Proteins moonlighting in tumor metabolism and epigenetics

PDF(1796 KB)
PDF(1796 KB)
Frontiers of Medicine ›› 2021, Vol. 15 ›› Issue (3) : 383-403. DOI: 10.1007/s11684-020-0818-1
REVIEW

作者信息 +

Proteins moonlighting in tumor metabolism and epigenetics

Author information +
History +

Abstract

Cancer development is a complicated process controlled by the interplay of multiple signaling pathways and restrained by oxygen and nutrient accessibility in the tumor microenvironment. High plasticity in using diverse nutrients to adapt to metabolic stress is one of the hallmarks of cancer cells. To respond to nutrient stress and to meet the requirements for rapid cell proliferation, cancer cells reprogram metabolic pathways to take up more glucose and coordinate the production of energy and intermediates for biosynthesis. Such actions involve gene expression and activity regulation by the moonlighting function of oncoproteins and metabolic enzymes. The signalmoonlighting proteinmetabolism axis facilitates the adaptation of tumor cells under varying environment conditions and can be therapeutically targeted for cancer treatment.

Keywords

moonlighting function / tumor metabolism / epigenetics

引用本文

导出引用
. . Frontiers of Medicine. 2021, 15(3): 383-403 https://doi.org/10.1007/s11684-020-0818-1

参考文献

[1]
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144(5): 646–674
CrossRef ADS Pubmed Google scholar
[2]
Warburg O. On the origin of cancer cells. Science 1956; 123(3191): 309–314
CrossRef ADS Pubmed Google scholar
[3]
Allison KE, Coomber BL, Bridle BW. Metabolic reprogramming in the tumour microenvironment: a hallmark shared by cancer cells and T lymphocytes. Immunology 2017; 152(2): 175–184
CrossRef ADS Pubmed Google scholar
[4]
Rodrigues MF, Obre E, de Melo FH, Santos GC Jr, Galina A, Jasiulionis MG, Rossignol R, Rumjanek FD, Amoêdo ND. Enhanced OXPHOS, glutaminolysis and β-oxidation constitute the metastatic phenotype of melanoma cells. Biochem J 2016; 473(6): 703–715
CrossRef ADS Pubmed Google scholar
[5]
Caro P, Kishan AU, Norberg E, Stanley IA, Chapuy B, Ficarro SB, Polak K, Tondera D, Gounarides J, Yin H, Zhou F, Green MR, Chen L, Monti S, Marto JA, Shipp MA, Danial NN. Metabolic signatures uncover distinct targets in molecular subsets of diffuse large B cell lymphoma. Cancer Cell 2012; 22(4): 547–560
CrossRef ADS Pubmed Google scholar
[6]
Liu Y, Zuckier LS, Ghesani NV. Dominant uptake of fatty acid over glucose by prostate cells: a potential new diagnostic and therapeutic approach. Anticancer Res 2010; 30(2): 369–374
Pubmed
[7]
Lazar I, Clement E, Dauvillier S, Milhas D, Ducoux-Petit M, LeGonidec S, Moro C, Soldan V, Dalle S, Balor S, Golzio M, Burlet-Schiltz O, Valet P, Muller C, Nieto L. Adipocyte exosomes promote melanoma aggressiveness through fatty acid oxidation: a novel mechanism linking obesity and cancer. Cancer Res 2016; 76(14): 4051–4057
CrossRef ADS Pubmed Google scholar
[8]
Nieman KM, Kenny HA, Penicka CV, Ladanyi A, Buell-Gutbrod R, Zillhardt MR, Romero IL, Carey MS, Mills GB, Hotamisligil GS, Yamada SD, Peter ME, Gwin K, Lengyel E. Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. Nat Med 2011; 17(11): 1498–1503
CrossRef ADS Pubmed Google scholar
[9]
Cao Y. Adipocyte and lipid metabolism in cancer drug resistance. J Clin Invest 2019; 129(8): 3006–3017
CrossRef ADS Pubmed Google scholar
[10]
Iwamoto H, Abe M, Yang Y, Cui D, Seki T, Nakamura M, Hosaka K, Lim S, Wu J, He X, Sun X, Lu Y, Zhou Q, Shi W, Torimura T, Nie G, Li Q, Cao Y. Cancer lipid metabolism confers antiangiogenic drug resistance. Cell Metab 2018; 28(1): 104–117.e5
CrossRef ADS Pubmed Google scholar
[11]
Ward PS, Thompson CB. Metabolic reprogramming: a cancer hallmark even Warburg did not anticipate. Cancer Cell 2012; 21(3): 297–308
