1932

Abstract

Metabolic and epigenetic reprogramming are characteristics of cancer cells that, in many cases, are linked. Oncogenic signaling, diet, and tumor microenvironment each influence the availability of metabolites that are substrates or inhibitors of epigenetic enzymes. Reciprocally, altered expression or activity of chromatin-modifying enzymes can exert direct and indirect effects on cellular metabolism. In this article, we discuss the bidirectional relationship between epigenetics and metabolism in cancer. First, we focus on epigenetic control of metabolism, highlighting evidence that alterations in histone modifications, chromatin remodeling, or the enhancer landscape can drive metabolic features that support growth and proliferation. We then discuss metabolic regulation of chromatin-modifying enzymes and roles in tumor growth and progression. Throughout, we highlight proposed therapeutic and dietary interventions that leverage metabolic-epigenetic cross talk and have the potential to improve cancer therapy.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-cancerbio-070820-035832
2021-03-04
2024-03-29
Loading full text...

Full text loading...

/deliver/fulltext/cancerbio/5/1/annurev-cancerbio-070820-035832.html?itemId=/content/journals/10.1146/annurev-cancerbio-070820-035832&mimeType=html&fmt=ahah

Literature Cited

  1. Affronti HC, Long MD, Rosario SR, Gillard BM, Karasik E et al. 2017. Dietary folate levels alter the kinetics and molecular mechanism of prostate cancer recurrence in the CWR22 model. Oncotarget 8:61103758–74
    [Google Scholar]
  2. Agathocleous M, Meacham CE, Burgess RJ, Piskounova E, Zhao Z et al. 2017. Ascorbate regulates haematopoietic stem cell function and leukaemogenesis. Nature 549:7673476–81
    [Google Scholar]
  3. Alam H, Tang M, Maitituoheti M, Dhar SS, Kumar M et al. 2020. KMT2D deficiency impairs super-enhancers to confer a glycolytic vulnerability in lung cancer. Cancer Cell 37:4599–617.e7
    [Google Scholar]
  4. Atlante S, Visintin A, Marini E, Savoia M, Dianzani C et al. 2018. α-ketoglutarate dehydrogenase inhibition counteracts breast cancer-associated lung metastasis. Cell Death Dis 9:7756
    [Google Scholar]
  5. Attar N, Kurdistani SK. 2017. Exploitation of EP300 and CREBBP lysine acetyltransferases by cancer. Cold Spring Harb. Perspect. Med. 7:3a026534
    [Google Scholar]
  6. Avila MA, García-Trevijano ER, Lu SC, Corrales FJ, Mato JM 2004. Methylthioadenosine. Int. J. Biochem. Cell Biol. 36:112125–30
    [Google Scholar]
  7. Berwick DC, Hers I, Heesom KJ, Kelly Moule S, Tavaré JM 2002. The identification of ATP-citrate lyase as a protein kinase B (Akt) substrate in primary adipocytes. J. Biol. Chem. 277:3733895–900
    [Google Scholar]
  8. Białopiotrowicz E, Noyszewska-Kania M, Kachamakova-Trojanowska N, Łoboda A, Cybulska M et al. 2020. Serine biosynthesis pathway supports MYC–miR-494-EZH2 feed-forward circuit necessary to maintain metabolic and epigenetic reprogramming of Burkitt lymphoma cells. Cancers 12:3580
    [Google Scholar]
  9. Bian Y, Li W, Kremer DM, Sajjakulnukit P, Li S et al. 2020. Cancer SLC43A2 alters T cell methionine metabolism and histone methylation. Nature 585:782427782
    [Google Scholar]
  10. Bistulfi G, Foster BA, Karasik E, Gillard B, Miecznikowski J et al. 2011. Dietary folate deficiency blocks prostate cancer progression in the tramp model. Cancer Prev. Res. 4:111825–34
    [Google Scholar]
  11. Bose S, Allen AE, Locasale JW 2020. The molecular link from diet to cancer cell metabolism. Mol. Cell 78:1034–44
    [Google Scholar]
  12. Bradner JE, Hnisz D, Young RA 2017. Transcriptional addiction in cancer. Cell 168:4629–43
    [Google Scholar]
  13. Bulusu V, Tumanov S, Michalopoulou E, van den Broek NJ, MacKay G et al. 2017. Acetate recapturing by nuclear acetyl-CoA synthetase 2 prevents loss of histone acetylation during oxygen and serum limitation. Cell Rep 18:3647–58
