCOR1 nuclear receptor co-repressor 1 1.264318 0.04431849 epidermal growth factor receptor pathway

EPS8 substrate 8 2.029185 0.01334663 caspase 2, apoptosis-related cysteine

CASP2 peptidase 2.555936 0.0459927 PNPT1 polyribonucleotide nucleotidyltransferase 1 1.565445 0.03732588 RAB1A RAB1A, member RAS oncogene family 2.373609 0.04191459 proteasome (prosome, macropain) 26S

PSMD14 subunit, non- ATPase, 14 2.533865 0.02390241

NOTCH3 Notch homolog 3 (Drosophila) 2.518418 0.02050312

SRPK2 SFRS protein kinase 2 1.22325 0.01501723

MRPL3 mitochondrial ribosomal protein L3 2.298195 0.03084317

PLK4 polo-like kinase 4 (Drosophila) 2.510571 0.02626713

ARP3 actin-related protein 3 homolog

ACTR3 (yeast) 2.500061 0.02540777

MOB1, Mps One Binder kinase activator¬

MOBKL1A like 1A (yeast) 2.495315 0.01061014 USP3 ubiquitin specific peptidase 3 2.491308 0.03275649 glycerol-3-phosphate dehydrogenase 2

GPD2 (mitochondrial) 2.471884 0.03872717

DBl/ 69437516.1 Supplemental Table 4: Gene Transcripts Upregulated by Lactate in MCF7 Cells that are in Common with Neural Stem Cells

Fold Ttest P

Gene Symbol Gene Description Change value

STK38 serine/threonine kinase 38 1.642924 0.01632112 solute carrier family 39 (zinc transporter),

SLC39A6 member 6 1.22186 0.0061314 synaptotagmin binding, cytoplasmic R A

SYNCRIP interacting protein 1.957398 0.0125552

CLIC4 chloride intracellular channel 4 2.420927 0.04525662

ZNF639 zinc finger protein 639 1.539132 0.03676195

CCND1 Cyclin Dl 1.930024 0.02353764

TAGLN2 transgelin 2 2.407305 0.03670214 nucleophosmin (nucleolar phosphoprotein

NPM1 B23, numatrin) 2.406641 0.01665033

GRN granulin 1.493607 0.03683456

Proteasome (prosome, macropain) 26S

PSMD6 subunit, non-ATPase, 6 2.138274 0.03380946

LIM and senescent cell antigen-like domains

LIMS1 1 1.72779 0.04472927

KIF2C kinesin family member 2C 2.338823 0.02722488 phosphoinositide-3 -kinase, catalytic, alpha

PIK3CA polypeptide 1.728352 0.03384356

AK2 adenylate kinase 2 2.32623 0.04153099

BCAP29 B-cell receptor-associated protein 29 1.927448 0.02335138 polycystic kidney disease 2 (autosomal

PKD2 dominant) 2.312196 0.00272198

PDCD6IP programmed cell death 6 interacting protein 1.970203 0.00643999

PCBP4 poly(rC) binding protein 4 2.297239 0.0480034

IMMT inner membrane protein, mitochondrial 2.291678 0.02551435

Stress-associated endoplasmic reticulum

SERP1 protein 1 1.536698 0.00112698 transforming, acidic coiled-coil containing

TACC3 protein 3 2.268162 0.01045492

MTX1 metaxin 1 2.240865 0.04610751

TBC1 (tre-2/USP6, BUB2, cdcl6) domain

TBC1D1 family, member 1 2.235136 0.00238682

TFB2M transcription factor B2, mitochondrial 2.068018 0.03582113

SCARB2 scavenger receptor class B, member 2 2.225542 0.00468326

KPNA1 karyopherin alpha 1 (importin alpha 5) 2.225491 0.02352899 mitogen-activated protein kinase kinase

MAP4K4 kinase kinase 4 2.068156 0.00788839

PKN2 protein kinase N2 1.81078 0.03572897

USP1 ubiquitin specific peptidase 1 2.204293 0.02425862 succinate-CoA ligase, ADP-forming, beta

SUCLA2 subunit 2.028111 0.02841861

3-hydroxy-3-methylglutaryl-CoA synthase 1

HMGCS1 (soluble) 2.202971 0.04764687

PPIE peptidylprolyl isomerase E (cyclophilin E) 2.202103 0.03374511

ADP-ribosylation factor guanine nucleotide-

ARFGEF1 exchange factor l(brefeldin A-irihibited) 2.200694 0.03552716

STT3, subunit of the

STT3B oligosaccharyltransferase complex, homolog 2.199036 0.03541682

DB1/ 69₄37516.1 Supplemental Table 4: Gene Transcripts Upregulated by Lactate in MCF7 Cells that are in Common with Neural Stem Cells

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Gene Symbol Gene Description Change value

B (S. cerevisiae)

SFRS1 1 splicing factor, arginine/serine-rich 11 2.197102 0.03128218

ZNF281 zinc finger protein 281 2.19509 0.01743985 mutL homolog 1, colon cancer, nonpolyposis

MLH1 type 2 (E. coli) 2.1927 0.00460208

TMEM70 transmembrane protein 70 2.18302 0.01 154643

TTC1 tetratricopeptide repeat domain 1 2.063528 0.04752468

SEC31A SEC31 homolog A (S. cerevisiae) 2.1652 0.02487707 hypoxia inducible factor 1 , alpha subunit

HIF1A (basic helix-loop-helix transcription factor) 1.591415 0.00884964

SEC24B SEC24 family, member B (S. cerevisiae) 2.151645 0.01992121

EIF4E eukaryotic translation initiation factor 4E 2.049544 0.0267098

ACTL6A actin-like 6A 1.640505 0.04155384 solute carrier family 35 (CMP-sialic acid

SLC35A1 transporter), member Al 1.492421 0.03009839

SLBP stem-loop binding protein 1.980568 0.02420595

IK IK cytokine, down-regulator of HLA II 1.365648 0.01056745 protein disulfide isomerase family A,

PDIA6 member 6 1.533451 0.01326546

SMAP1 small ArfGAP 1 2.089852 0.00484321

DTL denticleless homolog (Drosophila) 1.436258 0.00228503

YIPF5 Yipl domain family, member 5 2.076073 0.03670269 asp (abnormal spindle) homolog,

ASPM microcephaly associated (Drosophila) 1.803894 0.04304251

RRM2 ribonucleotide reductase M2 2.012222 0.02429985 protein phosphatase 1 , regulatory (inhibitor)

PPP1R15B subunit 15B 2.067971 0.00766167

HTATSF1 HIV-1 Tat specific factor 1 2.065056 0.04590911

NAV2 neuron navigator 2 2.05691 0.03319842 isocitrate dehydrogenase 1 (NADP+),

IDH1 soluble 2.052557 0.02683413

BAX BCL2-associated X protein 2.048317 0.039567

PMPCB peptidase (mitochondrial processing) beta 2.037316 0.0072201

MRPS2 Mitochondrial ribosomal protein S2 2.036969 0.01324621

MRPL9 mitochondrial ribosomal protein L9 2.03358 0.0281763

TNPOl transportin 1 2.032411 0.03457859

MOCO sulphurase C-terminal domain

MOSC2 containing 2 2.027181 0.00651172

PPP4R2 Protein phosphatase 4, regulatory subunit 2 2.027077 0.02103272

ARP2 actin-related protein 2 homolog

ACTR2 (yeast) 2.013524 0.01953361 leucine zipper-EF-hand containing

LETM1 transmembrane protein 1 1.698753 0.02155205 guanine nucleotide binding protein-like 3

GNL3 (nucleolar) 2.005014 0.01735622

DECPvl 2,4-dienoyl CoA reductase 1 , mitochondrial 2.006511 0.02598747

AQR aquarius homolog (mouse) 1.544351 0.01005732 capping protein (actin filament) muscle Z-

CAPZA1 line, alpha 1 2.003944 0.00987919

DBl/ 69437516.1 Supplemental Table 4: Gene Transcripts Upregulated by Lactate in MCF7 Cells that are in Common with Neural Stem Cells

Fold Ttest P

Gene Symbol Gene Description Change value

FH fumarate hydratase 1.987209 0.01470817

MRPS5 mitochondrial ribosomal protein S5 1.641288 0.02848696 LIMD1 LIM domains containing 1 1.390887 0.01945038 THUMPD3 THUMP domain containing 3 1.798321 0.02891873 nuclear autoantigenic sperm protein (histone-

NASP binding) 1.586624 0.02198518 WDR26 WD repeat domain 26 1.766404 0.04389929 heterogeneous nuclear ribonucleoprotein L-

HNRPLL like 1.965554 0.02133848 WTAP Wilms tumor 1 associated protein 1.777876 0.00868387

