Clinical Nutrition Research

The Korean Society of Clinical Nutrition (한국임상영양학회)
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Links between Serine Biosynthesis Pathway and Epigenetics in Cancer Metabolism

  • Kim, HaEun (Department of Nutritional Science and Food Management, Ewha Womans University) ;
  • Park, Yoon Jung (Department of Nutritional Science and Food Management, Ewha Womans University)
  • Received : 2018.04.23
  • Accepted : 2018.07.19
  • Published : 2018.07.31
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Abstract

Cancer metabolism is considered as one of major cancer hallmarks. It is important to understand cancer-specific metabolic changes and its impact on cancer biology to identify therapeutic potentials. Among cancer-specific metabolic changes, a role of serine metabolism has been discovered in various cancer types. Upregulation of serine synthesis pathway (SSP) supports cell proliferation and metastasis. The change of serine metabolism is, in part, mediated by epigenetic modifiers, such as Euchromatic histone-lysine N-methyltransferase 2 and Lysine Demethylase 4C. On the other hand, SSP also influences epigenetic landscape such as methylation status of nucleic acids and histone proteins via affecting S-adenosyl methionine production. In the review, we highlight recent evidences on interactions between SSP and epigenetic regulation in cancer. It may provide an insight on roles and regulation of SSP in cancer metabolism and the potential of serine metabolism for cancer therapy.