    [Google Scholar]
  14. Camacho-Vanegas O, Camacho SC, Till J, Miranda-Lorenzo I, Terzo E et al. 2012. Primate genome gain and loss: a bone dysplasia, muscular dystrophy, and bone cancer syndrome resulting from mutated retroviral-derived MTAP transcripts. Am. J. Hum. Genet. 90:4614–27
    [Google Scholar]
  15. Campbell SL, Wellen KE. 2018. Metabolic signaling to the nucleus in cancer. Mol. Cell 71:3398–408
    [Google Scholar]
  16. Carrer A, Trefely S, Zhao S, Campbell SL, Norgard RJ et al. 2019. Acetyl-CoA metabolism supports multistep pancreatic tumorigenesis. Cancer Discov 9:3416–35
    [Google Scholar]
  17. Casciello F, Windloch K, Gannon F, Lee JS 2015. Functional role of G9a histone methyltransferase in cancer. Front. Immunol. 6:487
    [Google Scholar]
  18. Cimmino L, Dolgalev I, Wang Y, Yoshimi A, Martin GH et al. 2017. Restoration of TET2 function blocks aberrant self-renewal and leukemia progression. Cell 170:61079–95.e20
    [Google Scholar]
  19. Comerford SA, Huang Z, Du X, Wang Y, Cai L et al. 2014. Acetate dependence of tumors. Cell 159:71591–602
    [Google Scholar]
  20. Comet I, Riising EM, Leblanc B, Helin K 2016. Maintaining cell identity: PRC2-mediated regulation of transcription and cancer. Nat. Rev. Cancer 16:12803–10
    [Google Scholar]
  21. Creighton CJ, Morgan M, Gunaratne PH, Wheeler DA, Gibbs RA et al. 2013. Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature 499:745643–49
    [Google Scholar]
  22. Dang L, White DW, Gross S, Bennett BD, Bittinger MA et al. 2009. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 462:7274739–44
    [Google Scholar]
  23. Deblois G, Madani Tonekaboni SA, Grillo G, Martinez C, Kao YI et al. 2020. Epigenetic switch–induced viral mimicry evasion in chemotherapy resistant breast cancer. Cancer Discov 10:91312–29
    [Google Scholar]
  24. Ding J, Li T, Wang X, Zhao E, Choi JH et al. 2013. The histone H3 methyltransferase G9A epigenetically activates the serine-glycine synthesis pathway to sustain cancer cell survival and proliferation. Cell Metab 18:6896–907
    [Google Scholar]
  25. Dixon SJ, Stockwell BR. 2019. The hallmarks of ferroptosis. Annu. Rev. Cancer Biol. 3:35–54
    [Google Scholar]
  26. Donohoe DR, Collins LB, Wali A, Bigler R, Sun W, Bultman SJ 2012. The Warburg effect dictates the mechanism of butyrate-mediated histone acetylation and cell proliferation. Mol. Cell 48:4612–26
    [Google Scholar]
  27. Donohoe DR, Holley D, Collins LB, Montgomery SA, Whitmore AC et al. 2014. A gnotobiotic mouse model demonstrates that dietary fiber protects against colorectal tumorigenesis in a microbiota- and butyrate-dependent manner. Cancer Discov 4:121387–97
    [Google Scholar]
  28. Eckert MA, Coscia F, Chryplewicz A, Chang JW, Hernandez KM et al. 2019. Proteomics reveals NNMT as a master metabolic regulator of cancer-associated fibroblasts. Nature 569:7758723–28
    [Google Scholar]
  29. Emadi A, Jun SA, Tsukamoto T, Fathi AT, Minden MD, Dang CV 2014. Inhibition of glutaminase selectively suppresses the growth of primary acute myeloid leukemia cells with IDH mutations. Exp. Hematol. 42:4247–51
    [Google Scholar]
  30. Etchegaray JP, Zhong L, Li C, Henriques T, Ablondi E et al. 2019. The histone deacetylase SIRT6 restrains transcription elongation via promoter-proximal pausing. Mol. Cell 75:4683–99.e7
    [Google Scholar]
  31. Favier J, Amar L, Gimenez-Roqueplo AP 2015. Paraganglioma and phaeochromocytoma: from genetics to personalized medicine. Nat. Rev. Endocrinol. 11:2101–11
    [Google Scholar]
  32. Fedoriw A, Rajapurkar SR, O'Brien S, Gerhart SV, Mitchell LH et al. 2019. Anti-tumor activity of the type I PRMT inhibitor, GSK3368715, synergizes with PRMT5 inhibition through MTAP loss. Cancer Cell 36:1100–14.e25