LSM3 homolog, U6 small nuclear RNA

LSM3 associated (S. cerevisiae) 1.95834 0.040095

HDAC1 histone deacetylase 1 1.957793 0.03332611

ZMAT3 zinc finger, matrin type 3 1.954859 0.02830097

GYS1 glycogen synthase 1 (muscle) 1.207255 0.0073425

R F2 ring finger protein 2 1.951609 0.00229371

FOXN2 forkhead box N2 1.948693 0.00671655

RAB23 RAB23, member RAS oncogene family 1.52539 0.01869873

SNX5 sorting nexin 5 1.941349 0.00305077

GDI2 GDP dissociation inhibitor 2 1.939501 0.0168794

SPATA5 Spermatogenesis associated 5 1.938449 0.01321604

MRPL37 mitochondrial ribosomal protein L37 1.265484 0.03009753

APEX nuclease (multifunctional DNA repair

APEX1 enzyme) 1 1.937633 0.01208949

CDK8 cyclin-dependent kinase 8 1.937355 0.03136558

NCBP2 nuclear cap binding protein subunit 2, 20kDa 1.937007 0.02064931

HINT1 histidine triad nucleotide binding protein 1 1.210712 0.04891515

ITSN1 intersectin 1 (SH3 domain protein) 1.920858 0.04228789

BLZF1 basic leucine zipper nuclear factor 1 1.920386 0.01207716

Ctr9, Pafl/RNA polymerase II complex

CTR9 component, homolog (S. cerevisiae) 1.911411 0.00146435

SLTM SAFB-like, transcription modulator 1.495363 0.02071 192

KPNA3 karyopherin alpha 3 (importin alpha 4) 1.382818 0.0289694

STX7 syntaxin 7 1.888885 0.02528416

NBR1 neighbor of BRC A 1 gene 1 1.888532 0.01926365

EVI5 ecotropic viral integration site 5 1.883555 0.02040397

RPE ribulose-5-phosphate-3-epimerase 1.72725 0.04901899 proteasome (prosome, macropain) subunit,

PSMB1 beta type, 1 1.877973 0.0332617 CAPN2 calpain 2, (m/II) large subunit 1.868506 0.02067163

N-acylsphingosine amidohydrolase (acid

ASAH1 ceramidase) 1 1.273185 0.03366104 ubiquitin-fold modifier conjugating enzyme

UFC1 1 1.294642 0.04198936 epithelial cell transforming sequence 2

ECT2 oncogene 1.412257 0.00609004

TAF9 RNA polymerase II, TATA box

binding protein (TBP)-associated factor,

TAF9 32kDa 1.586724 0.04658612

DBl/ 69437516.1 Supplemental Table 4: Gene Transcripts Upregulated by Lactate in MCF7 Cells that are in Common with Neural Stem Cells

Fold Ttest P

Gene Symbol Gene Description Change value

GNPDA1 glucosamine-6-phosphate deaminase 1 1.850039 0.01637317 GOLPH3 golgi phosphoprotein 3 (coat-protein) 1.768741 0.03226337 protein-kinase, interferon-inducible double

stranded RNA dependent inhibitor, repressor

PRKRIR of (P58 repressor) 1.836748 0.03060855 proteasome (prosome, macropain) 26S

PSMC1 subunit, ATPase, 1 1.83611 0.03905445 GYG1 glycogenin 1 1.833606 0.0066626 serine threonine kinase 39 (STE20/SPS1

STK39 homolog, yeast) 1.729703 0.04202932

KIAA1524 KIAA1524 1.24618 0.02323518

YAP1 Yes-associated protein 1 1.824953 0.04116296 proteasome (prosome, macropain) subunit,

PSMA7 alpha type, 7 1.814899 0.0228106

NADH dehydrogenase (ubiquinone) 1,

NDUFC1 subcomplex unknown, 1, 6kDa 1.814744 0.00472754 blocked early in transport 1 homolog (S.

BET1 cerevisiae) 1.810406 0.04306222 protein tyrosine phosphatase, non-receptor

PTPN9 type 9 1.806452 0.03400917 roundabout, axon guidance receptor,

ROBOl homolog 1 (Drosophila) 1.802834 0.03733771 PIAS2 protein inhibitor of activated STAT, 2 1.475327 0.02186057 solute carrier family 1 (glutamate/neutral

SLC1A4 amino acid transporter), member 4 1.794159 0.0013034

DnaJ (Hsp40) homolog, subfamily C,

DNAJC13 member 13 1.616418 0.01480203 succinate-CoA ligase, GDP-forming, beta

SUCLG2 subunit 1.786827 0.00924396

SAP30 Sin3A-associated protein, 30kDa 1.783367 0.04714102

SUZ12 suppressor of zeste 12 homolog (Drosophila) 1.781738 0.0427054 acidic (leucine-rich) nuclear phosphoprotein

ANP32A 32 family, member A 1.773795 0.00540646

DDR1 discoidin domain receptor tyrosine kinase 1 1.769628 0.02493444

ZNF213 zinc finger protein 213 1.76888 0.02160061 down-regulator of transcription 1 , TBP-

DR1 binding (negative cofactor 2) 1.767005 0.02631065

PRKD1 protein kinase Dl 1.366096 0.02015636

RYK RYK receptor-like tyrosine kinase 1.751194 0.00185441 eukaryotic translation initiation factor 4

EIF4G1 gamma, 1 1.750254 0.00740522

Methylcrotonoyl-Coenzyme A carboxylase 1

MCCC1 (alpha) 1.746294 0.0228626 CCNB1 cyclin Bl 1.315053 0.02415274 mitogen-activated protein kinase kinase

MAP3K7 kinase 7 1.743976 0.02238046 small nuclear ribonucleoprotein polypeptide

SNRPC C 1.742362 0.04469681 UBA2 ubiquitin-like modifier activating enzyme 2 1.536631 0.03719408

DBl/ 69437516.1 Supplemental Table 4: Gene Transcripts Upregulated by Lactate in MCF7 Cells that are in Common with Neural Stem Cells

Fold Ttest P

Gene Symbol Gene Description Change value

ZZZ3 zinc finger, ZZ-type containing 3 1.36524 0.02901362 solute carrier family 30 (zinc transporter),

SLC30A5 member 5 1.603386 0.01412032

CDC42SE1 CDC42 small effector 1 1.524227 0.02124608 amylo-alpha-1, 6-glucosidase, 4-alpha-

AGL glucanotransferase 1.305308 0.02445334 inhibitor of Bruton agammaglobulinemia

IBTK tyrosine kinase 1.625579 0.01834248

FIGNL1 fidgetin-like 1 1.724436 0.041 13886 budding uninhibited by benzimidazoles 1

BUB1 homolog (yeast) 1.272392 0.01439459

GNPAT glyceronephosphate O-acyltransferase 1.167893 0.02519736

PRP38 pre-mRNA processing factor 38

PRPF38A (yeast) domain containing A 1.267458 0.0372219

ER degradation enhancer, mannosidase

EDEM3 alpha-like 3 1.356732 0.04196012

PHTF2 Putative homeodomain transcription factor 2 1.498429 0.01305125

YTHDF3 YTH domain family, member 3 1.548102 0.02135835

PRKD3 protein kinase D3 1.302343 0.04005699

NIT2 nitrilase family, member 2 1.697659 0.03895012 translocase of outer mitochondrial membrane

TOMM70A 70 homolog A (S. cerevisiae) 1.442531 0.03272251

CENPK centromere protein K 1.364588 0.03575031 protein phosphatase 1 , regulatory (inhibitor)

PPP1R2 subunit 2 1.693178 0.00191476

CPNE3 copine III 1.691682 0.00274705 procollagen-lysine, 2-oxoglutarate 5-

PLOD3 dioxygenase 3 1.342835 0.02428522

C8or03 chromosome 8 open reading frame 33 1.689323 0.0139295

DAP death-associated protein 1.688477 0.00441882

CDC5L CDC5 cell division cycle 5 -like (S. pombe) 1.686596 0.00513394

DnaJ (Hsp40) homolog, subfamily B,

DNAJB6 member 6 1.68511 0.02203927

DnaJ (Hsp40) homolog, subfamily C,

DNAJC10 member 10 1.229817 0.03064105 chaperonin containing TCP1, subunit 3

CCT3 (gamma) 1.663267 0.04685597

UTP18, small subunit (SSU) processome

UTP18 component, homolog (yeast) 1.23789 0.01561913

RAD17 RAD 17 homolog (S. pombe) 1.601375 0.0208996 ribosome binding protein 1 homolog 180kDa

RRBP1 (dog) 1.676273 0.03208152

QARS glutaminyl-tRNA synthetase 1.580939 0.0125861 1

PTPRJ protein tyrosine phosphatase, receptor type, J 1.360438 0.03523859

USP24 ubiquitin specific peptidase 24 1.317279 0.04933808

ELAV (embryonic lethal, abnormal vision,

ELAVL1 Drosophila)-like 1 (Hu antigen R) 1.640597 0.03564955

ACTB actin, beta 1.633494 0.04468234

NCAPH non-SMC condensin I complex, subunit H 1.370164 0.01932908 1/ 69437516.1 Supplemental Table 4: Gene Transcripts Upregulated by Lactate in MCF7 Cells that are in Common with Neural Stem Cells

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Gene Symbol Gene Description Change value

ORMDL1 ORMl-like 1 (S. cerevisiae) 1.54414 0.02275899

UDP-N-acetyl-alpha-D- galactosaminerpolypeptide N- acetylgalactosaminyltransferase 1 (GalNAc-

GALNT1 Tl) 1.626164 0.03763074 TMEM30A transmembrane protein 3 OA 1.62414 0.00774066 OXCT1 3-oxoacid Co A transferase 1 1.261625 0.02520766 LTA4H leukotriene A4 hydrolase 1.386545 0.03548382

DEAD (Asp-Glu-Ala-Asp) box polypeptide

DDX41 41 1.613103 0.01994811 TM9SF2 transmembrane 9 superfamily member 2 1.599129 0.0469163 DLL1 delta-like 1 (Drosophila) 1.343162 0.02388195 MFN1 mitofusin 1 1.251298 0.03838396 large subunit GTPase 1 homolog (S.

