Metabolic recoding of epigenetics in cancer

Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009;324:1029–33. https://doi.org/10.1126/science.1160809. Pavlova NN, Thompson CB. The Emerging Hallmarks of Cancer Metabolism. Cell Metab. 2016;23:27–47. https://doi.org/10.1016/j.cmet.2015.12.006. Lin R, Zhou X, Huang W, Zhao D, Lv L, Xiong Y, et al. Acetylation control of cancer cell metabolism. Curr Pharm Des. 2014;20:2627–33. Qiu Z, Guo W, Wang Q, Chen Z, Huang S, Zhao F, et al. MicroRNA-124 reduces the pentose phosphate pathway and proliferation by targeting PRPS1 and RPIA mRNAs in human colorectal cancer cells. Gastroenterology. 2015;149(1587–98):e11. https://doi.org/10.1053/j.gastro.2015.07.050. DeBerardinis RJ, Chandel NS. Fundamentals of cancer metabolism. Sci Adv. 2016;2:e1600200. https://doi.org/10.1126/sciadv.1600200. Fan J, Lin R, Xia S, Chen D, Elf SE, Liu S, et al. Tetrameric Acetyl-CoA Acetyltransferase 1 is important for tumor growth. Mol Cell. 2016;64:859–74. https://doi.org/10.1016/j.molcel.2016.10.014. Wang J, Zhu ZH, Yang HB, Zhang Y, Zhao XN, Zhang M, et al. Cullin 3 targets methionine adenosyltransferase IIalpha for ubiquitylation-mediated degradation and regulates colorectal cancer cell proliferation. FEBS J. 2016;283:2390–402. https://doi.org/10.1111/febs.13759. Wang YP, Zhou W, Wang J, Huang X, Zuo Y, Wang TS, et al. Arginine methylation of MDH1 by CARM1 inhibits glutamine metabolism and suppresses pancreatic cancer. Mol Cell. 2016;64:673–87. https://doi.org/10.1016/j.molcel.2016.09.028. Zhang Y, Xu YY, Yao CB, Li JT, Zhao XN, Yang HB, et al. Acetylation targets HSD17B4 for degradation via the CMA pathway in response to estrone. Autophagy. 2017;13:538–53. https://doi.org/10.1080/15548627.2016.1268302. Guo W, Qiu Z, Wang Z, Wang Q, Tan N, Chen T, et al. MiR-199a-5p is negatively associated with malignancies and regulates glycolysis and lactate production by targeting hexokinase 2 in liver cancer. Hepatology. 2015;62:1132–44. https://doi.org/10.1002/hep.27929. Martinez-Outschoorn UE, Peiris-Pages M, Pestell RG, Sotgia F, Lisanti MP. Cancer metabolism: a therapeutic perspective. Nat Rev Clin Oncol. 2017;14:11–31. https://doi.org/10.1038/nrclinonc.2016.60. Boroughs LK, DeBerardinis RJ. Metabolic pathways promoting cancer cell survival and growth. Nat Cell Biol. 2015;17:351–9. https://doi.org/10.1038/ncb3124. Liang C, Qin Y, Zhang B, Ji S, Shi S, Xu W, et al. Metabolic plasticity in heterogeneous pancreatic ductal adenocarcinoma. Biochem Biophys Acta. 2016;1866:177–88. https://doi.org/10.1016/j.bbcan.2016.09.001. Zhong Z, Sanchez-Lopez E, Karin M. Autophagy, inflammation, and immunity: a troika governing cancer and its treatment. Cell. 2016;166:288–98. https://doi.org/10.1016/j.cell.2016.05.051. Kinnaird A, Zhao S, Wellen KE, Michelakis ED. Metabolic control of epigenetics in cancer. Nat Rev Cancer. 2016;16:694–707. https://doi.org/10.1038/nrc.2016.82. Ferrer CM, Lynch TP, Sodi VL, Falcone JN, Schwab LP, Peacock DL, et al. O-GlcNAcylation regulates cancer metabolism and survival stress signaling via regulation of the HIF-1 pathway. Mol Cell. 2014;54:820–31. https://doi.org/10.1016/j.molcel.2014.04.026. Kaelin WG Jr, McKnight SL. Influence of metabolism on epigenetics and disease. Cell. 2013;153:56–69. https://doi.org/10.1016/j.cell.2013.03.004. Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA Jr, Kinzler KW. Cancer Genome Landsc. Science. 2013;339:1546–58. https://doi.org/10.1126/science.1235122. Easwaran H, Tsai HC, Baylin SB. Cancer epigenetics: tumor heterogeneity, plasticity of stem-like states, and drug resistance. Mol Cell. 2014;54:716–27. https://doi.org/10.1016/j.molcel.2014.05.015. Du J, Johnson LM, Jacobsen SE, Patel DJ. DNA methylation pathways and their crosstalk with histone methylation. Nat Rev Mol Cell Biol. 2015;16:519–32. https://doi.org/10.1038/nrm4043. Baylin SB, Jones PA. A decade of exploring the cancer epigenome—biological and translational implications. Nat Rev Cancer. 2011;11:726–34. https://doi.org/10.1038/nrc3130. Katada S, Imhof A, Sassone-Corsi P. Connecting threads: epigenetics and metabolism. Cell. 2012;148:24–8. https://doi.org/10.1016/j.cell.2012.01.001. Rothbart SB, Strahl BD. Interpreting the language of histone and DNA modifications. Biochem Biophys Acta. 2014;1839:627–43. https://doi.org/10.1016/j.bbagrm.2014.03.001. Li T, Liu M, Feng X, Wang Z, Das I, Xu Y, et al. Glyceraldehyde-3-phosphate dehydrogenase is activated by lysine 254 acetylation in response to glucose signal. J Biol Chem. 2014;289:3775–85. https://doi.org/10.1074/jbc.M113.531640. Xu SN, Wang TS, Li X, Wang YP. SIRT2 activates G6PD to enhance NADPH production and promote leukaemia cell proliferation. Sci Rep. 2016;6:32734. https://doi.org/10.1038/srep32734. Cheng X. Structural and functional coordination of DNA and histone methylation. Cold Spring Harbor Perspect Biol. 2014. https://doi.org/10.1101/cshperspect.a018747. Fang R, Barbera AJ, Xu Y, Rutenberg M, Leonor T, Bi Q, et al. Human LSD2/KDM1b/AOF1 regulates gene transcription by modulating intragenic H3K4me2 methylation. Mol Cell. 2010;39:222–33. https://doi.org/10.1016/j.molcel.2010.07.008. Tsukada Y, Fang J, Erdjument-Bromage H, Warren ME, Borchers CH, Tempst P, et al. Histone demethylation by a family of JmjC domain-containing proteins. Nature. 2006;439:811–6. https://doi.org/10.1038/nature04433. Walport LJ, Hopkinson RJ, Chowdhury R, Schiller R, Ge W, Kawamura A, et al. Arginine demethylation is catalysed by a subset of JmjC histone lysine demethylases. Nat Commun. 2016;7:11974. https://doi.org/10.1038/ncomms11974. Blanc RS, Richard S. Arginine methylation: the coming of age. Mol Cell. 2017;65:8–24. https://doi.org/10.1016/j.molcel.2016.11.003. Smith ZD, Meissner A. DNA methylation: roles in mammalian development. Nat Rev Genet. 2013;14:204–20. https://doi.org/10.1038/nrg3354. Pastor WA, Aravind L, Rao A. TETonic shift: biological roles of TET proteins in DNA demethylation and transcription. Nat Rev Mol Cell Biol. 2013;14:341–56. https://doi.org/10.1038/nrm3589. Cai L, Sutter BM, Li B, Tu BP. Acetyl-CoA induces cell growth and proliferation by promoting the acetylation of histones at growth genes. Mol Cell. 2011;42:426–37. https://doi.org/10.1016/j.molcel.2011.05.004. Wellen KE, Hatzivassiliou G, Sachdeva UM, Bui TV, Cross JR, Thompson CB. ATP-citrate lyase links cellular metabolism to histone acetylation. Science. 