    [Google Scholar]
  33. Flavahan WA, Gaskell E, Bernstein BE 2017. Epigenetic plasticity and the hallmarks of cancer. Science 357:6348eaal2380
    [Google Scholar]
  34. Galdieri L, Gatla H, Vancurova I, Vancura A 2016. Oncogenic activities of IDH1/2 mutations: from epigenetics to cellular signaling. J. Biol. Chem. 291:4825154–66
    [Google Scholar]
  35. Galdieri L, Vancura A. 2012. Acetyl-CoA carboxylase regulates global histone acetylation. J. Biol. Chem. 287:2823865–76
    [Google Scholar]
  36. Gao G, Zhang L, Villarreal OD, He W, Su D et al. 2019a. PRMT1 loss sensitizes cells to PRMT5 inhibition. Nucleic Acids Res 47:105038–48
    [Google Scholar]
  37. Gao X, Sanderson SM, Dai Z, Reid MA, Cooper DE et al. 2019b. Dietary methionine influences therapy in mouse cancer models and alters human metabolism. Nature 572:7769397–401
    [Google Scholar]
  38. Gimple RC, Kidwell RL, Kim LJY, Sun T, Gromovsky AD et al. 2019. Glioma stem cell-specific superenhancer promotes polyunsaturated fatty-acid synthesis to support EGFR signaling. Cancer Discov 9:91248–67
    [Google Scholar]
  39. Golub D, Iyengar N, Dogra S, Wong T, Bready D et al. 2019. Mutant isocitrate dehydrogenase inhibitors as targeted cancer therapeutics. Front. Oncol. 9:417
    [Google Scholar]
  40. González A, Hall MN, Lin SC, Hardie DG 2020. AMPK and TOR: the yin and yang of cellular nutrient sensing and growth control. Cell Metab 31:3472–92
    [Google Scholar]
  41. Gu Z, Liu Y, Cai F, Patrick M, Zmajkovic J et al. 2019. Loss of EZH2 reprograms BCAA metabolism to drive leukemic transformation. Cancer Discov 9:91228–47
    [Google Scholar]
  42. Guy PS, Cohen P, Hardie DG 1980. Rat mammary gland ATP-citrate lyase is phosphorylated by cyclic AMP-dependent protein kinase. FEBS Lett 109:2205–8
    [Google Scholar]
  43. Han M, Jia L, Lv W, Wang L, Cui W 2019. Epigenetic enzyme mutations: role in tumorigenesis and molecular inhibitors. Front. Oncol. 9:194
    [Google Scholar]
  44. Hanahan D, Weinberg RA. 2011. Hallmarks of cancer: the next generation. Cell 144:5646–74
    [Google Scholar]
  45. Hansen LJ, Sun R, Yang R, Singh SX, Chen LH et al. 2019. MTAP loss promotes stemness in glioblastoma and confers unique susceptibility to purine starvation. Cancer Res 79:133383–94
    [Google Scholar]
  46. Hatzivassiliou G, Zhao F, Bauer DE, Andreadis C, Shaw AN et al. 2005. ATP citrate lyase inhibition can suppress tumor cell growth. Cancer Cell 8:4311–21
    [Google Scholar]
  47. Haws SA, Yu D, Ye C, Wille CK, Nguyen LC et al. 2020. Methyl-metabolite depletion elicits adaptive responses to support heterochromatin stability and epigenetic persistence. Mol. Cell 78:2210–23.e8
    [Google Scholar]
  48. Helming KC, Wang X, Roberts CWM 2014. Vulnerabilities of mutant SWI/SNF complexes in cancer. Cancer Cell 26:3309–17
    [Google Scholar]
  49. Hu CY, Mohtat D, Yu Y, Ko YA, Shenoy N et al. 2014. Kidney cancer is characterized by aberrant methylation of tissue-specific enhancers that are prognostic for overall survival. Clin. Cancer Res. 20:164349–60
    [Google Scholar]
  50. Huang CK, Chang PH, Kuo WH, Chen CL, Jeng YM et al. 2017. Adipocytes promote malignant growth of breast tumours with monocarboxylate transporter 2 expression via β-hydroxybutyrate. Nat. Commun. 8:14706
    [Google Scholar]
  51. Intlekofer AM, DeMatteo RG, Venneti S, Finley LWS, Lu C et al. 2015. Hypoxia induces production of L-2-hydroxyglutarate. Cell Metab 22:2304–11
    [Google Scholar]
  52. Intlekofer AM, Wang B, Liu H, Shah H, Carmona-Fontaine C et al. 2017. l-2-Hydroxyglutarate production arises from noncanonical enzyme function at acidic pH. Nat. Chem. Biol. 13:5494–500
    [Google Scholar]
  53. Islam MS, Leissing TM, Chowdhury R, Hopkinson RJ, Schofield CJ 2018. 2-Oxoglutarate-dependent oxygenases. Annu. Rev. Biochem. 87:585–620