LSG1 cerevisiae) 1.30556 0.02208307 RFC5 replication factor C (activator 1) 5, 36.5kDa 1.583884 0.00493414 LAP3 leucine aminopeptidase 3 1.260347 0.04343932 solute carrier family 4, sodium bicarbonate

SLC4A7 cotransporter, member 7 1.200374 0.01216306 GGCX gamma-glutamyl carboxylase 1.38939 0.0460239 carboxyl ester lipase (bile salt-stimulated

CEL lipase) 1.568045 0.03937509

INTS7 integrator complex subunit 7 1.563662 0.04482643

MTMR10 myotubularin related protein 10 1.561932 0.0103955

APAF1 apoptotic peptidase activating factor 1 1.306905 0.03041618

E2F5 E2F transcription factor 5, pl30-binding 1.549601 0.03693464

BTB and CNC homology 1 , basic leucine

BACH1 zipper transcription factor 1 1.234722 0.01598341 protein tyrosine phosphatase, non-receptor

PTPN2 type 2 1.54739 0.02035435 diacylglycerol O-acyltransferase homolog 1

DGAT1 (mouse) 1.54416 0.01906196 CPT1A carnitine palmitoyltransferase 1 A (liver) 1.541995 0.0455955 ZNF35 zinc finger protein 35 1.462328 0.01374461 minichromosome maintenance complex

MCM3 component 3 1.204643 0.02501993

SRR serine racemase 1.451819 0.03543625

PPA2 pyrophosphatase (inorganic) 2 1.533368 0.01586952 suppression of tumorigenicity 13 (colon

ST13 carcinoma) (Hsp70 interacting protein) 1.392146 0.02567641 RGS7 regulator of G-protein signaling 7 1.528987 0.01630161 PCSK7 proprotein convertase subtilisin/kexin type 7 1.52515 0.00584015 WDR77 WD repeat domain 77 1.161034 0.0464362 calcium/calmodulin-dependent serine protein

CASK kinase (MAGUK family) 1.509852 0.02504441 LAS1L LAS 1 -like (S. cerevisiae) 1.523924 0.0047693 inner centromere protein antigens

INCENP 135/155kDa 1.521596 0.00926599 COL11A1 collagen, type XI, alpha 1 1.358775 0.01500244 17 69437516.1 Supplemental Table 4: Gene Transcripts Upregulated by Lactate in MCF7 Cells that are in Common with Neural Stem Cells

Fold Ttest P

Gene Symbol Gene Description Change value

ANGPTL4 Angiopoietin-like 4 1.36763 0.03038604 GUSB glucuronidase, beta 1.483723 0.00747287 MYO10 myosin X 1.361879 0.04208556 MID2 midline 2 1.500591 0.0169234 elongation factor Tu GTP binding domain

EFTUD2 containing 2 1.454941 0.01886939 RNASEH2B ribonuclease H2, subunit B 1.499052 0.02568195

Neural precursor cell expressed,

NEDD1 developmentally down-regulated 1 1.37119 0.0359751 HTRA2 HtrA serine peptidase 2 1.381 117 0.04940812 tankyrase, TRF1 -interacting ankyrin-related

TNKS2 ADP-ribose polymerase 2 1.413046 0.03105238

ITFG1 integrin alpha FG-GAP repeat containing 1 1.266819 0.01601937

CDH2 cadherin 2, type 1, N-cadherin (neuronal) 1.395061 0.04529743

SASH1 SAM and SH3 domain containing 1 1.404986 0.01632024

TYSND1 trypsin domain containing 1 1.470886 0.03841107 phospholipase A2, group VI (cytosolic,

PLA2G6 calcium-independent) 1.465765 0.02742349 solute carrier family 15 (H+/peptide

SLC15A2 transporter), member 2 1.314537 0.01002407

TM7SF3 transmembrane 7 superfamily member 3 1.388536 0.01990459

RBM8A RNA binding motif protein 8A 1.250975 0.00571058 phospholipase Dl, phosphatidylcholine-

PLD1 specific 1.373202 0.04783635

SBF2 SET binding factor 2 1.453314 0.01078788

WEE1 WEE1 homolog (S. pombe) 1.401628 0.01546795

BRD7 bromodomain containing 7 1.448578 0.00933436

TMEM14C transmembrane protein 14C 1.447908 0.01223887

TRIM27 tripartite motif-containing 27 1.447185 0.04931129 family with sequence similarity 50, member

FAM50A A 1.384223 0.02964922

DDHD1 DDHD domain containing 1 1.435652 0.02093535

SEC24C SEC24 family, member C (S. cerevisiae) 1.443774 0.03113679

ATP-binding cassette, sub-family A (ABCl),

ABCA1 member 1 1.366742 0.00856212

EPAS1 endothelial PAS domain protein 1 1.437838 0.02537747

RNASEH2C ribonuclease H2, subunit C 1.436884 0.04326723 nuclear receptor subfamily 1, group H,

NR1H4 member 4 1.43593 0.01391427 nucleolar complex associated 4 homolog (S.

NOC4L cerevisiae) 1.335968 0.0161945

FHL1 four and a half LIM domains 1 1.282345 0.00644461

HSDL2 hydroxysteroid dehydrogenase like 2 1.250353 0.0421 1 176 dihydrolipoamide branched chain

DBT transacylase E2 1.298264 0.03189072 UBE2Z ubiquitin-conjugating enzyme E2Z 1.424388 0.04566522 VAC 14 Vacl4 homolog (S. cerevisiae) 1.422842 0.03352068 vacuolar protein sorting 53 homolog (S.

VPS53 cerevisiae) 1.421566 0.046940931/ 694₃7516.1 Supplemental Table 4: Gene Transcripts Upregulated by Lactate in MCF7 Cells that are in Common with Neural Stem Cells

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Gene Symbol Gene Description Change value

ectonucleoside triphosphate

ENTPD5 diphosphohydrolase 5 1.419164 0.02048402 CKMT2 creatine kinase, mitochondrial 2 (sarcomeric) 1.414046 0.0128032 nudix (nucleoside diphosphate linked moiety

NUDT21 X)-type motif 21 1.249476 0.04665571 epidermal growth factor receptor

(erythroblastic leukemia viral (v-erb-b)

EGFR oncogene homolog, avian) 1.166192 0.04292096 MEIS1 Meis homeobox 1 1.400454 0.04054264 retinol dehydrogenase 11 (all-trans/9-cis/l 1-

RDH11 cis) 1.397657 0.0050891 SNAP23 synaptosomal-associated protein, 23kDa 1.330166 0.03566571 translocase of inner mitochondrial membrane

TIMM44 44 homolog (yeast) 1.394702 0.02292879

ATP -binding cassette, sub-family F

ABCF2 (GCN20), member 2 1.394627 0.03672061 eukaryotic translation initiation factor 2-

EIF2AK3 alpha kinase 3 1.298331 0.04888608

PAK1IP1 PA 1 interacting protein 1 1.26866 0.0392548

BLM Bloom syndrome, RecQ helicase-like 1.392962 0.02331052

BAG2 BCL2-associated athanogene 2 1.390864 0.00399346

SYTL4 synaptotagmin-like 4 1.387118 0.02970297

PNKD Paroxysmal nonkinesigenic dyskinesia 1.304131 0.02809504

USP38 ubiquitin specific peptidase 38 1.37522 0.04727816 inositol polyphosphate- 5 -phosphatase,

INPP5D 145kDa 1.374524 0.00364048 caspase 6, apoptosis-related cysteine

CASP6 peptidase 1.372269 0.04203738 ADAM28 ADAM metallopeptidase domain 28 1.277873 0.00355689

NGFI-A binding protein 2 (EGR1 binding

NAB2 protein 2) 1.364006 0.02567161 NPC1 Niemann-Pick disease, type CI 1.362315 0.04477366

ADAMDEC1 ADAM-like, decysin 1 1.362129 0.03679769

PELI1 pellino homolog 1 (Drosophila) 1.35374 0.01691951

DAP3 death associated protein 3 1.271808 0.02339598

LIG1 ligase I, DNA, ATP-dependent 1.268785 0.01252088

CDCA8 Cell division cycle associated 8 1.340746 0.04499828

ROD1 regulator of differentiation 1 (S.