CrossRef ADS Pubmed Google scholar
[12]
Reina-Campos M, Moscat J, Diaz-Meco M. Metabolism shapes the tumor microenvironment. Curr Opin Cell Biol 2017; 48: 47–53
CrossRef ADS Pubmed Google scholar
[13]
Boukouris AE, Zervopoulos SD, Michelakis ED. Metabolic enzymes moonlighting in the nucleus: metabolic regulation of gene transcription. Trends Biochem Sci 2016; 41(8): 712–730
CrossRef ADS Pubmed Google scholar
[14]
Li M, Zhang CS, Zong Y, Feng JW, Ma T, Hu M, Lin Z, Li X, Xie C, Wu Y, Jiang D, Li Y, Zhang C, Tian X, Wang W, Yang Y, Chen J, Cui J, Wu YQ, Chen X, Liu QF, Wu J, Lin SY, Ye Z, Liu Y, Piao HL, Yu L, Zhou Z, Xie XS, Hardie DG, Lin SC. Transient receptor potential V channels are essential for glucose sensing by aldolase and AMPK. Cell Metab 2019; 30(3): 508–524.e12
CrossRef ADS Google scholar
[15]
Huangyang P, Li F, Lee P, Nissim I, Weljie AM, Mancuso A, Li B, Keith B, Yoon SS, Simon MC. Fructose-1,6-bisphosphatase 2 inhibits sarcoma progression by restraining mitochondrial biogenesis. Cell Metab 2020; 31(1): 174–188.e7
CrossRef ADS Pubmed Google scholar
[16]
Xu D, Wang Z, Xia Y, Shao F, Xia W, Wei Y, Li X, Qian X, Lee JH, Du L, Zheng Y, Lv G, Leu JS, Wang H, Xing D, Liang T, Hung MC, Lu Z. The gluconeogenic enzyme PCK1 phosphorylates INSIG1/2 for lipogenesis. Nature 2020; 580(7804): 530–535
CrossRef ADS Pubmed Google scholar
[17]
Fernández-Medarde A, Santos E. Ras in cancer and developmental diseases. Genes Cancer 2011; 2(3): 344–358
CrossRef ADS Pubmed Google scholar
[18]
Kerr EM, Gaude E, Turrell FK, Frezza C, Martins CP. Mutant Kras copy number defines metabolic reprogramming and therapeutic susceptibilities. Nature 2016; 531(7592): 110–113
CrossRef ADS Pubmed Google scholar
[19]
Cox AD, Der CJ. Ras history: the saga continues. Small GTPases 2010; 1(1): 2–27
CrossRef ADS Pubmed Google scholar
[20]
Simanshu DK, Nissley DV, McCormick F. RAS proteins and their regulators in human disease. Cell 2017; 170(1): 17–33
CrossRef ADS Pubmed Google scholar
[21]
Hallin J, Engstrom LD, Hargis L, Calinisan A, Aranda R, Briere DM, Sudhakar N, Bowcut V, Baer BR, Ballard JA, Burkard MR, Fell JB, Fischer JP, Vigers GP, Xue Y, Gatto S, Fernandez-Banet J, Pavlicek A, Velastagui K, Chao RC, Barton J, Pierobon M, Baldelli E, Patricoin EF 3rd, Cassidy DP, Marx MA, Rybkin II, Johnson ML, Ou SI, Lito P, Papadopoulos KP, Jänne PA, Olson P, Christensen JG. The KRASG12C inhibitor MRTX849 provides insight toward therapeutic susceptibility of KRAS-mutant cancers in mouse models and patients. Cancer Discov 2020; 10(1): 54–71
CrossRef ADS Pubmed Google scholar
[22]
Kimmelman AC. Metabolic dependencies in RAS-driven cancers. Clin Cancer Res 2015; 21(8): 1828–1834
CrossRef ADS Pubmed Google scholar
[23]
Ying H, Kimmelman AC, Lyssiotis CA, Hua S, Chu GC, Fletcher-Sananikone E, Locasale JW, Son J, Zhang H, Coloff JL, Yan H, Wang W, Chen S, Viale A, Zheng H, Paik JH, Lim C, Guimaraes AR, Martin ES, Chang J, Hezel AF, Perry SR, Hu J, Gan B, Xiao Y, Asara JM, Weissleder R, Wang YA, Chin L, Cantley LC, DePinho RA. Oncogenic Kras maintains pancreatic tumors through regulation of anabolic glucose metabolism. Cell 2012; 149(3): 656–670
CrossRef ADS Pubmed Google scholar
[24]
Amendola CR, Mahaffey JP, Parker SJ, Ahearn IM, Chen WC, Zhou M, Court H, Shi J, Mendoza SL, Morten MJ, Rothenberg E, Gottlieb E, Wadghiri YZ, Possemato R, Hubbard SR, Balmain A, Kimmelman AC, Philips MR. KRAS4A directly regulates hexokinase 1. Nature 2019; 576(7787): 482–486
CrossRef ADS Pubmed Google scholar
[25]
Vousden KH, Ryan KM. p53 and metabolism. Nat Rev Cancer 2009; 9(10): 691–700
CrossRef ADS Pubmed Google scholar
[26]