    [Google Scholar]
  54. Jeusset L, McManus K. 2019. Developing targeted therapies that exploit aberrant histone ubiquitination in cancer. Cells 8:2165
    [Google Scholar]
  55. Jiang Y, Hu T, Wang T, Shi X, Kitano A et al. 2019. AMP-activated protein kinase links acetyl-CoA homeostasis to BRD4 recruitment in acute myeloid leukemia. Blood 134:242183–94
    [Google Scholar]
  56. Kadariya Y, Yin B, Tang B, Shinton SA, Quinlivan EP et al. 2009. Mice heterozygous for germ-line mutations in methylthioadenosine phosphorylase (MTAP) die prematurely of T-cell lymphoma. Cancer Res 69:145961–69
    [Google Scholar]
  57. Kanarek N, Petrova B, Sabatini DM 2020. Dietary modifications for enhanced cancer therapy. Nature 5789:7800507–17
    [Google Scholar]
  58. Kim Y-I. 2005. Nutritional epigenetics: impact of folate deficiency on DNA methylation and colon cancer susceptibility. J. Nutr. 135:112703–9
    [Google Scholar]
  59. Kim Y-I, Salomon RN, Graeme-Cook F, Choi SW, Smith DE et al. 1996. Dietary folate protects against the development of macroscopic colonic neoplasia in a dose responsive manner in rats. Gut 39:5732–40
    [Google Scholar]
  60. Kohli RM, Zhang Y. 2013. TET enzymes, TDG and the dynamics of DNA demethylation. Nature 502:7472472–79
    [Google Scholar]
  61. Kottakis F, Nicolay BN, Roumane A, Karnik R, Gu H et al. 2016. LKB1 loss links serine metabolism to DNA methylation and tumorigenesis. Nature 539:7629390–95
    [Google Scholar]
  62. Koutsioumpa M, Hatziapostolou M, Polytarchou C, Tolosa EJ, Almada LL et al. 2019. Lysine methyltransferase 2D regulates pancreatic carcinogenesis through metabolic reprogramming. Gut 68:71271–86
    [Google Scholar]
  63. Krautkramer KA, Kreznar JH, Romano KA, Vivas EI, Barrett-Wilt GA et al. 2016. Diet-microbiota interactions mediate global epigenetic programming in multiple host tissues. Mol. Cell 64:5982–92
    [Google Scholar]
  64. Kryukov GV, Wilson FH, Ruth JR, Paulk J, Tsherniak A et al. 2016. MTAP deletion confers enhanced dependency on the PRMT5 arginine methyltransferase in cancer cells. Science 351:62781214–18
    [Google Scholar]
  65. Kugel S, Sebastián C, Fitamant J, Ross KN, Saha SK et al. 2016. SIRT6 suppresses pancreatic cancer through control of Lin28b. Cell 165:61401–15
    [Google Scholar]
  66. Labbé DP, Zadra G, Yang M, Reyes JM, Lin CY et al. 2019. High-fat diet fuels prostate cancer progression by rewiring the metabolome and amplifying the MYC program. Nat. Commun. 10:4358
    [Google Scholar]
  67. Lee JV, Carrer A, Shah S, Snyder NW, Wei S et al. 2014. Akt-dependent metabolic reprogramming regulates tumor cell histone acetylation. Cell Metab 20:2306–19
    [Google Scholar]
  68. Letouzé E, Martinelli C, Loriot C, Burnichon N, Abermil N et al. 2013. SDH mutations establish a hypermethylator phenotype in paraganglioma. Cancer Cell 23:6739–52
    [Google Scholar]
  69. Li X, Egervari G, Wang Y, Berger SL, Lu Z 2018. Regulation of chromatin and gene expression by metabolic enzymes and metabolites. Nat. Rev. Mol. Cell Biol. 19:9563–78
    [Google Scholar]
  70. Li X, Yu W, Qian X, Xia Y, Zheng Y et al. 2017. Nucleus-translocated ACSS2 promotes gene transcription for lysosomal biogenesis and autophagy. Mol. Cell 66:5684–97.e9
    [Google Scholar]
  71. Lin Z, Yang H, Tan C, Li J, Liu Z et al. 2013. USP10 antagonizes c-Myc transcriptional activation through SIRT6 stabilization to suppress tumor formation. Cell Rep 5:61639–49
    [Google Scholar]
  72. Liu X, Olszewski K, Zhang Y, Lim EW, Shi J et al. 2020. Cystine transporter regulation of pentose phosphate pathway dependency and disulfide stress exposes a targetable metabolic vulnerability in cancer. Nat. Cell Biol. 22:4476–86
    [Google Scholar]
  73. Losman JA, Kaelin WG. 2013. What a difference a hydroxyl makes: Mutant IDH, (R)-2-hydroxyglutarate, and cancer. Genes Dev 27:8836–52