ROD1 pombe) 1.200754 0.0474292 E2F8 E2F transcription factor 8 1.232086 0.00048585 cyclin-dependent kinase inhibitor 2C (pi 8,

CDKN2C inhibits CD 4) 1.33462 0.04260088

I PPL1 inositol polyphosphate phosphatase-like 1 1.329887 0.00979076

TSPAN12 tetraspanin 12 1.211375 0.02651059

NSUN4 NOP2/Sun domain family, member 4 1.327342 0.03660922

HTATIP2 HIV-1 Tat interactive protein 2, 30kDa 1.258927 0.00915241 serpin peptidase inhibitor, clade H (heat

shock protein 47), member 1, (collagen

SERPINHl binding protein 1) 1.32396 0.01919945

DBl/ 69437516.1 Supplemental Table 4: Gene Transcripts Upregulated by Lactate in MCF7 Cells that are in Common with Neural Stem Cells

Fold Ttest P

Gene Symbol Gene Description Change value

ABHD5 abhydrolase domain containing 5 1.259035 0.00596344

MDFIC MyoD family inhibitor domain containing 1.242969 0.03261241

SMO smoothened omolog (Drosophila) 1.320865 0.03439192

C14orfl47 chromosome 14 open reading frame 147 1.319192 0.03875552

R F26 ring finger protein 26 1.242143 0.04297931

C3orf58 chromosome 3 open reading frame 58 1.259091 0.04608467

A2M alpha-2-macroglobulin 1.293429 0.00961782

FBXW2 F-box and WD repeat domain containing 2 1.284946 0.03658627

SFRS16 splicing factor, arginine/serine-rich 16 1.289527 0.00918842 eukaryotic translation elongation factor 1

EEF1D delta (guanine nucleotide exchange protein) 1.299174 0.02232024

DIDOl death inducer-obliterator 1 1.28637 0.02217596

WDR46 WD repeat domain 46 1.179087 0.01295145 cleavage stimulation factor, 3' pre-RNA,

CSTF2 subunit 2, 64kDa 1.283423 0.02479593

TPMT thiopurine S -methyl transferase 1.282727 0.0166767

ATPase, H+ transporting, lysosomal

ATP6V1H 50/57kDa, VI subunit H 1.211331 0.026815 origin recognition complex, subunit 1-like

ORC1L (yeast) 1.273124 0.03331651 protein tyrosine phosphatase, receptor type,

PTPRA A 1.24583 0.00032856 platelet-activating factor acetylhydrolase lb,

PAFAH1B3 catalytic subunit 3 (29kDa) 1.268768 0.02361777

SFXN1 sideroflexin 1 1.262718 0.02940824

SEC23A Sec23 homolog A (S. cerevisiae) 1.166758 0.0064721 v-crk sarcoma virus CT10 oncogene

CRKL homolog (avian)-like 1.22546 0.02004339

IMP (inosine 5'-monophosphate)

IMPDH2 dehydrogenase 2 1.186305 0.02984448

SIN3 homolog B, transcription regulator

SIN3B (yeast) 1.247232 0.0053172

INHBB inhibin, beta B 1.238504 0.00822597 translocase of inner mitochondrial membrane

TIMM8A 8 homolog A (yeast) 1.154276 0.01892605

THOC4 THO complex 4 1.216787 0.0403008

ACINI apoptotic chromatin condensation inducer 1 1.201026 0.02887224

Supplemental Table 5: Gene Transcripts Upregulated by Ketones in MCF7 Cells that are in Common with Hematopoietic Stem Cells

Gene Fold Ttest

Symbol Gene Description Change P value

CHMP7 CHMP family, member 7 3.295925 0.04618667

INADL InaD-like (Drosophila) 2.899368 0.00507621

ERRFIl ERBB receptor feedback inhibitor 1 2.848611 0.03785734

MED 12 mediator complex subunit 12 1.963442 0.04534554

DDHD2 DDHD domain containing 2 2.735836 0.04539782 1/ 69437516 1 Supplemental Table 5: Gene Transcripts Up regulated by Ketones in MCF7 Cells that are in Common with Hematopoietic Stem Cells

Gene Fold Ttest Symbol Gene Description Change P value

nudix (nucleoside diphosphate linked moiety

NUDT9 X)-type motif 9 2.735101 0.00850058

DIAPH1 diaphanous homolog 1 (Drosophila) 2.685718 0.03000495

FUR Fl l receptor 1.585065 0.04318684

ADAR adenosine deaminase, RNA-specific 1.970478 0.02323278

LGALS8 lectin, galactoside-binding, soluble, 8 1.607202 0.03947108

POLR1B polymerase (RNA) I polypeptide B, 128kDa 1.430873 0.01550162 excision repair cross-complementing rodent

ERCC5 repair deficiency, complementation group 5 1.324623 0.03590136

IFITM3 #N/A 2.435717 0.04163527

MCRS1 microspherule protein 1 2.42666 0.04946973

ATPase, Na+/K+ transporting, alpha 1

ATP1A1 polypeptide 1.582011 0.01059971

EDF1 #N/A 2.424154 0.04204104 solute carrier family 20 (phosphate transporter),

SLC20A1 member 1 1.821633 0.01516049

INVS inversin 2.402863 0.01659962

NICNl nicolin l 2.388529 0.00908688

WDFY2 WD repeat and FYVE domain containing 2 2.369515 0.01867335

GLUL glutamate-ammonia ligase 2.013353 0.01359148

TP53BP1 tumor protein p53 binding protein 1 1.653193 0.03890936

TSPAN31 tetraspanin 31 1.998064 0.04403488

TTC4 tetratricopeptide repeat domain 4 2.305393 0.01134933

ELOVL family member 6, elongation of long

chain fatty acids (FENl/Elo2, SUR4/Elo3-like,

ELOVL6 yeast) 2.298864 0.02905437

OSBPL1A oxysterol binding protein-like 1 A 2.28078 0.03304009 solute carrier family 4, sodium bicarbonate

SLC4A7 cotransporter, member 7 2.276701 0.00738148

HINT2 histidine triad nucleotide binding protein 2 2.272342 0.02016666

PDE8A phosphodiesterase 8A 1.960537 0.01873747

PRUNE prune homolog (Drosophila) 2.261951 0.04105039

CRTAP cartilage associated protein 1.194501 0.01415943

ATP-binding cassette, sub-family G (WHITE),

ABCG2 member 2 2.258303 0.02678408

COQ9 coenzyme Q9 homolog (S. cerevisiae) 1.921458 0.01957612

DCTN1 dynacti l (pi 50, glued homolog, Drosophila) 2.247297 0.0361356

RDHl 1 retinol dehydrogenase 11 (all-trans/9-cis/l 1 -cis) 1.594865 0.03426753 cyclin-dependent kinase inhibitor 1A (p21,

CDKN1A Cipl) 2.238879 0.01566499

LSG1 large subunit GTPase 1 homolog (S. cerevisiae) 2.107797 0.03808136

IFIH1 interferon induced with helicase C domain 1 1.824823 0.04845467

SRPK2 SFRS protein kinase 2 1.531659 0.03108475

GTF2IRD2 GTF2I repeat domain containing 2 1.614706 0.0087574

HDLBP high density lipoprotein binding protein 1.370587 0.02901277 phosphoinositide-3 -kinase, regulatory subunit 1

PIK3R1 (alpha) 1.724967 0.04257376

SEC14L2 SEC14-like 2 (S. cerevisiae) 2.197791 0.02157167

HTRA2 HtrA serine peptidase 2 1.842614 0.04774984

DBl/ 69437516.1 Supplemental Table 5: Gene Transcripts Upregulated by Ketones in MCF7 Cells that are in Common with Hematopoietic Stem Cells

Gene Fold Ttest Symbol Gene Description Change P value

FBXW11 F-box and WD repeat domain containing 11 2.088765 0.00313297 ANKRD17 ankyrin repeat domain 17 1.43046 0.04827993 TCEA2 transcription elongation factor A (SII), 2 2.187952 0.04357233 FBXL3 F-box and leucine-rich repeat protein 3 2.176911 0.01974647

O-linked N-acetylglucosamine (GlcNAc)

transferase (UDP-N- acetylglucosamine:polypeptide-N-

OGT acetylglucosaminyl transferase) 1.728718 0.04340233

MYCBP2 MYC binding protein 2 2.168534 0.02526474

IRF7 interferon regulatory factor 7 2.163552 0.01010416

NAV2 neuron navigator 2 1.835983 0.04928384

MACF1 microtubule-actin crosslinking factor 1 2.062381 0.03102047 ashl (absent, small, or homeotic)-like

ASH1L (Drosophila) 1.331452 0.03902654 RBBP6 retinoblastoma binding protein 6 1.479665 0.04940251 chaperonin containing TCP1, subunit 3

CCT3 (gamma) 2.143663 0.03791006 UBAP2L ubiquitin associated protein 2-like 1.205878 0.04256504 NDRG2 NDRG family member 2 1.640909 0.03953699 METTL3 methyltransferase like 3 1.487554 0.03923316

TATA box binding protein (TBP)-associated

TAFIA factor, RNA polymerase I, A, 48kDa 2.123803 0.01221043

LATS, large tumor suppressor, homolog 2

LATS2 (Drosophila) 2.119657 0.02938295 ST7 suppression of tumorigenicity 7 1.530312 0.02388241 poly(A)-specific ribonuclease (deadenylation

PARN nuclease) 2.111073 0.03680447

PLK2 polo-like kinase 2 (Drosophila) 1.89847 0.02392197

SPG20 spastic paraplegia 20 (Troyer syndrome) 2.103392 0.00306415

MPDU1 mannose-P-dolichol utilization defect 1 2.102917 0.01760447

PHF23 #N/A 2.10236 0.00738597

POM121 POM121 membrane glycoprotein (rat) 1.25332 0.04289457

HSPC159 galectin-related protein 1.276374 0.0439434

DnaJ (Hsp40) homolog, subfamily B, member

DNAJB6 6 2.086418 0.03741646 ZNF638 zinc finger protein 638 2.082689 0.00361861 phosphatidylinositol transfer protein,

PITPNM1 membrane-associated 1 2.08004 0.02403844

DNA cross-link repair 1 A (PS02 homolog, S.