Kawauchi K, Araki K, Tobiume K, Tanaka N. p53 regulates glucose metabolism through an IKK-NF-κB pathway and inhibits cell transformation. Nat Cell Biol 2008; 10(5): 611–618
CrossRef ADS Pubmed Google scholar
[27]
Chipuk JE, Kuwana T, Bouchier-Hayes L, Droin NM, Newmeyer DD, Schuler M, Green DR. Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science 2004; 303(5660): 1010–1014
CrossRef ADS Pubmed Google scholar
[28]
Marchenko ND, Wolff S, Erster S, Becker K, Moll UM. Monoubiquitylation promotes mitochondrial p53 translocation. EMBO J 2007; 26(4): 923–934
CrossRef ADS Pubmed Google scholar
[29]
Park JH, Zhuang J, Li J, Hwang PM. p53 as guardian of the mitochondrial genome. FEBS Lett 2016; 590(7): 924–934
CrossRef ADS Pubmed Google scholar
[30]
Jiang P, Du W, Wang X, Mancuso A, Gao X, Wu M, Yang X. p53 regulates biosynthesis through direct inactivation of glucose-6-phosphate dehydrogenase. Nat Cell Biol 2011; 13(3): 310–316
CrossRef ADS Pubmed Google scholar
[31]
Hillmer EJ, Zhang H, Li HS, Watowich SS. STAT3 signaling in immunity. Cytokine Growth Factor Rev 2016; 31: 1–15
CrossRef ADS Pubmed Google scholar
[32]
Bromberg JF, Wrzeszczynska MH, Devgan G, Zhao Y, Pestell RG, Albanese C, Darnell JE Jr. Stat3 as an oncogene. Cell 1999; 98(3): 295–303
CrossRef ADS Pubmed Google scholar
[33]
Levy DE, Lee CK. What does Stat3 do? J Clin Invest 2002; 109(9): 1143–1148
CrossRef ADS Pubmed Google scholar
[34]
Guanizo AC, Fernando CD, Garama DJ, Gough DJ. STAT3: a multifaceted oncoprotein. Growth Factors 2018; 36(1-2): 1–14
CrossRef ADS Pubmed Google scholar
[35]
Zhao S, Venkatasubbarao K, Lazor JW, Sperry J, Jin C, Cao L, Freeman JW. Inhibition of STAT3 Tyr705 phosphorylation by Smad4 suppresses transforming growth factor beta-mediated invasion and metastasis in pancreatic cancer cells. Cancer Res 2008; 68(11): 4221–4228
CrossRef ADS Pubmed Google scholar
[36]
Bollrath J, Phesse TJ, von Burstin VA, Putoczki T, Bennecke M, Bateman T, Nebelsiek T, Lundgren-May T, Canli O, Schwitalla S, Matthews V, Schmid RM, Kirchner T, Arkan MC, Ernst M, Greten FR. gp130-mediated Stat3 activation in enterocytes regulates cell survival and cell-cycle progression during colitis-associated tumorigenesis. Cancer Cell 2009; 15(2): 91–102
CrossRef ADS Pubmed Google scholar
[37]
Wegrzyn J, Potla R, Chwae YJ, Sepuri NB, Zhang Q, Koeck T, Derecka M, Szczepanek K, Szelag M, Gornicka A, Moh A, Moghaddas S, Chen Q, Bobbili S, Cichy J, Dulak J, Baker DP, Wolfman A, Stuehr D, Hassan MO, Fu XY, Avadhani N, Drake JI, Fawcett P, Lesnefsky EJ, Larner AC. Function of mitochondrial Stat3 in cellular respiration. Science 2009; 323(5915): 793–797
CrossRef ADS Pubmed Google scholar
[38]
Garama DJ, White CL, Balic JJ, Gough DJ. Mitochondrial STAT3: powering up a potent factor. Cytokine 2016; 87: 20–25
CrossRef ADS Pubmed Google scholar
[39]
Genini D, Brambilla L, Laurini E, Merulla J, Civenni G, Pandit S, D’Antuono R, Perez L, Levy DE, Pricl S, Carbone GM, Catapano CV. Mitochondrial dysfunction induced by a SH2 domain-targeting STAT3 inhibitor leads to metabolic synthetic lethality in cancer cells. Proc Natl Acad Sci USA 2017; 114(25): E4924–E4933
CrossRef ADS Pubmed Google scholar
[40]
Pelengaris S, Khan M. The many faces of c-MYC. Arch Biochem Biophys 2003; 416(2): 129–136
CrossRef ADS Pubmed Google scholar
[41]
Kuzyk A, Mai S. c-MYC-induced genomic instability. Cold Spring Harb Perspect Med 2014; 4(4): a014373
CrossRef ADS Pubmed Google scholar
[42]
Dang CV. MYC on the path to cancer. Cell 2012; 149(1): 22–35
CrossRef ADS Pubmed Google scholar
[43]
Kumari A, Folk WP, Sakamuro D. The dual roles of MYC in genomic instability and cancer chemoresistance. Genes (Basel) 2017; 8(6): E158
CrossRef ADS Pubmed Google scholar
[44]