Keywords

Acknowledgement

Supported by : National Research Foundation of Korea

References

  1. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011;144:646-74. https://doi.org/10.1016/j.cell.2011.02.013
  2. Carmeliet P, Dor Y, Herbert JM, Fukumura D, Brusselmans K, Dewerchin M, Neeman M, Bono F, Abramovitch R, Maxwell P, Koch CJ, Ratcliffe P, Moons L, Jain RK, Collen D, Keshert E. Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. Nature 1998;394:485-90. https://doi.org/10.1038/28867
  3. Bertout JA, Patel SA, Simon MC. The impact of O2 availability on human cancer. Nat Rev Cancer 2008;8:967-75. https://doi.org/10.1038/nrc2540
  4. Semenza GL. HIF-1: upstream and downstream of cancer metabolism. Curr Opin Genet Dev 2010;20:51-6. https://doi.org/10.1016/j.gde.2009.10.009
  5. Luengo A, Gui DY, Vander Heiden MG. Targeting metabolism for cancer therapy. Cell Chem Biol 2017;24:1161-80. https://doi.org/10.1016/j.chembiol.2017.08.028
  6. Mattaini KR, Sullivan MR, Vander Heiden MG. The importance of serine metabolism in cancer. J Cell Biol 2016;214:249-57. https://doi.org/10.1083/jcb.201604085
  7. Sharma S, Kelly TK, Jones PA. Epigenetics in cancer. Carcinogenesis 2010;31:27-36. https://doi.org/10.1093/carcin/bgp220
  8. Greenblatt M, Shubi P. Tumor angiogenesis: transfilter diffusion studies in the hamster by the transparent chamber technique. J Natl Cancer Inst 1968;41:111-24.
  9. 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
  10. Warburg O. On the origin of cancer cells. Science 1956;123:309-14. https://doi.org/10.1126/science.123.3191.309
  11. Pfeiffer T, Schuster S, Bonhoeffer S. Cooperation and competition in the evolution of ATP-producing pathways. Science 2001;292:504-7. https://doi.org/10.1126/science.1058079
  12. Zu XL, Guppy M. Cancer metabolism: facts, fantasy, and fiction. Biochem Biophys Res Commun 2004;313:459-65. https://doi.org/10.1016/j.bbrc.2003.11.136
  13. 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
  14. Locasale JW. Serine, glycine and one-carbon units: cancer metabolism in full circle. Nat Rev Cancer 2013;13:572-83. https://doi.org/10.1038/nrc3557
  15. Snell K. Enzymes of serine metabolism in normal, developing and neoplastic rat tissues. Adv Enzyme Regul 1984;22:325-400. https://doi.org/10.1016/0065-2571(84)90021-9
  16. Appaji Rao N, Ambili M, Jala VR, Subramanya HS, Savithri HS. Structure-function relationship in serine hydroxymethyltransferase. Biochim Biophys Acta 2003;1647:24-9. https://doi.org/10.1016/S1570-9639(03)00043-8
  17. Shane B, Stokstad EL. Vitamin B12-folate interrelationships. Annu Rev Nutr 1985;5:115-41. https://doi.org/10.1146/annurev.nu.05.070185.000555
  18. Stipanuk MH. Sulfur amino acid metabolism: pathways for production and removal of homocysteine and cysteine. Annu Rev Nutr 2004;24:539-77. https://doi.org/10.1146/annurev.nutr.24.012003.132418
  19. Stover PJ, Field MS. Trafficking of intracellular folates. Adv Nutr 2011;2:325-31. https://doi.org/10.3945/an.111.000596
  20. Amelio I, Cutruzzola F, Antonov A, Agostini M, Melino G. Serine and glycine metabolism in cancer. Trends Biochem Sci 2014;39:191-8. https://doi.org/10.1016/j.tibs.2014.02.004
  21. Cantoni GL. The nature of the active methyl donor formed enzymatically from L-methionine and adenosinetriphosphate. J Am Chem Soc 1952;74:2942-3.
  22. 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
  23. Chaneton B, Hillmann P, Zheng L, Martin AC, Maddocks OD, Chokkathukalam A, Coyle JE, Jankevics A, Holding FP, Vousden KH, Frezza C, O'Reilly M, Gottlieb E. Serine is a natural ligand and allosteric activator of pyruvate kinase M2. Nature 2012;491:458-62. https://doi.org/10.1038/nature11540
  24. Pompella A, Visvikis A, Paolicchi A, De Tata V, Casini AF. The changing faces of glutathione, a cellular protagonist. Biochem Pharmacol 2003;66:1499-503. https://doi.org/10.1016/S0006-2952(03)00504-5