DCLRE1A cerevisiae) 2.070302 0.00827517 low density lipoprotein receptor-related protein

LRP10 10 2.065981 0.04553922

ULK1 unc-51-like kinase 1 (C. elegans) 1.376606 0.04913687

TNRC6A trinucleotide repeat containing 6A 1.452047 0.02369483

PPAP2A phosphatidic acid phosphatase type 2A 1.582666 0.00144035

TTC17 tetratricopeptide repeat domain 17 1.672722 0.02732361

RREBl ras responsive element binding protein 1 1.462738 0.0215814 polymerase (RNA) III (DNA directed)

POLR3A polypeptide A, 155kDa 2.037793 0.04734161

DB1/ 694375I6.I Supplemental Table 5: Gene Transcripts Upregulated by Ketones in MCF7 Cells that are in Common with Hematopoietic Stem Cells

Gene Fold Ttest

Symbol Gene Description Change P value

DDIT3 DNA-damage-inducible transcript 3 2.035672 0.01260509

DDX51 DEAD (Asp-Glu-Ala-Asp) box polypeptide 51 1.548135 0.04765583

FASN fatty acid synthase 1.948427 0.02462526

C2or£28 chromosome 2 open reading frame 28 1.474813 0.01733917 mitogen-activated protein kinase kinase kinase

MAP4K4 kinase 4 1.712186 0.04245277

PEX19 peroxisomal biogenesis factor 19 2.008181 0.00973182

BET1L #N/A 2.00183 0.04957609 diacylglycerol O-acyltransferase homolog 1

DGAT1 (mouse) 1.749071 0.03456439

TK2 thymidine kinase 2, mitochondrial 1.60101 0.04195181

SMYD2 SET and MYND domain containing 2 1.552349 0.04941773

TRAFD1 TRAF-type zinc finger domain containing 1 1.941885 0.02871056 v-erb-b2 erythroblastic leukemia viral oncogene

ERJBB3 homolog 3 (avian) 1.981818 0.04875523 ectonucleotide

ENPP1 pyrophosphatase/phosphodiesterase 1 1.981336 0.01844171

STX12 syntaxin 12 1.977998 0.03106077

SHROOM3 shroom family member 3 1.977414 0.01628976

PGM2 Phosphoglucomutase 2 1.781686 0.02399861

ZMYM4 zinc finger, MYM-type 4 1.432183 0.03154925

TSC22D1 TSC22 domain family, member 1 1.152544 0.04055428

LDB1 LIM domain binding 1 1.768377 0.04418318

TMEM70 transmembrane protein 70 1.950205 0.02384912

BCL2L11 BCL2-like 11 (apoptosis facilitator) 1.943373 0.01340632

RAS p21 protein activator (GTPase activating

RASA1 protein) 1 1.943062 0.01887466

LIMA1 LIM domain and actin binding 1 1.941669 0.04567907

EIF2C2 eukaryotic translation initiation factor 2C, 2 1.737381 0.02796271

PRP39 pre-mRNA processing factor 39

PRPF39 homolog (S. cerevisiae) 1.263236 0.03313913

BAT3 HLA-B associated transcript 3 1.612256 0.02485149 glycerol-3 -phosphate dehydrogenase 2

GPD2 (mitochondrial) 1.923915 0.02166602

IL11RA interleukin 11 receptor, alpha 1.919985 0.01904984

WNK1 WNK lysine deficient protein kinase 1 1.589806 0.03200462

ASXL1 additional sex combs like 1 (Drosophila) 1.470256 0.00998521

BMP2K BMP2 inducible kinase 1.386192 0.04872796

PIAS3 protein inhibitor of activated STAT, 3 1.912841 0.01839942 histidyl-tRNA synthetase 2, mitochondrial

HARS2 (putative) 1.715719 0.03591061 transducin-like enhancer of split 1 (E(s l)

TLE1 homolog, Drosophila) 1.9081 18 0.04074464 amyloid beta (A4) precursor protein-binding,

APBB2 family B, member 2 1.90255 0.03919277

GSTA4 glutathione S-transferase alpha 4 1.753107 0.00541283

MYBBP1A MYB binding protein (PI 60) la 1.897963 0.01696392

PHF12 #N/A 1.896855 0.04395523

SCAMPI secretory carrier membrane protein 1 1.57467 0.02157253

DB l/ 69437516.1 Supplemental Table 5: Gene Transcripts Upregulated by Ketones in MCF7 Cells that are in Common with Hematopoietic Stem Cells

Gene Fold Ttest Symbol Gene Description Change P value

RPL22 ribosomal protein L22 0.00202954 VLDLR very low density lipoprotein receptor 0.02591145 RTTN rotatin 0.04473924 REPS1 RALBP1 associated Eps domain containing 1 0.03344135

ATP-binding cassette, sub-family G (WHITE),

ABCG1 member 1 0.03561249 fasciculation and elongation protein zeta 2

FEZ2 (zygin II) 0.01625731 solute carrier family 19 (folate transporter),

SLC19A1 member 1 0.01485065

MFN1 mitofusin 1 0.0499737

BMP7 #N/A 0.04358522

SH3RF1 SH3 domain containing ring finger 1 0.00683851

ACVR2A activin A receptor, type IIA 0.04361939

SWI/SNF related, matrix associated, actin

dependent regulator of chromatin, subfamily a,

SMARCA2 member 2 0.01914396

ITGB4 integrin, beta 4 0.04837165

MTMR1 myotubularin related protein 1 0.01841331 potassium large conductance calcium-activated

KCNMA1 channel, subfamily M, alpha member 1 0.02490189

ELL2 elongation factor, RNA polymerase II, 2 0.02073358

MAPK12 mitogen-activated protein kinase 12 0.02403095

SEC23A Sec23 homolog A (S. cerevisiae) 0.02654777

EPC1 enhancer of polycomb homolog 1 (Drosophila) 0.03620974

SSBP4 single stranded DNA binding protein 4 0.0091075

ZNF692 zinc finger protein 692 0.04823366

FOXP1 forkhead box PI 0.01077085

Smg-5 homolog, nonsense mediated mRNA

SMG5 decay factor (C. elegans) 0.01248203 ASNS asparagine synthetase (glutamine-hydrolyzing) 0.04490557 minichromosome maintenance complex

MCM3AP component 3 associated protein 0.01036449

NUMA1 nuclear mitotic apparatus protein 1 0.02466567

NELF nasal embryonic LHRH factor 0.04955878

RPP14 ribonuclease P/MRP 14kDa subunit 0.04069763

PDK1 pyruvate dehydrogenase kinase, isozyme 1 0.03042126

TPP2 tripeptidyl peptidase II 0.02199587 cytoplasmic polyadenylation element binding

CPEB2 protein 2 0.00139721 ARIH2 ariadne homolog 2 (Drosophila) 0.04036547 erythrocyte membrane protein band 4.1

EPB41 (elliptocytosis l, RH-linked) 0.02384749

ITSN1 intersectin 1 (SH3 domain protein) 0.0462667

LAPTM4B lysosomal protein transmembrane 4 beta 0.01663365

SMAD6 SMAD family member 6 0.04895342

CREM cAMP responsive element modulator 0.01481585

SERTAD1 #N/A 0.03107296

MRPS25 Mitochondrial ribosomal protein S25 0.01791241 1/ 69437516.1 Supplemental Table 5: Gene Transcripts Upregulated by Ketones in MCF7 Cells that are in Common with Hematopoietic Stem Cells

Gene Fold Ttest

Symbol Gene Description Change P value

metal response element binding transcription

MTF2 factor 2 1.431461 0.04435086

SHKBP1 SH3KBP1 binding protein 1 1.789197 0.01337287

PPIL2 peptidylprolyl isomerase (cyclophilin)-like 2 1.619019 0.03839263 adaptor-related protein complex 1 , beta 1

AP1B1 subunit 1.779553 0.01993621

C9orf72 chromosome 9 open reading frame 72 1.779325 0.00116813

WD repeat domain, phosphoinositide

WIPI2 interacting 2 1.777875 0.04845168

DGCR2 DiGeorge syndrome critical region gene 2 1.777194 0.03677183

ELL elongation factor RNA polymerase II 1.775647 0.02696673

TNIP1 TNFAIP3 interacting protein 1 1.362235 0.02962173

LASS2 LAG1 homolog, ceramide synthase 2 1.383183 0.01736726

MAP2K3 mitogen-activated protein kinase kinase 3 1.252382 0.01292775

UBL4A #N/A 1.766604 0.01994057

FOXK2 forkhead box K2 1.483924 0.0323877 nuclear factor of kappa light polypeptide gene