Dejure FR, Eilers M. MYC and tumor metabolism: chicken and egg. EMBO J 2017; 36(23): 3409–3420
CrossRef ADS Pubmed Google scholar
[45]
Pavlova NN, Thompson CB. The emerging hallmarks of cancer metabolism. Cell Metab 2016; 23(1): 27–47
CrossRef ADS Pubmed Google scholar
[46]
Shim H, Dolde C, Lewis BC, Wu CS, Dang G, Jungmann RA, Dalla-Favera R, Dang CV. c-Myc transactivation of LDH-A: implications for tumor metabolism and growth. Proc Natl Acad Sci USA 1997; 94(13): 6658–6663
CrossRef ADS Pubmed Google scholar
[47]
Fang Y, Shen ZY, Zhan YZ, Feng XC, Chen KL, Li YS, Deng HJ, Pan SM, Wu DH, Ding Y. CD36 inhibits β-catenin/c-myc-mediated glycolysis through ubiquitination of GPC4 to repress colorectal tumorigenesis. Nat Commun 2019; 10(1): 3981
CrossRef ADS Pubmed Google scholar
[48]
David CJ, Chen M, Assanah M, Canoll P, Manley JL. HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer. Nature 2010; 463(7279): 364–368
CrossRef ADS Pubmed Google scholar
[49]
Lee KM, Giltnane JM, Balko JM, Schwarz LJ, Guerrero-Zotano AL, Hutchinson KE, Nixon MJ, Estrada MV, Sánchez V, Sanders ME, Lee T, Gómez H, Lluch A, Pérez-Fidalgo JA, Wolf MM, Andrejeva G, Rathmell JC, Fesik SW, Arteaga CL. MYC and MCL1 cooperatively promote chemotherapy-resistant breast cancer stem cells via regulation of mitochondrial oxidative phosphorylation. Cell Metab 2017; 26(4): 633–647.e7
CrossRef ADS Pubmed Google scholar
[50]
Pelicano H, Martin DS, Xu RH, Huang P. Glycolysis inhibition for anticancer treatment. Oncogene 2006; 25(34): 4633–4646
CrossRef ADS Pubmed Google scholar
[51]
Ali M, Rellos P, Cox TM. Hereditary fructose intolerance. J Med Genet 1998; 35(5): 353–365
CrossRef ADS Pubmed Google scholar
[52]
Chang YC, Yang YC, Tien CP, Yang CJ, Hsiao M. Roles of aldolase family genes in human cancers and diseases. Trends Endocrinol Metab 2018; 29(8): 549–559
CrossRef ADS Pubmed Google scholar
[53]
Rose IA, O’Connell EL. Studies on the interaction of aldolase with substrate analogues. J Biol Chem 1969; 244(1): 126–134
Pubmed
[54]
Zhang CS, Hawley SA, Zong Y, Li M, Wang Z, Gray A, Ma T, Cui J, Feng JW, Zhu M, Wu YQ, Li TY, Ye Z, Lin SY, Yin H, Piao HL, Hardie DG, Lin SC. Fructose-1,6-bisphosphate and aldolase mediate glucose sensing by AMPK. Nature 2017; 548(7665): 112–116
CrossRef ADS Pubmed Google scholar
[55]
Herzig S, Shaw RJ. AMPK: guardian of metabolism and mitochondrial homeostasis. Nat Rev Mol Cell Biol 2018; 19(2): 121–135
CrossRef ADS Pubmed Google scholar
[56]
Tristan C, Shahani N, Sedlak TW, Sawa A. The diverse functions of GAPDH: views from different subcellular compartments. Cell Signal 2011; 23(2): 317–323
CrossRef ADS Pubmed Google scholar
[57]
Yun J, Mullarky E, Lu C, Bosch KN, Kavalier A, Rivera K, Roper J, Chio II, Giannopoulou EG, Rago C, Muley A, Asara JM, Paik J, Elemento O, Chen Z, Pappin DJ, Dow LE, Papadopoulos N, Gross SS, Cantley LC. Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH. Science 2015; 350(6266): 1391–1396
CrossRef ADS Pubmed Google scholar
[58]
Rodríguez-Pascual F, Redondo-Horcajo M, Magán-Marchal N, Lagares D, Martínez-Ruiz A, Kleinert H, Lamas S. Glyceraldehyde-3-phosphate dehydrogenase regulates endothelin-1 expression by a novel, redox-sensitive mechanism involving mRNA stability. Mol Cell Biol 2008; 28(23): 7139–7155
CrossRef ADS Pubmed Google scholar
[59]
Hara MR, Agrawal N, Kim SF, Cascio MB, Fujimuro M, Ozeki Y, Takahashi M, Cheah JH, Tankou SK, Hester LD, Ferris CD, Hayward SD, Snyder SH, Sawa A. S-nitrosylated GAPDH initiates apoptotic cell death by nuclear translocation following Siah1 binding. Nat Cell Biol 2005; 7(7): 665–674
CrossRef ADS Pubmed Google scholar
[60]