    [Google Scholar]
  74. Lu M, Zhu WW, Wang X, Tang JJ, Zhang KL et al. 2019. ACOT12-dependent alteration of acetyl-CoA drives hepatocellular carcinoma metastasis by epigenetic induction of epithelial-mesenchymal transition. Cell Metab 29:4886–900.e5
    [Google Scholar]
  75. Lucena-Cacace A, Otero-Albiol D, Jimenez-García MP, Muñoz-Galvan S, Carnero A 2018. NAMPT is a potent oncogene in colon cancer progression that modulates cancer stem cell properties and resistance to therapy through Sirt1 and PARP. Clin. Cancer Res. 24:51202–15
    [Google Scholar]
  76. Manning BD, Toker A. 2017. AKT/PKB signaling: navigating the network. Cell 169:3381–405
    [Google Scholar]
  77. Marjon K, Cameron MJ, Quang P, Clasquin MF, Mandley E et al. 2016. MTAP deletions in cancer create vulnerability to targeting of the MAT2A/PRMT5/RIOK1 axis. Cell Rep 15:3574–87
    [Google Scholar]
  78. Martinez Calejman C, Trefely S, Entwisle SW, Luciano A, Jung SM et al. 2020. mTORC2-AKT signaling to ATP-citrate lyase drives brown adipogenesis and de novo lipogenesis. Nat. Commun. 11:575
    [Google Scholar]
  79. Mashimo T, Pichumani K, Vemireddy V, Hatanpaa KJ, Singh DK et al. 2014. Acetate is a bioenergetic substrate for human glioblastoma and brain metastases. Cell 159:71603–14
    [Google Scholar]
  80. Mavrakis KJ, McDonald ER, Schlabach MR, Billy E, Hoffman GR et al. 2016. Disordered methionine metabolism in MTAP/CDKN2A-deleted cancers leads to dependence on PRMT5. Science 351:62781208–13
    [Google Scholar]
  81. May JL, Kouri FM, Hurley LA, Liu J, Tommasini-Ghelfi S et al. 2019. IDH3α regulates one-carbon metabolism in glioblastoma. Sci. Adv. 5:1eaat0456
    [Google Scholar]
  82. McBrayer SK, Mayers JR, DiNatale GJ, Shi DD, Khanal J et al. 2018. Transaminase inhibition by 2-hydroxyglutarate impairs glutamate biosynthesis and redox homeostasis in glioma. Cell 175:1101–16.e25
    [Google Scholar]
  83. Michealraj KA, Kumar SA, Kim LJY, Cavalli FMG, Przelicki D et al. 2020. Metabolic regulation of the epigenome drives lethal infantile ependymoma. Cell 181:61329–45.e24
    [Google Scholar]
  84. Mingay M, Chaturvedi A, Bilenky M, Cao Q, Jackson L et al. 2018. Vitamin C-induced epigenomic remodelling in IDH1 mutant acute myeloid leukaemia. Leukemia 32:11–20
    [Google Scholar]
  85. Morin A, Goncalves J, Moog S, Castro-Vega LJ, Job S et al. 2020. TET-mediated hypermethylation primes SDH-deficient cells for HIF2α-driven mesenchymal transition. Cell Rep 30:134551–66.e7
    [Google Scholar]
  86. Morris JP, Yashinskie JJ, Koche R, Chandwani R, Tian S et al. 2019. α-Ketoglutarate links p53 to cell fate during tumour suppression. Nature 573:7775595–99
    [Google Scholar]
  87. Mosammaparast N, Shi Y. 2010. Reversal of histone methylation: biochemical and molecular mechanisms of histone demethylases. Annu. Rev. Biochem. 79:155–79
    [Google Scholar]
  88. Mustafi S, Camarena V, Volmar CH, Huff TC, Sant DW et al. 2018. Vitamin C sensitizes melanoma to BET inhibitors. Cancer Res 78:2572–83
    [Google Scholar]
  89. Nguyen VTM, Barozzi I, Faronato M, Lombardo Y, Steel JH et al. 2015. Differential epigenetic reprogramming in response to specific endocrine therapies promotes cholesterol biosynthesis and cellular invasion. Nat. Commun. 6:10044
    [Google Scholar]
  90. Ogiwara H, Takahashi K, Sasaki M, Kuroda T, Yoshida H et al. 2019. Targeting the vulnerability of glutathione metabolism in ARID1A-deficient cancers. Cancer Cell 35:2177–90.e8
    [Google Scholar]
  91. Okubo K, Isono M, Asano T, Sato A 2019. Metformin augments panobinostat's anti-bladder cancer activity by activating AMP-activated protein kinase. Transl. Oncol. 12:4669–82
    [Google Scholar]
  92. Oldham WM, Clish CB, Yang Y, Loscalzo J 2015. Hypoxia-mediated increases in l-2-hydroxyglutarate coordinate the metabolic response to reductive stress. Cell Metab 22:2291–303