NFKB1 enhancer in B-cells 1 1.466917 0.00255794

ATF3 activating transcription factor 3 1.756661 0.0451451

CEP350 centrosomal protein 350kDa 1.351128 0.03670049

HDDC2 HD domain containing 2 1.153537 0.00641685 sphingomyelin phosphodiesterase 2, neutral

SMPD2 membrane (neutral sphingomyelinase) 1.505414 0.04020793

IARS2 isoleucyl-tRNA synthetase 2, mitochondrial 1.642147 0.03956772

GAB1 GRB2-associated binding protein 1 1.746467 0.03029872

ERF #N/A 1.74482 0.02510774

RYK RYK receptor-like tyrosine kinase 1.461366 0.03625633

STK11IP serine/threonine kinase 11 interacting protein 1.736757 0.02103678

BCL2L13 BCL2-like 13 (apoptosis facilitator) 1.429059 0.02860466

ZBTB2 zinc finger and BTB domain containing 2 1.733558 0.02724021

RAB3IP RAB3A interacting protein (rabin3) 1.73291 0.03062512

GALT galactose- 1 -phosphate uridylyltransferase 1.397966 0.00247261

SELENBP1 selenium binding protein 1 1.548317 0.01943454

Rho guanine nucleotide exchange factor (GEF)

ARHGEF3 3 1.729836 0.04145086 myeloid/lymphoid or mixed-lineage leukemia

(trithorax homolog, Drosophila); translocated

MLLT10 to, 10 1.546189 0.01475505 ariadne homolog, ubiquitin-conjugating enzyme

ARIH1 E2 binding protein, 1 (Drosophila) 1.446394 0.0394967

IRF6 interferon regulatory factor 6 1.713118 0.0205667

CREG1 cellular repressor of ElA-stimulated genes 1 1.310534 0.02867724 mitogen-activated protein kinase kinase kinase

MAP4K3 kinase 3 1.710348 0.01794311

ZFR zinc finger RNA binding protein 1.656317 0.01174294

LysM, putative peptidoglycan-binding, domain

LYSMD2 containing 2 1.589339 0.02093268

LPIN2 lipin 2 1.708429 0.00705372

TFB2M transcription factor B2, mitochondrial 1.414276 0.00766602

>B1/ 69437516.1 Supplemental Table 5: Gene Transcripts Upregulated by Ketones in MCF7 Cells that are in Common with Hematopoietic Stem Cells

Gene Fold Ttest Symbol Gene Description Change P value

FXYD domain containing ion transport

FXYD5 regulator 5 1.701181 0.0201854 FNBP4 formin binding protein 4 1.349354 0.00845931

BTB and CNC homology 1 , basic leucine

BACH1 zipper transcription factor 1 1.696301 0.02582705 transmembrane emp24 protein transport domain

TMED4 containing 4 1.694517 0.0165239 retinol saturase (all-trans-retinol 13,14-

RETSAT reductase) 1.692359 0.0411033

GAS 8 growth arrest-specific 8 1.55427 0.0138367

IDH3A isocitrate dehydrogenase 3 (NAD+) alpha 1.683264 0.04905133

TES testis derived transcript (3 LIM domains) 1.542686 0.0424636

EZH1 enhancer of zeste homolog 1 (Drosophila) 1.569122 0.03681327

PXN paxillin 1.283966 0.04880114

TWSG1 Twisted gastrulation homolog 1 (Drosophila) 1.590384 0.03366619

PPP1R15A #N/A 1.666918 0.00530079

PDCD2 programmed cell death 2 1.664955 0.02292029

MTMR10 myotubularin related protein 10 1.594912 0.01191

GPR133 G protein-coupled receptor 133 1.349679 0.02919616

CASP3 caspase 3, apoptosis-related cysteine peptidase 1.275471 0.00672259 succinate-CoA ligase, GDP-forming, beta

SUCLG2 subunit 1.61146 0.01434601

PITX2 #N/A 1.38095 0.03603224

RNASEH1 ribonuclease HI 1.22204 0.02031113

PELI1 pellino homolog 1 (Drosophila) 1.47698 0.03398163

EFNA1 #N/A 1.641752 0.02231982

JUP junction plakoglobin 1.639367 0.03601004 phosphoinositide-3-kinase, regulatory subunit 2

PIK3R2 (beta) 1.6247 0.04549777

USP38 ubiquitin specific peptidase 38 1.328488 0.03761775

TBRG4 #N/A 1.40939 0.02950791

N4BP1 NEDD4 binding protein 1 1.180702 0.04692864

ZFP28 zinc finger protein 28 homolog (mouse) 1.270796 0.03986652

PDCD6IP programmed cell death 6 interacting protein 1.341445 0.02712429

TSN translin 1.399509 0.03659249

ZMYM6 zinc finger, MYM-type 6 1.607937 0.03222668 tissue factor pathway inhibitor (lipoprotein-

TFPI associated coagulation inhibitor) 1.170572 0.03900407

RIT1 Ras-like without CAAX 1 1.493381 0.00705308

ZFP30 #N/A 1.606079 0.04811928

JUN jun oncogene 1.60477 0.01920584

E2F5 E2F transcription factor 5, pl30-binding 1.574504 0.04111575

SMYD1 #N/A 1.602613 0.03160765

GFPT2 glutamine-fructose-6-phosphate transaminase 2 1.601761 0.00786173 solute carrier family 1 (glutamate/neutral amino

SLC1A4 acid transporter), member 4 1.601111 0.01714116 MAPK8 mitogen-activated protein kinase 8 1.352867 0.03733872 LM02 #N/A 1.585683 0.01178633 IKBKE inhibitor of kappa light polypeptide gene 1.585318 0.02560331

DBl/ 69437516.1 Supplemental Table 5: Gene Transcripts Upregulated by Ketones in MCF7 Cells that are in Common with Hematopoietic Stem Cells

Gene Fold Ttest

Symbol Gene Description Change P value

enhancer in B-cells, kinase epsilon

polycystic kidney disease 2 (autosomal

PKD2 dominant) 1.355906 0.03251514

RASA3 RAS p21 protein activator 3 1.580655 0.03063955

ZNF703 zinc finger protein 703 1.553516 0.0157481

SCMH1 sex comb on midleg homolog 1 (Drosophila) 1.374893 0.04735748

DAB2IP DAB2 interacting protein 1.325257 0.04430944

MFHAS1 #N/A 1.429933 0.04621658 ubiquitin specific peptidase 7 (herpes virus-

USP7 associated) 1.2173 0.03971564 solute carrier family 12

(sodium/potassium/chloride transporters),

SLC12A2 member 2 1.379717 0.01203849

TEC Tec protein tyrosine kinase 1.561419 0.04835099 lymphotoxin beta receptor (TNFR superfamily,

LTBR member 3) 1.56131 0.01734089

CD83 CD83 molecule 1.393225 0.03750887

BAIAP2 BAI1 -associated protein 2 1.558511 0.02805553 mutS homolog 2, colon cancer, nonpolyposis

MSH2 type 1 (E. coli) 1.301052 0.00303927

ALDH7A1 aldehyde dehydrogenase 7 family, member Al 1.521211 0.04933379

COX 17 cytochrome c oxidase assembly

COX17 homolog (S. cerevisiae) 1.548985 0.00063577 proteasome (prosome, macropain) 26 S subunit,

PSMD12 non-ATPase, 12 1.54839 0.03297181

DYNC1I1 dynein, cytoplasmic 1, intermediate chain 1 1.547255 0.0015712

COL4A1 collagen, type IV, alpha 1 1.340948 0.04402007 protein tyrosine phosphatase, non-receptor type

PTP 18 18 (brain-derived) 1.5449 0.04522658

PPFIBP2 #N/A 1.513922 0.01840277

RBPMS RNA binding protein with multiple splicing 1.422673 0.04119182

ANKRD28 ankyrin repeat domain 28 1.522866 0.0295649

C10orf58 #N/A 1.392475 0.0313261

WDR13 WD repeat domain 13 1.53985 0.02618777

ATP-binding cassette, sub-family A (ABC1),

ABCA1 member 1 1.53626 0.0201419 dolichyl-phosphate mannosyltransferase

DPM2 polypeptide 2, regulatory subunit 1.42053 0.00599389

PHKG2 phosphorylase kinase, gamma 2 (testis) 1.532241 0.03755378 myeloid/lymphoid or mixed-lineage leukemia

(trithorax homolog, Drosophila); translocated

MLLT3 to, 3 1.336207 0.0340955

GALC #N/A 1.337734 0.04874618

FLT3LG fms-related tyrosine kinase 3 ligand 1.524077 0.01175394

ZNF436 zinc finger protein 436 1.523707 0.04067693

HDAC5 histone deacetylase 5 1.313934 0.0481495

IFNGR1 interferon gamma receptor 1 1.485695 0.03541863

SRRM1 serine/arginine repetitive matrix 1 1.449417 0.01719139

RABEP1 rabaptin, RAB GTPase binding effector protein 1.202797 0.0453199

DBl/ 69437516.1 Supplemental Table 5: Gene Transcripts Upregulated by Ketones in MCF7 Cells that are in Common with Hematopoietic Stem Cells