Kornberg MD, Sen N, Hara MR, Juluri KR, Nguyen JV, Snowman AM, Law L, Hester LD, Snyder SH. GAPDH mediates nitrosylation of nuclear proteins. Nat Cell Biol 2010; 12(11): 1094–1100
CrossRef ADS Pubmed Google scholar
[61]
Sen N, Hara MR, Kornberg MD, Cascio MB, Bae BI, Shahani N, Thomas B, Dawson TM, Dawson VL, Snyder SH, Sawa A. Nitric oxide-induced nuclear GAPDH activates p300/CBP and mediates apoptosis. Nat Cell Biol 2008; 10(7): 866–873
CrossRef ADS Pubmed Google scholar
[62]
Colell A, Ricci JE, Tait S, Milasta S, Maurer U, Bouchier-Hayes L, Fitzgerald P, Guio-Carrion A, Waterhouse NJ, Li CW, Mari B, Barbry P, Newmeyer DD, Beere HM, Green DR. GAPDH and autophagy preserve survival after apoptotic cytochrome c release in the absence of caspase activation. Cell 2007; 129(5): 983–997
CrossRef ADS Pubmed Google scholar
[63]
Chang C, Su H, Zhang D, Wang Y, Shen Q, Liu B, Huang R, Zhou T, Peng C, Wong CC, Shen HM, Lippincott-Schwartz J, Liu W. AMPK-dependent phosphorylation of GAPDH triggers Sirt1 activation and is necessary for autophagy upon glucose starvation. Mol Cell 2015; 60(6): 930–940
CrossRef ADS Pubmed Google scholar
[64]
Zheng L, Roeder RG, Luo Y. S phase activation of the histone H2B promoter by OCA-S, a coactivator complex that contains GAPDH as a key component. Cell 2003; 114(2): 255–266
CrossRef ADS Pubmed Google scholar
[65]
Sirover MA. Subcellular dynamics of multifunctional protein regulation: mechanisms of GAPDH intracellular translocation. J Cell Biochem 2012; 113(7): 2193–2200
CrossRef ADS Pubmed Google scholar
[66]
Zhang Y, Yu G, Chu H, Wang X, Xiong L, Cai G, Liu R, Gao H, Tao B, Li W, Li G, Liang J, Yang W. Macrophage-associated PGK1 phosphorylation promotes aerobic glycolysis and tumorigenesis. Mol Cell 2018; 71(2): 201–215.e7
CrossRef ADS Pubmed Google scholar
[67]
Hu H, Zhu W, Qin J, Chen M, Gong L, Li L, Liu X, Tao Y, Yin H, Zhou H, Zhou L, Ye D, Ye Q, Gao D. Acetylation of PGK1 promotes liver cancer cell proliferation and tumorigenesis. Hepatology 2017; 65(2): 515–528
CrossRef ADS Pubmed Google scholar
[68]
Nie H, Ju H, Fan J, Shi X, Cheng Y, Cang X, Zheng Z, Duan X, Yi W. O-GlcNAcylation of PGK1 coordinates glycolysis and TCA cycle to promote tumor growth. Nat Commun 2020; 11(1): 36
CrossRef ADS Pubmed Google scholar
[69]
Li X, Jiang Y, Meisenhelder J, Yang W, Hawke DH, Zheng Y, Xia Y, Aldape K, He J, Hunter T, Wang L, Lu Z. Mitochondria-translocated PGK1 functions as a protein kinase to coordinate glycolysis and the TCA cycle in tumorigenesis. Mol Cell 2016; 61(5): 705–719
CrossRef ADS Pubmed Google scholar
[70]
Qian X, Li X, Shi Z, Xia Y, Cai Q, Xu D, Tan L, Du L, Zheng Y, Zhao D, Zhang C, Lorenzi PL, You Y, Jiang BH, Jiang T, Li H, Lu Z. PTEN suppresses glycolysis by dephosphorylating and inhibiting autophosphorylated PGK1. Mol Cell 2019; 76(3): 516–527.e7
CrossRef ADS Pubmed Google scholar
[71]
Qian X, Li X, Cai Q, Zhang C, Yu Q, Jiang Y, Lee JH, Hawke D, Wang Y, Xia Y, Zheng Y, Jiang BH, Liu DX, Jiang T, Lu Z. Phosphoglycerate kinase 1 phosphorylates beclin1 to induce autophagy. Mol Cell 2017; 65(5): 917–931.e6
CrossRef ADS Pubmed Google scholar
[72]
Qian X, Li X, Lu Z. Protein kinase activity of the glycolytic enzyme PGK1 regulates autophagy to promote tumorigenesis. Autophagy 2017; 13(7): 1246–1247
CrossRef ADS Pubmed Google scholar
[73]
Liang C, Shi S, Qin Y, Meng Q, Hua J, Hu Q, Ji S, Zhang B, Xu J, Yu XJ. Localisation of PGK1 determines metabolic phenotype to balance metastasis and proliferation in patients with SMAD4-negative pancreatic cancer. Gut 2020; 69(5): 888–900
CrossRef ADS Pubmed Google scholar
[74]
Dayton TL, Jacks T, Vander Heiden MG. PKM2, cancer metabolism, and the road ahead. EMBO Rep 2016; 17(12): 1721–1730
CrossRef ADS Pubmed Google scholar
[75]