    [Google Scholar]
  93. Pan M, Reid MA, Lowman XH, Kulkarni RP, Tran TQ et al. 2016. Regional glutamine deficiency in tumours promotes dedifferentiation through inhibition of histone demethylation. Nat. Cell Biol. 18:101090–101
    [Google Scholar]
  94. Park JW, Turcan Ş 2019. Epigenetic reprogramming for targeting IDH-mutant malignant gliomas. Cancers 11:101616
    [Google Scholar]
  95. Pavlova NN, Thompson CB. 2016. The emerging hallmarks of cancer metabolism. Cell Metab 23:127–47
    [Google Scholar]
  96. Pieroth R, Paver S, Day S, Lammersfeld C 2018. Folate and its impact on cancer risk. Curr. Nutr. Rep. 7:370–84
    [Google Scholar]
  97. Pogribny IP, Ross SA, Wise C, Pogribna M, Jones EA et al. 2006. Irreversible global DNA hypomethylation as a key step in hepatocarcinogenesis induced by dietary methyl deficiency. Mutat. Res. 593:1–280–87
    [Google Scholar]
  98. Potapova IA, El-Maghrabi MR, Doronin SV, Benjamin WB 2000. Phosphorylation of recombinant human ATP:citrate lyase by cAMP-dependent protein kinase abolishes homotropic allosteric regulation of the enzyme by citrate and increases the enzyme activity. Allosteric activation of atp:citrate lyase by phosphorylated sugars. Biochemistry 39:51169–79
    [Google Scholar]
  99. Qiu H, Jackson AL, Kilgore JE, Zhong Y, Chan LLY et al. 2015. JQ1 suppresses tumor growth through downregulating LDHA in ovarian cancer. Oncotarget 6:96915–30
    [Google Scholar]
  100. Raffel S, Falcone M, Kneisel N, Hansson J, Wang W et al. 2017. BCAT1 restricts αKG levels in AML stem cells leading to IDHmut-like DNA hypermethylation. Nature 551:7680384–88
    [Google Scholar]
  101. Raineri S, Mellor J. 2018. IDH1: linking metabolism and epigenetics. Front. Genet. 9:493
    [Google Scholar]
  102. Reid MA, Dai Z, Locasale JW 2017. The impact of cellular metabolism on chromatin dynamics and epigenetics. Nat. Cell Biol. 19:111298–306
    [Google Scholar]
  103. Reina-Campos M, Linares JF, Duran A, Metallo CM, Moscat J, Diaz-Meco MT 2019. Increased serine and one-carbon pathway metabolism by PKCλ/ι deficiency promotes neuroendocrine prostate cancer. Cancer Cell 35:3385–400.e9
    [Google Scholar]
  104. Rios Garcia M, Steinbauer B, Srivastava K, Singhal M, Mattijssen F et al. 2017. Acetyl-CoA carboxylase 1-dependent protein acetylation controls breast cancer metastasis and recurrence. Cell Metab 26:6842–55.e5
    [Google Scholar]
  105. Sabari BR, Zhang D, Allis CD, Zhao Y 2017. Metabolic regulation of gene expression through histone acylations. Nat. Rev. Mol. Cell Biol. 18:290–101
    [Google Scholar]
  106. Saffie R, Zhou N, Rolland D, Önder Ö, Basrur V et al. 2020. FBXW7 triggers degradation of KMT2D to favor growth of diffuse large B-cell lymphoma cells. Cancer Res 80:122498–511
    [Google Scholar]
  107. Sakamoto A, Hino S, Nagaoka K, Anan K, Takase R et al. 2015. Lysine demethylase LSD1 coordinates glycolytic and mitochondrial metabolism in hepatocellular carcinoma cells. Cancer Res 75:71445–56
    [Google Scholar]
  108. Sanderson SM, Gao X, Dai Z, Locasale JW 2019. Methionine metabolism in health and cancer: a nexus of diet and precision medicine. Nat. Rev. Cancer 19:11625–37
    [Google Scholar]
  109. Schug ZT, Peck B, Jones DT, Zhang Q, Grosskurth S et al. 2015. Acetyl-CoA synthetase 2 promotes acetate utilization and maintains cancer cell growth under metabolic stress. Cancer Cell 27:157–71
    [Google Scholar]
  110. Sciacovelli M, Gonçalves E, Johnson TI, Zecchini VR, Da Costa ASH et al. 2016. Fumarate is an epigenetic modifier that elicits epithelial-to-mesenchymal transition. Nature 537:7621544–47
    [Google Scholar]
  111. Sdelci S, Rendeiro AF, Rathert P, You W, Lin JMG et al. 2019. MTHFD1 interaction with BRD4 links folate metabolism to transcriptional regulation. Nat. Genet. 51:6990–98