  25. Snell K, Natsumeda Y, Weber G. The modulation of serine metabolism in hepatoma 3924A during different phases of cellular proliferation in culture. Biochem J 1987;245:609-12. https://doi.org/10.1042/bj2450609
  26. Pollari S, Kakonen SM, Edgren H, Wolf M, Kohonen P, Sara H, Guise T, Nees M, Kallioniemi O. Enhanced serine production by bone metastatic breast cancer cells stimulates osteoclastogenesis. Breast Cancer Res Treat 2011;125:421-30. https://doi.org/10.1007/s10549-010-0848-5
  27. Locasale JW, Grassian AR, Melman T, Lyssiotis CA, Mattaini KR, Bass AJ, Heffron G, Metallo CM, Muranen T, Sharfi H, Sasaki AT, Anastasiou D, Mullarky E, Vokes NI, Sasaki M, Beroukhim R, Stephanopoulos G, Ligon AH, Meyerson M, Richardson AL, Chin L, Wagner G, Asara JM, Brugge JS, Cantley LC, Vander Heiden MG. Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis. Nat Genet 2011;43:869-74. https://doi.org/10.1038/ng.890
  28. Snell K, Weber G. Enzymic imbalance in serine metabolism in rat hepatomas. Biochem J 1986;233:617-20. https://doi.org/10.1042/bj2330617
  29. Possemato R, Marks KM, Shaul YD, Pacold ME, Kim D, Birsoy K, Sethumadhavan S, Woo HK, Jang HG, Jha AK, Chen WW, Barrett FG, Stransky N, Tsun ZY, Cowley GS, Barretina J, Kalaany NY, Hsu PP, Ottina K, Chan AM, Yuan B, Garraway LA, Root DE, Mino-Kenudson M, Brachtel EF, Driggers EM, Sabatini DM. Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Nature 2011;476:346-50. https://doi.org/10.1038/nature10350
  30. Beroukhim R, Mermel CH, Porter D, Wei G, Raychaudhuri S, Donovan J, Barretina J, Boehm JS, Dobson J, Urashima M, Mc Henry KT, Pinchback RM, Ligon AH, Cho YJ, Haery L, Greulich H, Reich M, Winckler W, Lawrence MS, Weir BA, Tanaka KE, Chiang DY, Bass AJ, Loo A, Hoffman C, Prensner J, Liefeld T, Gao Q, Yecies D, Signoretti S, Maher E, Kaye FJ, Sasaki H, Tepper JE, Fletcher JA, Tabernero J, Baselga J, Tsao MS, Demichelis F, Rubin MA, Janne PA, Daly MJ, Nucera C, Levine RL, Ebert BL, Gabriel S, Rustgi AK, Antonescu CR, Ladanyi M, Letai A, Garraway LA, Loda M, Beer DG, True LD, Okamoto A, Pomeroy SL, Singer S, Golub TR, Lander ES, Getz G, Sellers WR, Meyerson M. The landscape of somatic copy-number alteration across human cancers. Nature 2010;463:899-905. https://doi.org/10.1038/nature08822
  31. Yoon S, Kim JG, Seo AN, Park SY, Kim HJ, Park JS, Choi GS, Jeong JY, Jun Y, Yoon GS, Kang BW. Clinical implication of serine metabolism-associated enzymes in colon cancer. Oncology 2015;89:351-9. https://doi.org/10.1159/000439571
  32. Liu J, Guo S, Li Q, Yang L, Xia Z, Zhang L, Huang Z, Zhang N. Phosphoglycerate dehydrogenase induces glioma cells proliferation and invasion by stabilizing forkhead box M1. J Neurooncol 2013;111:245-55. https://doi.org/10.1007/s11060-012-1018-x
  33. Jing Z, Heng W, Aiping D, Yafei Q, Shulan Z. Expression and clinical significance of phosphoglycerate dehydrogenase and squamous cell carcinoma antigen in cervical cancer. Int J Gynecol Cancer 2013;23:1465-9. https://doi.org/10.1097/IGC.0b013e3182a0c068
  34. Waddington CH. The epigenotype. 1942. Int J Epidemiol 2012;41:10-3. https://doi.org/10.1093/ije/dyr184
  35. Wu Ct, Morris JR. Genes, genetics, and epigenetics: a correspondence. Science 2001;293:1103-5. https://doi.org/10.1126/science.293.5532.1103
  36. Robertson KD. DNA methylation and human disease. Nat Rev Genet 2005;6:597-610.
  37. Reik W. Stability and flexibility of epigenetic gene regulation in mammalian development. Nature 2007;447:425-32. https://doi.org/10.1038/nature05918
  38. Kouzarides T. Chromatin modifications and their function. Cell 2007;128:693-705. https://doi.org/10.1016/j.cell.2007.02.005
  39. Flavahan WA, Gaskell E, Bernstein BE. Epigenetic plasticity and the hallmarks of cancer. Science 2017;357:eaal2380. https://doi.org/10.1126/science.aal2380
  40. Jones PA, Baylin SB. The fundamental role of epigenetic events in cancer. Nat Rev Genet 2002;3:415-28. https://doi.org/10.1038/nrg816