Mazurek S. Pyruvate kinase type M2: a key regulator of the metabolic budget system in tumor cells. Int J Biochem Cell Biol 2011; 43(7): 969–980
CrossRef ADS Pubmed Google scholar
[76]
Sun Q, Chen X, Ma J, Peng H, Wang F, Zha X, Wang Y, Jing Y, Yang H, Chen R, Chang L, Zhang Y, Goto J, Onda H, Chen T, Wang MR, Lu Y, You H, Kwiatkowski D, Zhang H. Mammalian target of rapamycin up-regulation of pyruvate kinase isoenzyme type M2 is critical for aerobic glycolysis and tumor growth. Proc Natl Acad Sci USA 2011; 108(10): 4129–4134
CrossRef ADS Pubmed Google scholar
[77]
Christofk HR, Vander Heiden MG, Harris MH, Ramanathan A, Gerszten RE, Wei R, Fleming MD, Schreiber SL, Cantley LC. The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature 2008; 452(7184): 230–233
CrossRef ADS Pubmed Google scholar
[78]
Christofk HR, Vander Heiden MG, Wu N, Asara JM, Cantley LC. Pyruvate kinase M2 is a phosphotyrosine-binding protein. Nature 2008; 452(7184): 181–186
CrossRef ADS Pubmed Google scholar
[79]
Lv L, Li D, Zhao D, Lin R, Chu Y, Zhang H, Zha Z, Liu Y, Li Z, Xu Y, Wang G, Huang Y, Xiong Y, Guan KL, Lei QY. Acetylation targets the M2 isoform of pyruvate kinase for degradation through chaperone-mediated autophagy and promotes tumor growth. Mol Cell 2011; 42(6): 719–730
CrossRef ADS Pubmed Google scholar
[80]
Macintyre AN, Rathmell JC. PKM2 and the tricky balance of growth and energy in cancer. Mol Cell 2011; 42(6): 713–714
CrossRef ADS Pubmed Google scholar
[81]
Lv L, Xu YP, Zhao D, Li FL, Wang W, Sasaki N, Jiang Y, Zhou X, Li TT, Guan KL, Lei QY, Xiong Y. Mitogenic and oncogenic stimulation of K433 acetylation promotes PKM2 protein kinase activity and nuclear localization. Mol Cell 2013; 52(3): 340–352
CrossRef ADS Pubmed Google scholar
[82]
Yang W, Zheng Y, Xia Y, Ji H, Chen X, Guo F, Lyssiotis CA, Aldape K, Cantley LC, Lu Z. ERK1/2-dependent phosphorylation and nuclear translocation of PKM2 promotes the Warburg effect. Nat Cell Biol 2012; 14(12): 1295–1304
CrossRef ADS Pubmed Google scholar
[83]
Yang W, Xia Y, Ji H, Zheng Y, Liang J, Huang W, Gao X, Aldape K, Lu Z. Nuclear PKM2 regulates β-catenin transactivation upon EGFR activation. Nature 2011; 480(7375): 118–122
CrossRef ADS Pubmed Google scholar
[84]
Li S, Swanson SK, Gogol M, Florens L, Washburn MP, Workman JL, Suganuma T. Serine and SAM responsive complex SESAME regulates histone modification crosstalk by sensing cellular metabolism. Mol Cell 2015; 60(3): 408–421
CrossRef ADS Pubmed Google scholar
[85]
Yang W, Xia Y, Hawke D, Li X, Liang J, Xing D, Aldape K, Hunter T, Alfred Yung WK, Lu Z. PKM2 phosphorylates histone H3 and promotes gene transcription and tumorigenesis. Cell 2012; 150(4): 685–696
CrossRef ADS Pubmed Google scholar
[86]
Hsu MC, Hung WC. Pyruvate kinase M2 fuels multiple aspects of cancer cells: from cellular metabolism, transcriptional regulation to extracellular signaling. Mol Cancer 2018; 17(1): 35
CrossRef ADS Pubmed Google scholar
[87]
Gao X, Wang H, Yang JJ, Liu X, Liu ZR. Pyruvate kinase M2 regulates gene transcription by acting as a protein kinase. Mol Cell 2012; 45(5): 598–609
CrossRef ADS Pubmed Google scholar
[88]
Keller KE, Doctor ZM, Dwyer ZW, Lee YS. SAICAR induces protein kinase activity of PKM2 that is necessary for sustained proliferative signaling of cancer cells. Mol Cell 2014; 53(5): 700–709
CrossRef ADS Pubmed Google scholar
[89]
Luo W, Hu H, Chang R, Zhong J, Knabel M, O’Meally R, Cole RN, Pandey A, Semenza GL. Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1. Cell 2011; 145(5): 732–744
CrossRef ADS Pubmed Google scholar
[90]
Wang HJ, Hsieh YJ, Cheng WC, Lin CP, Lin YS, Yang SF, Chen CC, Izumiya Y, Yu JS, Kung HJ, Wang WC. JMJD5 regulates PKM2 nuclear translocation and reprograms HIF-1α-mediated glucose metabolism. Proc Natl Acad Sci USA 2014; 111(1): 279–284