    [Google Scholar]
  112. Sebastián C, Zwaans BMM, Silberman DM, Gymrek M, Goren A et al. 2012. The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism. Cell 151:61185–99
    [Google Scholar]
  113. Selak MA, Armour SM, MacKenzie ED, Boulahbel H, Watson DG et al. 2005. Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-α prolyl hydroxylase. Cancer Cell 7:177–85
    [Google Scholar]
  114. Seltzer MJ, Bennett BD, Joshi AD, Gao P, Thomas AG et al. 2010. Inhibition of glutaminase preferentially slows growth of glioma cells with mutant IDH1. Cancer Res 70:228981–87
    [Google Scholar]
  115. Senapati P, Kato H, Lee M, Leung A, Thai C et al. 2019. Hyperinsulinemia promotes aberrant histone acetylation in triple-negative breast cancer. Epigenet. Chromatin 12:44
    [Google Scholar]
  116. Sharif T, Ahn DG, Liu RZ, Pringle E, Martell E et al. 2016. The NAD+ salvage pathway modulates cancer cell viability via p73. Cell Death Differ 23:4669–80
    [Google Scholar]
  117. Shenoy N, Bhagat TD, Cheville J, Lohse C, Bhattacharyya S et al. 2019. Ascorbic acid-induced TET activation mitigates adverse hydroxymethylcytosine loss in renal cell carcinoma. J. Clin. Investig. 129:41612–25
    [Google Scholar]
  118. Shenoy N, Bhagat TD, Nieves E, Stenson M, Lawson J et al. 2017. Upregulation of TET activity with ascorbic acid induces epigenetic modulation of lymphoma cells. Blood Cancer J 7:7e587
    [Google Scholar]
  119. Shenoy N, Vallumsetla N, Zou Y, Galeas JN, Shrivastava M et al. 2015. Role of DNA methylation in renal cell carcinoma. J. Hematol. Oncol. 8:88
    [Google Scholar]
  120. Shi L, Tu BP. 2015. Acetyl-CoA and the regulation of metabolism: mechanisms and consequences. Curr. Opin. Cell Biol. 33:125–31
    [Google Scholar]
  121. Shim EH, Livi CB, Rakheja D, Tan J, Benson D et al. 2014. l-2-hydroxyglutarate: an epigenetic modifier and putative oncometabolite in renal cancer. Cancer Discov 4:111290–98
    [Google Scholar]
  122. Shimazu T, Hirschey MD, Newman J, He W, Shirakawa K et al. 2013. Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science 339:6116211–14
    [Google Scholar]
  123. Sivanand S, Rhoades S, Jiang Q, Lee JV, Benci J et al. 2017. Nuclear acetyl-CoA production by ACLY promotes homologous recombination. Mol. Cell 67:2252–65.e6
    [Google Scholar]
  124. Sivanand S, Viney I, Wellen KE 2018. Spatiotemporal control of acetyl-CoA metabolism in chromatin regulation. Trends Biochem. Sci. 43:161–74
    [Google Scholar]
  125. Song J, Medline A, Mason JB, Gallinger S, Kim YI 2000. Effects of dietary folate on intestinal tumorigenesis in the apcMin mouse. Cancer Res 60:195434–40
    [Google Scholar]
  126. Stathis A, Bertoni F. 2018. BET proteins as targets for anticancer treatment. Cancer Discov 8:124–36
    [Google Scholar]
  127. Stuani L, Sabatier M, Sarry JE 2019. Exploiting metabolic vulnerabilities for personalized therapy in acute myeloid leukemia. BMC Biol 17:57
    [Google Scholar]
  128. Sun RC, Dukhande VV, Zhou Z, Young LEA, Emanuelle S et al. 2019. Nuclear glycogenolysis modulates histone acetylation in human non-small cell lung cancers. Cell Metab 30:5903–16.e7
    [Google Scholar]
  129. Sutendra G, Kinnaird A, Dromparis P, Paulin R, Stenson TH et al. 2014. A nuclear pyruvate dehydrogenase complex is important for the generation of acetyl-CoA and histone acetylation. Cell 158:184–97
    [Google Scholar]
  130. Tajan M, Vousden KH. 2020. Dietary approaches to cancer therapy. Cancer Cell 37:6767–85
    [Google Scholar]
  131. Thakur BK, Dittrich T, Chandra P, Becker A, Lippka Y et al. 2012. Inhibition of NAMPT pathway by FK866 activates the function of p53 in HEK293T cells. Biochem. Biophys. Res. Commun. 424:3371–77
    [Google Scholar]