  41. Jones PA, Baylin SB. The epigenomics of cancer. Cell 2007;128:683-92. https://doi.org/10.1016/j.cell.2007.01.029
  42. Lindroth AM, Park YJ, Plass C. Epigenetic reprogramming in cancer. In: Meissner A, Walter J, editors. Epigenetic mechanisms in cellular reprogramming. Berlin: Springer; 2015. p. 193-223.
  43. Ley TJ, Ding L, Walter MJ, McLellan MD, Lamprecht T, Larson DE, Kandoth C, Payton JE, Baty J, Welch J, Harris CC, Lichti CF, Townsend RR, Fulton RS, Dooling DJ, Koboldt DC, Schmidt H, Zhang Q, Osborne JR, Lin L, O'Laughlin M, McMichael JF, Delehaunty KD, McGrath SD, Fulton LA, Magrini VJ, Vickery TL, Hundal J, Cook LL, Conyers JJ, Swift GW, Reed JP, Alldredge PA, Wylie T, Walker J, Kalicki J, Watson MA, Heath S, Shannon WD, Varghese N, Nagarajan R, Westervelt P, Tomasson MH, Link DC, Graubert TA, DiPersio JF, Mardis ER, Wilson RK. DNMT3A mutations in acute myeloid leukemia. N Engl J Med 2010;363:2424-33. https://doi.org/10.1056/NEJMoa1005143
  44. Varambally S, Dhanasekaran SM, Zhou M, Barrette TR, Kumar-Sinha C, Sanda MG, Ghosh D, Pienta KJ, Sewalt RG, Otte AP, Rubin MA, Chinnaiyan AM. The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature 2002;419:624-9. https://doi.org/10.1038/nature01075
  45. Kleer CG, Cao Q, Varambally S, Shen R, Ota I, Tomlins SA, Ghosh D, Sewalt RG, Otte AP, Hayes DF, Sabel MS, Livant D, Weiss SJ, Rubin MA, Chinnaiyan AM. EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. Proc Natl Acad Sci U S A 2003;100:11606-11. https://doi.org/10.1073/pnas.1933744100
  46. Hua KT, Wang MY, Chen MW, Wei LH, Chen CK, Ko CH, Jeng YM, Sung PL, Jan YH, Hsiao M, Kuo ML, Yen ML. The H3K9 methyltransferase G9a is a marker of aggressive ovarian cancer that promotes peritoneal metastasis. Mol Cancer 2014;13:189. https://doi.org/10.1186/1476-4598-13-189
  47. Casciello F, Al-Ejeh F, Kelly G, Brennan DJ, Ngiow SF, Young A, Stoll T, Windloch K, Hill MM, Smyth MJ, Gannon F, Lee JS. G9a drives hypoxia-mediated gene repression for breast cancer cell survival and tumorigenesis. Proc Natl Acad Sci U S A 2017;114:7077-82. https://doi.org/10.1073/pnas.1618706114
  48. Maddocks OD, Labuschagne CF, Adams PD, Vousden KH. Serine metabolism supports the methionine cycle and DNA/RNA methylation through de novo ATP synthesis in cancer cells. Mol Cell 2016;61:210-21. https://doi.org/10.1016/j.molcel.2015.12.014
  49. Kottakis F, Nicolay BN, Roumane A, Karnik R, Gu H, Nagle JM, Boukhali M, Hayward MC, Li YY, Chen T, Liesa M, Hammerman PS, Wong KK, Hayes DN, Shirihai OS, Dyson NJ, Haas W, Meissner A, Bardeesy N. LKB1 loss links serine metabolism to DNA methylation and tumorigenesis. Nature 2016;539:390-5. https://doi.org/10.1038/nature20132
  50. Shackelford DB, Shaw RJ. The LKB1-AMPK pathway: metabolism and growth control in tumour suppression. Nat Rev Cancer 2009;9:563-75. https://doi.org/10.1038/nrc2676
  51. Ding J, Li T, Wang X, Zhao E, Choi JH, Yang L, Zha Y, Dong Z, Huang S, Asara JM, Cui H, Ding HF. The histone H3 methyltransferase G9A epigenetically activates the serine-glycine synthesis pathway to sustain cancer cell survival and proliferation. Cell Metab 2013;18:896-907. https://doi.org/10.1016/j.cmet.2013.11.004
  52. DeNicola GM, Chen PH, Mullarky E, Sudderth JA, Hu Z, Wu D, Tang H, Xie Y, Asara JM, Huffman KE, Wistuba II, Minna JD, DeBerardinis RJ, Cantley LC. NRF2 regulates serine biosynthesis in non-small cell lung cancer. Nat Genet 2015;47:1475-81. https://doi.org/10.1038/ng.3421
  53. Zhao E, Ding J, Xia Y, Liu M, Ye B, Choi JH, Yan C, Dong Z, Huang S, Zha Y, Yang L, Cui H, Ding HF. KDM4C and ATF4 cooperate in transcriptional control of amino acid metabolism. Cell Reports 2016;14:506-19. https://doi.org/10.1016/j.celrep.2015.12.053
  54. Adams CM. Role of the transcription factor ATF4 in the anabolic actions of insulin and the anti-anabolic actions of glucocorticoids. J Biol Chem 2007;282:16744-53. https://doi.org/10.1074/jbc.M610510200

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