CrossRef ADS Pubmed Google scholar
[91]
Demaria M, Poli V. PKM2, STAT3 and HIF-1α: the Warburg’s vicious circle. JAK-STAT 2012; 1(3): 194–196
CrossRef ADS Pubmed Google scholar
[92]
Azoitei N, Becher A, Steinestel K, Rouhi A, Diepold K, Genze F, Simmet T, Seufferlein T. PKM2 promotes tumor angiogenesis by regulating HIF-1α through NF-kB activation. Mol Cancer 2016; 15(1): 3
CrossRef ADS Pubmed Google scholar
[93]
Hosios AM, Fiske BP, Gui DY, Vander Heiden MG. Lack of evidence for PKM2 protein kinase activity. Mol Cell 2015; 59(5): 850–857
CrossRef ADS Pubmed Google scholar
[94]
Vander Heiden MG, Christofk HR, Schuman E, Subtelny AO, Sharfi H, Harlow EE, Xian J, Cantley LC. Identification of small molecule inhibitors of pyruvate kinase M2. Biochem Pharmacol 2010; 79(8): 1118–1124
CrossRef ADS Pubmed Google scholar
[95]
Wang Y, Hao F, Nan Y, Qu L, Na W, Jia C, Chen X. PKM2 inhibitor shikonin overcomes the cisplatin resistance in bladder cancer by inducing necroptosis. Int J Biol Sci 2018; 14(13): 1883–1891
CrossRef ADS Pubmed Google scholar
[96]
Chen J, Xie J, Jiang Z, Wang B, Wang Y, Hu X. Shikonin and its analogs inhibit cancer cell glycolysis by targeting tumor pyruvate kinase-M2. Oncogene 2011; 30(42): 4297–4306
CrossRef ADS Pubmed Google scholar
[97]
Kung C, Hixon J, Choe S, Marks K, Gross S, Murphy E, DeLaBarre B, Cianchetta G, Sethumadhavan S, Wang X, Yan S, Gao Y, Fang C, Wei W, Jiang F, Wang S, Qian K, Saunders J, Driggers E, Woo HK, Kunii K, Murray S, Yang H, Yen K, Liu W, Cantley LC, Vander Heiden MG, Su SM, Jin S, Salituro FG, Dang L. Small molecule activation of PKM2 in cancer cells induces serine auxotrophy. Chem Biol 2012; 19(9): 1187–1198
CrossRef ADS Pubmed Google scholar
[98]
Anastasiou D, Yu Y, Israelsen WJ, Jiang JK, Boxer MB, Hong BS, Tempel W, Dimov S, Shen M, Jha A, Yang H, Mattaini KR, Metallo CM, Fiske BP, Courtney KD, Malstrom S, Khan TM, Kung C, Skoumbourdis AP, Veith H, Southall N, Walsh MJ, Brimacombe KR, Leister W, Lunt SY, Johnson ZR, Yen KE, Kunii K, Davidson SM, Christofk HR, Austin CP, Inglese J, Harris MH, Asara JM, Stephanopoulos G, Salituro FG, Jin S, Dang L, Auld DS, Park HW, Cantley LC, Thomas CJ, Vander Heiden MG. Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis. Nat Chem Biol 2012; 8(10): 839–847
CrossRef ADS Pubmed Google scholar
[99]
Parnell KM, Foulks JM, Nix RN, Clifford A, Bullough J, Luo B, Senina A, Vollmer D, Liu J, McCarthy V, Xu Y, Saunders M, Liu XH, Pearce S, Wright K, O’Reilly M, McCullar MV, Ho KK, Kanner SB. Pharmacologic activation of PKM2 slows lung tumor xenograft growth. Mol Cancer Ther 2013; 12(8): 1453–1460
CrossRef ADS Pubmed Google scholar
[100]
Dong C, Yuan T, Wu Y, Wang Y, Fan TW, Miriyala S, Lin Y, Yao J, Shi J, Kang T, Lorkiewicz P, St Clair D, Hung MC, Evers BM, Zhou BP. Loss of FBP1 by Snail-mediated repression provides metabolic advantages in basal-like breast cancer. Cancer Cell 2013; 23(3): 316–331
CrossRef ADS Pubmed Google scholar
[101]
Zhang J, Wang J, Xing H, Li Q, Zhao Q, Li J. Down-regulation of FBP1 by ZEB1-mediated repression confers to growth and invasion in lung cancer cells. Mol Cell Biochem 2016; 411(1–2): 331–340
CrossRef ADS Pubmed Google scholar
[102]
Hirata H, Sugimachi K, Komatsu H, Ueda M, Masuda T, Uchi R, Sakimura S, Nambara S, Saito T, Shinden Y, Iguchi T, Eguchi H, Ito S, Terashima K, Sakamoto K, Hirakawa M, Honda H, Mimori K. Decreased expression of fructose-1,6-bisphosphatase associates with glucose metabolism and tumor progression in hepatocellular carcinoma. Cancer Res 2016; 76(11): 3265–3276
CrossRef ADS Pubmed Google scholar
[103]