  132. Tran TQ, Hanse EA, Habowski AN, Li H, Ishak Gabra MB et al. 2020. α-Ketoglutarate attenuates Wnt signaling and drives differentiation in colorectal cancer. Nat. Cancer 1:3345–58
    [Google Scholar]
  133. Trefely S, Lovell CD, Snyder NW, Wellen KE 2020. Compartmentalised acyl-CoA metabolism and roles in chromatin regulation. Mol. Metab. 38:100941
    [Google Scholar]
  134. Tsang FHC, Law CT, Tang TCC, Cheng CLH, Chin DWC et al. 2019. Aberrant super-enhancer landscape in human hepatocellular carcinoma. Hepatology 69:62502–17
    [Google Scholar]
  135. Tummala KS, Gomes AL, Yilmaz M, Graña O, Bakiri L et al. 2014. Inhibition of de novo NAD+ synthesis by oncogenic URI causes liver tumorigenesis through DNA damage. Cancer Cell 26:6826–39
    [Google Scholar]
  136. Ulanovskaya OA, Zuhl AM, Cravatt BF 2013. NNMT promotes epigenetic remodeling in cancer by creating a metabolic methylation sink. Nat. Chem. Biol. 9:5300–6
    [Google Scholar]
  137. Vander Heiden MG, DeBerardinis RJ 2017. NNMT promotes epigenetic remodeling in cancer by creating a metabolic methylation sink. Cell 168:4657–69
    [Google Scholar]
  138. Wanders D, Hobson K, Ji X 2020. Methionine restriction and cancer biology. Nutrients 12:3684
    [Google Scholar]
  139. Wang Y, Zhang J, Ren S, Hu L, Zhou C et al. 2019. Branched-chain amino acid metabolic reprogramming orchestrates drug resistance to EGFR tyrosine kinase inhibitors. Cell Rep 28:512–25
    [Google Scholar]
  140. Ward PS, Patel J, Wise DR, Abdel-Wahab O, Bennett BD et al. 2010. The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting α-ketoglutarate to 2-hydroxyglutarate. Cancer Cell 17:3225–34
    [Google Scholar]
  141. Warner M, Gustafsson JA. 2014. On estrogen, cholesterol metabolism, and breast cancer. N. Engl. J. Med. 370:6572–73
    [Google Scholar]
  142. White PJ, McGarrah RW, Grimsrud PA, Tso SC, Yang WH et al. 2018. The BCKDH kinase and phosphatase integrate BCAA and lipid metabolism via regulation of ATP-citrate lyase. Cell Metab 27:61281–93.e7
    [Google Scholar]
  143. Wu D, Hu D, Chen H, Shi G, Fetahu IS et al. 2018a. Glucose-regulated phosphorylation of TET2 by AMPK reveals a pathway linking diabetes to cancer. Nature 559:7715637–41
    [Google Scholar]
  144. Wu Q, Madany P, Dobson JR, Schnabl JM, Sharma S et al. 2016. The BRG1 chromatin remodeling enzyme links cancer cell metabolism and proliferation. Oncotarget 7:2538270–81
    [Google Scholar]
  145. Wu X, Wu Y, He L, Wu L, Wang X, Liu Z 2018b. Effects of the intestinal microbial metabolite butyrate on the development of colorectal cancer. J. Cancer 9:142510–17
    [Google Scholar]
  146. Yong C, Stewart GD, Frezza C 2020. Oncometabolites in renal cancer. Nat. Rev. Nephrol. 16:3156–72
    [Google Scholar]
  147. Zagato E, Pozzi C, Bertocchi A, Schioppa T, Saccheri F et al. 2020. Endogenous murine microbiota member Faecalibaculum rodentium and its human homologue protect from intestinal tumour growth. Nat. Microbiol. 5:3511–24
    [Google Scholar]
  148. Zaware N, Zhou MM. 2019. Bromodomain biology and drug discovery. Nat. Struct. Mol. Biol. 26:10870–79
    [Google Scholar]
  149. Zhang Y, Shi J, Liu X, Feng L, Gong Z et al. 2018. BAP1 links metabolic regulation of ferroptosis to tumour suppression. Nat. Cell Biol. 20:101181–92
    [Google Scholar]
  150. Zheng Q, Omans ND, Leicher R, Osunsade A, Agustinus AS et al. 2019. Reversible histone glycation is associated with disease-related changes in chromatin architecture. Nat. Commun. 10:1289
    [Google Scholar]
  151. Zhong L, D'Urso A, Toiber D, Sebastian C, Henry RE et al. 2010. The histone deacetylase Sirt6 regulates glucose homeostasis via Hif1α. Cell 140:2280–93
    [Google Scholar]
/content/journals/10.1146/annurev-cancerbio-070820-035832
Loading
/content/journals/10.1146/annurev-cancerbio-070820-035832
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error