2009;324:1076–80. https://doi.org/10.1126/science.1164097. Sutendra G, Kinnaird A, Dromparis P, Paulin R, Stenson TH, Haromy A, et al. A nuclear pyruvate dehydrogenase complex is important for the generation of acetyl-CoA and histone acetylation. Cell. 2014;158:84–97. https://doi.org/10.1016/j.cell.2014.04.046. Lin R, Tao R, Gao X, Li T, Zhou X, Guan KL, et al. Acetylation stabilizes ATP-citrate lyase to promote lipid biosynthesis and tumor growth. Mol Cell. 2013;51:506–18. https://doi.org/10.1016/j.molcel.2013.07.002. Saunders LR, Verdin E. Sirtuins: critical regulators at the crossroads between cancer and aging. Oncogene. 2007;26:5489–504. https://doi.org/10.1038/sj.onc.1210616. Lv L, Li D, Zhao D, Lin R, Chu Y, Zhang H, et al. Acetylation targets the M2 isoform of pyruvate kinase for degradation through chaperone-mediated autophagy and promotes tumor growth. Mol Cell. 2011;42:719–30. https://doi.org/10.1016/j.molcel.2011.04.025. Zhao D, Zou SW, Liu Y, Zhou X, Mo Y, Wang P, et al. Lysine-5 acetylation negatively regulates lactate dehydrogenase A and is decreased in pancreatic cancer. Cancer Cell. 2013;23:464–76. https://doi.org/10.1016/j.ccr.2013.02.005. Wang YP, Zhou LS, Zhao YZ, Wang SW, Chen LL, Liu LX, et al. Regulation of G6PD acetylation by SIRT2 and KAT9 modulates NADPH homeostasis and cell survival during oxidative stress. EMBO J. 2014;33:1304–20. https://doi.org/10.1002/embj.201387224. Yang HB, Xu YY, Zhao XN, Zou SW, Zhang Y, Zhang M, et al. Acetylation of MAT IIalpha represses tumour cell growth and is decreased in human hepatocellular cancer. Nat Commun. 2015;6:6973. https://doi.org/10.1038/ncomms7973. Cai J, Zuo Y, Wang T, Cao Y, Cai R, Chen FL, et al. A crucial role of SUMOylation in modulating Sirt6 deacetylation of H3 at lysine 56 and its tumor suppressive activity. Oncogene. 2016;35:4949–56. https://doi.org/10.1038/onc.2016.24. Kawahara TL, Michishita E, Adler AS, Damian M, Berber E, Lin M, et al. SIRT6 links histone H3 lysine 9 deacetylation to NF-κB-dependent gene expression and organismal life span. Cell. 2009;136:62–74. https://doi.org/10.1016/j.cell.2008.10.052. Barber MF, Michishita-Kioi E, Xi Y, Tasselli L, Kioi M, Moqtaderi Z, et al. SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation. Nature. 2012;487:114–8. https://doi.org/10.1038/nature11043. Vazquez BN, Thackray JK, Simonet NG, Kane-Goldsmith N, Martinez-Redondo P, Nguyen T, et al. SIRT7 promotes genome integrity and modulates non-homologous end joining DNA repair. EMBO J. 2016;35:1488–503. https://doi.org/10.15252/embj.201593499. Li L, Shi L, Yang S, Yan R, Zhang D, Yang J, et al. SIRT7 is a histone desuccinylase that functionally links to chromatin compaction and genome stability. Nat Commun. 2016;7:12235. https://doi.org/10.1038/ncomms12235. Feldman JL, Baeza J, Denu JM. Activation of the protein deacetylase SIRT6 by long-chain fatty acids and widespread deacylation by mammalian sirtuins. J Biol Chem. 2013;288:31350–6. https://doi.org/10.1074/jbc.C113.511261. Jiang H, Khan S, Wang Y, Charron G, He B, Sebastian C, et al. SIRT6 regulates TNF-alpha secretion through hydrolysis of long-chain fatty acyl lysine. Nature. 