Gene Fold Ttest

Symbol Gene Description Change P value

1

BMP1 bone morphogenetic protein 1 1.32758 0.03343608

MCOLN2 mucolipin 2 1.51452 0.04997968

EFNB2 ephrin-B2 1.511313 0.02811974 interleukin 16 (lymphocyte chemoattractant

IL16 factor) 1.499957 3.09E-06

FAM91A1 family with sequence similarity 91, member Al 1.407477 0.01878871

WDR78 WD repeat domain 78 1.499613 0.03715928

TRAF family member-associated NFKB

TANK activator 1.24674 0.02488358

KIFAP3 kinesin-associated protein 3 1.458765 0.04901628

LARS Leucyl-tRNA synthetase 1.46382 0.02711871

PGCP plasma glutamate carboxypeptidase 1.485871 0.00774448

VAMP5 #N/A 1.48482 0.02867714

LDHB lactate dehydrogenase B 1.484571 0.01769543 cytochrome P450, family 51, subfamily A,

CYP51A1 polypeptide 1 1.483035 0.00605888

NCKAPl NCK-associated protein 1 1.372116 0.02620886

TCF15 transcription factor 15 (basic helix-loop-helix) 1.474894 0.00719009

KRT7 keratin 7 1.345142 0.04343201

FBX09 F-box protein 9 1.276761 0.02422462 solute carrier family 4, anion exchanger,

SLC4A3 member 3 1.472698 0.01015349

SYTL4 synaptotagmin-like 4 1.427768 0.0322787

ZNF213 zinc finger protein 213 1.463007 0.01143018 nuclear factor I/X (CCAAT-binding

NFIX transcription factor) 1.458648 0.02610177

ZNF622 zinc finger protein 622 1.305364 0.03391459

GAA glucosidase, alpha; acid 1.390145 0.02416388

UBC #N/A 1.39239 0.04488279

NKIRAS1 NFKB inhibitor interacting Ras-like 1 1.434868 0.04111426

IL4R interleukin 4 receptor 1.367682 0.0474 193

PYCRL pyrroline-5-carboxylate reductase-like 1.383376 0.02332003 protein tyrosine phosphatase, non-receptor type

PTP 12 12 1.407633 0.04343223

CD34 CD34 molecule 1.406256 0.02143454

IFRD1 interferon-related developmental regulator 1 1.223621 0.0461768 transcription elongation factor B (SIII),

TCEB3 polypeptide 3 (1 lOkDa, elongin A) 1.403204 0.03240308

EPRS glutamyl-prolyl-tRNA synthetase 1.308599 0.02361163

ATP5D #N/A 1.386046 0.03800337

AEBP2 AE binding protein 2 1.362569 0.03985048

ZFX #N/A 1.254057 0.02842691

BCL3 B-cell CLL/lymphoma 3 1.338873 0.03515185

MRPL3 mitochondrial ribosomal protein L3 1.321518 0.01629641 mitogen-activated protein kinase kinase kinase

MAP3K11 11 1.262091 0.02976909 eukaryotic translation initiation factor 4E

EIF4EBP1 binding protein 1 1.242901 0.033296661/ 69437516.1 Supplemental Table 6. Gene Transcripts Upregulated by Lactate in MCF7 Cells that are in Common with a Multiple Myeloma (MM) Signature.

Only in Fold Ttest

Lactate Gene Description Change P value

glycine cleavage system protein H

GCSH (aminomethyl carrier) 6.024608 0.04401522

ASF1 anti-silencing function 1 homolog A (S.

ASF1A cerevisiae) 4.469944 0.01353041 signal transducing adaptor molecule (SH3

STAM2 domain and ITAM motif) 2 4.170061 0.00948584

MINA MYC induced nuclear antigen 4.035887 0.00750673

DBF4 DBF4 homolog (S. cerevisiae) 3.845044 0.01450426 chaperonin containing TCP1, subunit 5

CCT5 (epsilon) 2.739476 0.00602847

DMXL1 Dmx-like 1 3.07451 1 0.00708549

KRIT1 KRITl, ankyrin repeat containing 2.533715 0.00341833

EBNA1BP2 EBNA1 binding protein 2 2.743401 0.02486242

DDX18 DEAD (Asp-Glu- Ala-Asp) box polypeptide 18 2.65979 0.04995911

DnaJ (Hsp40) homolog, subfamily B, member

DNAJB14 14 2.625377 0.00031245

Split hand/foot malformation (ectrodactyly)

SHFM1 type 1 2.411671 0.02417581

C7orf30 chromosome 7 open reading frame 30 2.375592 0.00732418 protein phosphatase 1, regulatory (inhibitor)

PPP1R12A subunit 12A 2.277063 0.04329455 protein kinase, DNA-activated, catalytic

PRKDC polypeptide 1.496476 0.04042323

IK IK cytokine, down-regulator of HLA II 1.365648 0.01056745

LRRC40 leucine rich repeat containing 40 2.063667 0.0216401

SLC25A36 solute carrier family 25, member 36 2.031104 0.01642812 nuclear autoantigenic sperm protein (histone-

NASP binding) 1.586624 0.02198518 telomeric repeat binding factor (NIMA-

TERF1 interacting) 1 1.863569 0.01246509

UPF3 regulator of nonsense transcripts

UPF3A homolog A (yeast) 1.23028 0.0287505 intraflagellar transport 57 homolog

IFT57 (Chlamydomonas) 1.410484 0.02169174 intraflagellar transport 74 homolog

IFT74 (Chlamydomonas) 1.369324 0.01094548

LEMD3 LEM domain containing 3 1.44673 0.04092375 fibroblast growth factor (acidic) intracellular

FIBP binding protein 1.599584 0.00865392

LAP3 leucine aminopeptidase 3 1.260347 0.04343932

DHX29 DEAH (Asp-Glu-Ala-His) box polypeptide 29 1.4701 13 0.01019979

ABHD3 abhydrolase domain containing 3 1.547037 0.04585433

GEMIN5 gem (nuclear organelle) associated protein 5 1.439594 0.0397608 elongation factor Tu GTP binding domain

EFTUD2 containing 2 1.454941 0.01886939

C15orf41 chromosome 15 open reading frame 41 1.442137 0.04387507

ERCC1 excision repair cross-complementing rodent 1.265089 0.04242011

DBl/ 69437516.1 Supplemental Table 6. Gene Transcripts Upregulated by Lactate in MCF7 Cells that are in Common with a Multiple Myeloma (MM) Signature.

Only in Fold Ttest

Lactate Gene Description Change P value

repair deficiency, complementation group 1

(includes overlapping antisense sequence)

PAK1IP1 PAK1 interacting protein 1 1.26866 0.0392548

SNX19 Sorting nexin 19 1.382253 0.03833771

ILF3 interleukin enhancer binding factor 3, 90kDa 1.243423 0.02255549 translocase of inner mitochondrial membrane

TIMM50 50 homolog (S. cerevisiae) 1.300325 4.55E-05

TRIB1 tribbles homolog 1 (Drosophila) 1.184163 0.02736849

Supplemental Table 7: Gene Transcripts Upregulated by Lactate in MCF7 Cells that are in Common with a Hepatocellular Carcinoma (HCC) Signature

Only in Fold Ttest P Lactate Gene Description Change value

CD2AP CD2-associated protein 2.509456 0.04171078

RPS3A ribosomal protein S3A 4.603982 0.03886604

CCT6A chaperonin containing TCP1, subunit 6A (zeta 1) 2.226682 0.02645749

CENPF centromere protein F, 350/400ka (mitosin) 3.299657 0.01890505

ZNF 138 zinc finger protein 138 3.162613 0.04255118

CCT5 chaperonin containing TCP1, subunit 5 (epsilon) 2.739476 0.00602847

HDAC2 histone deacetylase 2 1.713956 0.04708192

ANLN anillin, actin binding protein 3.097471 0.03519748

HMGB2 high-mobility group box 2 1.972844 0.03882638

RWDD1 RWD domain containing 1 2.70643 0.03976333

ACTR3 ARP3 actin-related protein 3 homolog (yeast) 2.500061 0.02540777 nucleophosmin (nucleolar phosphoprotein B23,

NPM1 numatrin) 2.406641 0.01665033

EEF1E1 eukaryotic translation elongation factor 1 epsilon 1 2.394143 0.01844291

RPL9 ribosomal protein L9 1.678778 0.02683837

USP1 ubiquitin specific peptidase 1 2.204293 0.02425862 hypoxia inducible factor 1, alpha subunit (basic helix-

HIF 1 A loop-helix transcription factor) 1.591415 0.00884964 tyrosine 3-monooxygenase/tryptophan 5-