2013;496:110–3. https://doi.org/10.1038/nature12038. Carey BW, Finley LW, Cross JR, Allis CD, Thompson CB. Intracellular alpha-ketoglutarate maintains the pluripotency of embryonic stem cells. Nature. 2015;518:413–6. https://doi.org/10.1038/nature13981. Simpson NE, Tryndyak VP, Pogribna M, Beland FA, Pogribny IP. Modifying metabolically sensitive histone marks by inhibiting glutamine metabolism affects gene expression and alters cancer cell phenotype. Epigenetics. 2012;7:1413–20. https://doi.org/10.4161/epi.22713. Wilhelm JA, McCarty KS. The uptake and turnover of acetate in HeLa cell histone fractions. Cancer Res. 1970;30:418–25. Mashimo T, Pichumani K, Vemireddy V, Hatanpaa KJ, Singh DK, Sirasanagandla S, et al. Acetate is a bioenergetic substrate for human glioblastoma and brain metastases. Cell. 2014;159:1603–14. https://doi.org/10.1016/j.cell.2014.11.025. Comerford SA, Huang Z, Du X, Wang Y, Cai L, Witkiewicz AK, et al. Acetate dependence of tumors. Cell. 2014;159:1591–602. https://doi.org/10.1016/j.cell.2014.11.020. Schug ZT, Peck B, Jones DT, Zhang Q, Grosskurth S, Alam IS, et al. Acetyl-CoA synthetase 2 promotes acetate utilization and maintains cancer cell growth under metabolic stress. Cancer Cell. 2015;27:57–71. https://doi.org/10.1016/j.ccell.2014.12.002. Gao X, Lin SH, Ren F, Li JT, Chen JJ, Yao CB, et al. Acetate functions as an epigenetic metabolite to promote lipid synthesis under hypoxia. Nat Commun. 2016;7:11960. https://doi.org/10.1038/ncomms11960. Bulusu V, Tumanov S, Michalopoulou E, van den Broek NJ, MacKay G, Nixon C, et al. Acetate recapturing by nuclear acetyl-coa synthetase 2 prevents loss of histone acetylation during oxygen and serum limitation. Cell Rep. 2017;18:647–58. https://doi.org/10.1016/j.celrep.2016.12.055. Zhao S, Torres A, Henry RA, Trefely S, Wallace M, Lee JV, et al. ATP-citrate lyase controls a glucose-to-acetate metabolic switch. Cell Rep. 2016;17:1037–52. https://doi.org/10.1016/j.celrep.2016.09.069. McDonnell E, Crown SB, Fox DB, Kitir B, Ilkayeva OR, Olsen CA, et al. Lipids reprogram metabolism to become a major carbon source for histone acetylation. Cell Rep. 2016;17:1463–72. https://doi.org/10.1016/j.celrep.2016.10.012. Carrer A, Parris JL, Trefely S, Henry RA, Montgomery DC, Torres A, et al. Impact of a high-fat diet on tissue acyl-coa and histone acetylation levels. J Biol Chem. 2017;292:3312–22. https://doi.org/10.1074/jbc.M116.750620. Newman AC, Maddocks ODK. One-carbon metabolism in cancer. Br J Cancer. 2017;116:1499–504. https://doi.org/10.1038/bjc.2017.118. Teperino R, Schoonjans K, Auwerx J. Histone methyl transferases and demethylases; can they link metabolism and transcription? Cell Metab. 2010;12:321–7. https://doi.org/10.1016/j.cmet.2010.09.004. Panopoulos AD, Yanes O, Ruiz S, Kida YS, Diep D, Tautenhahn R, et al. The metabolome of induced pluripotent stem cells reveals metabolic changes occurring in somatic cell reprogramming. Cell Res. 2012;22:168–77. https://doi.org/10.1038/cr.2011.177. Shin HJ, Kim H, Oh S, Lee JG, Kee M, Ko HJ, et al. AMPK-SKP2-CARM1 signalling cascade in transcriptional regulation of autophagy. Nature. 2016;534:553–7. https://doi.org/10.1038/nature18014. Dang L, White DW, Gross S, Bennett BD, Bittinger MA, Driggers EM, et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature. 