YWHAQ monooxygenase activation protein, theta polypeptide 2.122941 0.02980982

PCNA proliferating cell nuclear antigen 1.306526 0.02897492

RPL 12 ribosomal protein L 12 1.645702 0.03148393

NCBP2 nuclear cap binding protein subunit 2, 20kDa 1.937007 0.02064931

RPE ribulose-5-phosphate-3-epimerase 1.72725 0.04901899

ECT2 epithelial cell transforming sequence 2 oncogene 1.412257 0.00609004

UBA2 ubiquitin-like modifier activating enzyme 2 1.536631 0.03719408

NFE2L3 nuclear factor (erythroid-derived 2)-like 3 1.738235 0.01922635

KNTC1 kinetochore associated 1 1.573628 0.03209189

LAMB 1 laminin, beta 1 1.484995 0.00653142

SLC34A1 solute carrier family 34 (sodium phosphate), member 1 1.357953 0.01540008

KLF5 Kruppel-like factor 5 (intestinal) 1.349817 0.03913202

ROD1 ROD1 regulator of differentiation 1 (S. pombe) 1.200754 0.0474292 serpin peptidase inhibitor, clade H (heat shock protein

SERPINH1 47), member 1, (collagen binding protein 1) 1.32396 0.01919945

DBl/ 69437516.1 Supplemental Table 7: Gene Transcripts Upregulated by Lactate in MCF7 Cells that are in Common with a Hepatocellular Carcinoma (HCC) Signature

Only in Fold Ttest P Lactate Gene Description Change value

UDP-GlcNAc:betaGal beta-l,3-N- B3GNT5 acetylglucosaminyltransferase 5 1.200695 0.01960692

DB1/ 694375I6.1

Claims

1. A method for identifying a mammalian cell as neoplastic, the method comprising detecting in a test mammalian cell (e.g. breast cancer cell) a level of gene expression pattern or activity, wherein the level of gene expression pattern or activity is induced by a set of at least one high-energy metabolite (e.g., ketones or lactate or acetoacetate or oxaloacetate or citrate or a- ketoglutarate or glutamine); and identifying the test mammalian cell as neoplastic when a difference between the level of gene expression pattern or activity in the test mammalian cell and a corresponding level of gene expression pattern or activity in a control mammalian cell is detected.

2. A method for selecting a therapeutic strategy for treating a cancer patient, the method comprising identifying a therapeutic agent which inhibits metabolite-induced gene expression pattern or activity of a set of genes, the method comprising (a) subjecting an in vitro cell culture of cancer cells to treatment with a set of at least one or more metabolites to induce gene expression pattern or activity of a set of genes, wherein the set of genes is selected from at least one table from the group consisting of Tables 1-7; (b) thereafter treating the cell culture with the therapeutic agent; and (c) comparing the level of gene expression pattern or activity caused by the set of at least one or more metabolites, wherein a corresponding gene expression pattern or activity in a control cancer cell culture not treated with the set of the set at least one or more metabolites, wherein a difference in the level of gene expression pattern or active is indicative of the ability of the therapeutic agent to treat cancer in the cancer patient.

3. A method for evaluating gene expression in cancer cells, the method comprising treating an in vitro culture of cancer cells with a set of at least one high-energy metabolite (such as glutamine, acetoacetate, lactate or 3-hydroxybutyrate); and assessing changes in gene expression resulting from the treatment with said set of at least one metabolite; wherein said method comprises generating labeled polynucleotide molecules corresponding to cancer genes having changes in expression resulting from the treatment with said set of at least one metabolite; and wherein said method further comprises applying said labeled molecules to a microarray having immobilized human genes to evaluate gene expression.

4. A method for identifying a set of at least one cancer associated gene, expression of which is induced by a set of at least one or more metabolites, the method comprising: (a) subjecting an in vitro cancer cell culture to treatment with the set of at least one or more metabolites; (b)

DBl/ 69437516.1 thereafter assessing the level of gene expression in the cancer cell culture; and (c) comparing the level of gene expression in the cancer cell culture with the level of gene expression a control cell culture, wherein the control cell had not been treated with the at least one or more metabolites; whereby a difference between the level of gene expression in the in vitro cancer cell culture and the level of gene expression in the control cell culture is an indication that the gene expression pattern of the set of at least one cancer associated gene is induced by the set of at least one or more metabolites; wherein said method further comprises generating labeled polynucleotide molecules corresponding to the at least one cancer associated gene having changes in expression resulting from the treatment with said set of at least one high-energy metabolite, and wherein said method further comprises applying said labeled molecules to a microrray having immobilized human genes to identify the at least one cancer associated gene.

5. A method for predicting a clinical outcome in a cancer patient, comprising (a) subjecting a first in vitro culture of cancer cells derived from a sample obtained from a cancer patient to treatment with a set of at least one or more metabolites; and (b) assessing a level of gene expression pattern in the first in vitro culture of cancer cells; and (c) comparing the level of gene expression pattern of the first in vitro cancer cell culture with a corresponding level of gene expression pattern in a second in vitro cancer cell culture (control sample) also derived from a sample obtained from the cancer patient, whereby a difference between the level of the gene expression pattern in the first in vitro cancer cell culture and the level of gene expression pattern in the second in vitro cancer cell culture is indicative of the clinical outcome (e.g., high risk of cancer recurrence, or high risk of cancer metastasis, and decreased overall survival).

6. The method of claim 5, wherein the clinical outcome predicts prognosis for survival.

7. The method of claim 5, wherein the clinical outcome is a poor clinical outcome (e.g., shorter survival or shorter overall survival).

8. The method of claim 5, wherein the clinical outcome is selected from the group consisting of recurrence of cancer, increased survival of cancer, shorter survival of cancer, and cancer progression in the cancer patient.

9. The method of claim 5, wherein the clinical outcome is selected from the group consisting of decreased overall survival of cancer and/or increased likelihood of cancer progression in the cancer patient.

10. A method of stratifying a subject or a group of subjects having a cancer for a clinical trial, the method comprising: (a) treating an in vitro culture of cancer cells derived from a biological

DBl/ 69437516.1 sample obtained from the subject or each member of the group of subjects having the cancer with a set of at least one or more metabolites (such as 3-hydroxybutyrate, lactate, glutamine and acetoacetate); (b) assessing changes in gene expression induced by said set of at least one or more metabolites; (c) comparing the level of gene expression in the in vitro culture of cancer cells with a level of gene expression in a control cancer cell culture; and (d) stratifying the subject or the group of subjects for the clinical trial on the basis of a difference between the level of gene expression in the in vitro culture of cancer cells and the level of gene expression in the control cancer cell culture.

1 1. A method for culturing stem cells, including mesenchymal stem cells, embryonic stem cells, including human embryonic stem cells, said method comprising growing said stem cells in a culture medium in the presence of at least one or more metabolites (e.g., acetoacetate, 3- hydroxybutyrate, lactate, glutamine).

12. The method of claim 11, further comprising isolating stem cells from the culture medium.

13. A method for discovering a biological marker (biomarker) of a cancer whose growth is modulated by mitochondrial oxidative metabolism, the method comprising:

(a) contacting a set of at least one or more metabolites (e.g., 3-hydroxybutyrate or lactate or acetoacetate or oxaloacetate or citrate or a-ketoglutarate or glutamine or combinations thereof) to a first sample of a cancer cell line, a test cancer cell line;

(b) assessing a level of gene expression pattern in the test cancer cell line; and (c) comparing the level of gene expression pattern of the test cancer cell line with a level of gene expression pattern in a second sample of the cancer cell line, a control cancer cell line, whereby a difference between the level of the gene expression pattern in the test cancer cell line and the level of gene expression pattern in the control cancer cell line is a biomarker of mitochondrial oxidative metabolism in the cancer represented by the cancer cell. 14. A biomarker discovered according to the method of claim 13.

1 . A method for predicting a clinical outcome in a cancer patient, comprising:

(a) subjecting a first sample of cancer cell line corresponding to the same type of cancer in the cancer patient to treatment with a set of at least one or more metabolites;

(b) assessing a level of gene expression pattern in the first sample of cancer cell line; and

DB l/ 69437516.1 (c) comparing the level of gene expression pattern of the first sample cancer cell line with a level of gene expression pattern in a second sample of the cancer cell line not treated with the at least one or more metabolites, whereby a difference between the level of the gene expression pattern in the first sample of cancer cell line and the level of gene expression pattern in the second sample of the cancer cell line is indicative of the clinical outcome (e.g., high risk of cancer recurrence and/or high risk of cancer metastasis and/or decreased overall survival).

16. A method for selecting a therapeutic strategy for treating a cancer patient, the method comprising identifying a therapeutic agent which prevents or inhibits metabolite-induced gene expression pattern or activity in a sample of cancer cell line corresponding to the same type of cancer in the cancer patient, the method comprising (a) subjecting a first sample of cancer cell line and a second sample of the cancer cell line to treatment with a set of at least one or more metabolites to induce gene expression pattern or activity of a set of genes in the first and second samples of the cancer cell line; (b) thereafter treating the first sample of the cancer cell line with a test therapeutic agent; and (c) comparing the level of gene expression pattern or activity caused by the set of at least one or more metabolites in the first sample of cancer cell line with the level of gene expression pattern or activity in the second sample of the cancer cell line, wherein a difference in the level of gene expression pattern or active is indicative of the ability of the test therapeutic agent to treat cancer in the cancer patient.

DBl 69437516.1