2009;462:739–44. https://doi.org/10.1038/nature08617. Xu W, Yang H, Liu Y, Yang Y, Wang P, Kim SH, et al. Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of alpha-ketoglutarate-dependent dioxygenases. Cancer Cell. 2011;19:17–30. https://doi.org/10.1016/j.ccr.2010.12.014. Lu C, Ward PS, Kapoor GS, Rohle D, Turcan S, Abdel-Wahab O, et al. IDH mutation impairs histone demethylation and results in a block to cell differentiation. Nature. 2012;483:474–8. https://doi.org/10.1038/nature10860. Wang Y, Xiao M, Chen X, Chen L, Xu Y, Lv L, et al. WT1 recruits TET2 to regulate its target gene expression and suppress leukemia cell proliferation. Mol Cell. 2015;57:662–73. https://doi.org/10.1016/j.molcel.2014.12.023. Mardis ER, Ding L, Dooling DJ, Larson DE, McLellan MD, Chen K, et al. Recurring mutations found by sequencing an acute myeloid leukemia genome. New Engl J Med. 2009;361:1058–66. https://doi.org/10.1056/NEJMoa0903840. Pollard PJ, Briere JJ, Alam NA, Barwell J, Barclay E, Wortham NC, et al. Accumulation of Krebs cycle intermediates and over-expression of HIF1alpha in tumours which result from germline FH and SDH mutations. Hum Mol Genet. 2005;14:2231–9. https://doi.org/10.1093/hmg/ddi227. Xiao M, Yang H, Xu W, Ma S, Lin H, Zhu H, et al. Inhibition of alpha-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors. Genes Dev. 2012;26:1326–38. https://doi.org/10.1101/gad.191056.112. Intlekofer AM, Dematteo RG, Venneti S, Finley LW, Lu C, Judkins AR, et al. Hypoxia induces production of L-2-hydroxyglutarate. Cell Metab. 2015;22:304–11. https://doi.org/10.1016/j.cmet.2015.06.023. Oldham WM, Clish CB, Yang Y, Loscalzo J. Hypoxia-mediated increases in L-2-hydroxyglutarate coordinate the metabolic response to reductive stress. Cell Metab. 2015;22:291–303. https://doi.org/10.1016/j.cmet.2015.06.021. Intlekofer AM, Wang B, Liu H, Shah H, Carmona-Fontaine C, Rustenburg AS, et al. L-2-hydroxyglutarate production arises from noncanonical enzyme function at acidic pH. Nat Chem Biol. 2017;13:494–500. https://doi.org/10.1038/nchembio.2307. Gerweck LE, Seetharaman K. Cellular pH gradient in tumor versus normal tissue: potential exploitation for the treatment of cancer. Cancer Res. 1996;56:1194–8. Hou H, Zhao Y, Li C, Wang M, Xu X, Jin Y. Single-cell pH imaging and detection for pH profiling and label-free rapid identification of cancer-cells. Sci Rep. 2017;7:1759. https://doi.org/10.1038/s41598-017-01956-1. Schartner EP, Henderson MR, Purdey M, Dhatrak D, Monro TM, Gill PG, et al. Cancer detection in human tissue samples using a fiber-tip pH probe. Cancer Res. 2016;76:6795–801. https://doi.org/10.1158/0008-5472.CAN-16-1285. Donohoe DR, Collins LB, Wali A, Bigler R, Sun W, Bultman SJ. The Warburg effect dictates the mechanism of butyrate-mediated histone acetylation and cell proliferation. Mol Cell. 2012;48:612–26. https://doi.org/10.1016/j.molcel.2012.08.033. Cancer Genome Atlas Research N,, et al, Ley TJ, Miller C, Ding L, Raphael BJ, Mungall AJ. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. New Engl J Med. 2013;368:2059–74. https://doi.org/10.1056/NEJMoa1301689. Wang JH, Chen WL, Li JM, Wu SF, Chen TL, Zhu YM, et al. Prognostic significance of 2-hydroxyglutarate levels in acute myeloid leukemia in China. Proc Natl Acad Sci USA. 2013;110:17017–22. https://doi.org/10.1073/pnas.1315558110. Chowdhury R, Yeoh KK, Tian YM, Hillringhaus L, Bagg EA, Rose NR, et al. The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases. EMBO Rep. 2011;12:463–9. https://doi.org/10.1038/embor.2011.43. Fan J, Krautkramer KA, Feldman JL, Denu JM. Metabolic regulation of histone post-translational modifications. ACS Chem Biol. 2015;10:95–108. https://doi.org/10.1021/cb500846u. Li X, Yu W, Qian X, Xia Y, Zheng Y, Lee JH, et al. Nucleus-translocated ACSS2 promotes gene transcription for lysosomal biogenesis and autophagy. Mol Cell. 2017;66(684–97):e9. https://doi.org/10.1016/j.molcel.2017.04.026. Wang T, Yu Q, Li J, Hu B, Zhao Q, Ma C, et al. O-GlcNAcylation of fumarase maintains tumour growth under glucose deficiency. Nat Cell Biol. 2017. https://doi.org/10.1038/ncb3562. Bowsher CG, Tobin AK. Compartmentation of metabolism within mitochondria and plastids. J Exp Bot. 2001;52:513–27. Rogers JK, Church GM. Genetically encoded sensors enable real-time observation of metabolite production. Proc Natl Acad Sci USA. 2016;113:2388–93. https://doi.org/10.1073/pnas.1600375113. Zhang Q, Liu X, Gao W, Li P, Hou J, Li J, et al. Differential regulation of the ten-eleven translocation (TET) family of dioxygenases by O-linked beta-N-acetylglucosamine transferase (OGT). J Biol Chem. 2014;289:5986–96. https://doi.org/10.1074/jbc.M113.524140. Koukourakis MI, Giatromanolaki A, Harris AL, Sivridis E. Comparison of metabolic pathways between cancer cells and stromal cells in colorectal carcinomas: a metabolic survival role for tumor-associated stroma. Cancer Res. 2006;66:632–7. https://doi.org/10.1158/0008-5472.CAN-05-3260. Ho PC, Bihuniak JD, Macintyre AN, Staron M, Liu X, Amezquita R, et al. Phosphoenolpyruvate is a metabolic checkpoint of anti-tumor T cell responses. Cell. 2015;162:1217–28. https://doi.org/10.1016/j.cell.2015.08.012. Wenes M, Shang M, Di Matteo M, Goveia J, Martin-Perez R, Serneels J, et al. Macrophage metabolism controls tumor blood vessel morphogenesis and metastasis. Cell Metab. 2016;24:701–15. https://doi.org/10.1016/j.cmet.2016.09.008. Dickson I. Pancreatic cancer: stromal-cancer cell crosstalk supports tumour metabolism. Nat Rev Gastroenterol Hepatol. 2016;13:558–9. https://doi.org/10.1038/nrgastro.2016.137. Brisson L, Banski P, Sboarina M, Dethier C, Danhier P, Fontenille MJ, et al. Lactate dehydrogenase B controls lysosome activity and autophagy in cancer. Cancer Cell. 2016;30:418–31. https://doi.org/10.1016/j.ccell.2016.08.005. Sousa CM, Biancur DE, Wang X, Halbrook CJ, Sherman MH, Zhang L, et al. Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion. Nature. 2016;536:479–83. https://doi.org/10.1038/nature19084. Lu C, Thompson CB. Metabolic regulation of epigenetics. Cell Metab. 2012;16:9–17. https://doi.org/10.1016/j.cmet.2012.06.001. Folmes CD, Dzeja PP, Nelson TJ, Terzic A. Metabolic plasticity in stem cell homeostasis and differentiation. Cell Stem Cell. 2012;11:596–606. https://doi.org/10.1016/j.stem.2012.10.002.