Son B, Lee S, Kim H, Kang H, Jeon J, Jo S, Seong KM, Lee SJ, Youn H, Youn B. Decreased FBP1 expression rewires metabolic processes affecting aggressiveness of glioblastoma. Oncogene 2020; 39(1): 36–49
CrossRef ADS Pubmed Google scholar
[104]
Li B, Qiu B, Lee DS, Walton ZE, Ochocki JD, Mathew LK, Mancuso A, Gade TP, Keith B, Nissim I, Simon MC. Fructose-1,6-bisphosphatase opposes renal carcinoma progression. Nature 2014; 513(7517): 251–255
CrossRef ADS Pubmed Google scholar
[105]
Lu C, Ren C, Yang T, Sun Y, Qiao P, Wang D, Lv S, Yu Z. A noncanonical role of fructose-1, 6-bisphosphatase 1 is essential for inhibition of Notch1 in breast cancer. Mol Cancer Res 2020; 18(5): 787–796
CrossRef ADS Pubmed Google scholar
[106]
Cong J, Wang X, Zheng X, Wang D, Fu B, Sun R, Tian Z, Wei H. Dysfunction of natural killer cells by FBP1-induced inhibition of glycolysis during lung cancer progression. Cell Metab 2018; 28(2): 243–255.e5
CrossRef ADS Pubmed Google scholar
[107]
Burgess SC, He T, Yan Z, Lindner J, Sherry AD, Malloy CR, Browning JD, Magnuson MA. Cytosolic phosphoenolpyruvate carboxykinase does not solely control the rate of hepatic gluconeogenesis in the intact mouse liver. Cell Metab 2007; 5(4): 313–320
CrossRef ADS Pubmed Google scholar
[108]
Méndez-Lucas A, Hyroššová P, Novellasdemunt L, Viñals F, Perales JC. Mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M) is a pro-survival, endoplasmic reticulum (ER) stress response gene involved in tumor cell adaptation to nutrient availability. J Biol Chem 2014; 289(32): 22090–22102
CrossRef ADS Pubmed Google scholar
[109]
Matés JM, Campos-Sandoval JA, Santos-Jiménez JL, Márquez J. Dysregulation of glutaminase and glutamine synthetase in cancer. Cancer Lett 2019; 467: 29–39
CrossRef ADS Pubmed Google scholar
[110]
Mishra P, Chan DC. Metabolic regulation of mitochondrial dynamics. J Cell Biol 2016; 212(4): 379–387
CrossRef ADS Pubmed Google scholar
[111]
Maycotte P, Marín-Hernández A, Goyri-Aguirre M, Anaya-Ruiz M, Reyes-Leyva J, Cortés-Hernández P. Mitochondrial dynamics and cancer. Tumour Biol 2017; 39(5): 1010428317698391
CrossRef ADS Pubmed Google scholar
[112]
Cai WF, Zhang C, Wu YQ, Zhuang G, Ye Z, Zhang CS, Lin SC. Glutaminase GLS1 senses glutamine availability in a non-enzymatic manner triggering mitochondrial fusion. Cell Res 2018; 28(8): 865–867
CrossRef ADS Pubmed Google scholar
[113]
Stillman TJ, Baker PJ, Britton KL, Rice DW. Conformational flexibility in glutamate dehydrogenase: role of water in substrate recognition and catalysis. J Mol Biol 1993; 234(4): 1131–1139
CrossRef ADS Pubmed Google scholar
[114]
Zaganas I, Spanaki C, Plaitakis A. Expression of human GLUD2 glutamate dehydrogenase in human tissues: functional implications. Neurochem Int 2012; 61(4): 455–462
CrossRef ADS Pubmed Google scholar
[115]
Michaelidis TM, Tzimagiorgis G, Moschonas NK, Papamatheakis J. The human glutamate dehydrogenase gene family: gene organization and structural characterization. Genomics 1993; 16(1): 150–160
CrossRef ADS Pubmed Google scholar
[116]
Jin L, Li D, Alesi GN, Fan J, Kang HB, Lu Z, Boggon TJ, Jin P, Yi H, Wright ER, Duong D, Seyfried NT, Egnatchik R, DeBerardinis RJ, Magliocca KR, He C, Arellano ML, Khoury HJ, Shin DM, Khuri FR, Kang S. Glutamate dehydrogenase 1 signals through antioxidant glutathione peroxidase 1 to regulate redox homeostasis and tumor growth. Cancer Cell 2015; 27(2): 257–270
CrossRef ADS Pubmed Google scholar
[117]
Fedeles BI, Singh V, Delaney JC, Li D, Essigmann JM. The AlkB family of Fe(II)/α-ketoglutarate-dependent dioxygenases: repairing nucleic acid alkylation damage and beyond. J Biol Chem 2015; 290(34): 20734–20742
CrossRef ADS Pubmed Google scholar
[118]
Yang C, Ko B, Hensley CT, Jiang L, Wasti AT, Kim J, Sudderth J, Calvaruso MA, Lumata L, Mitsche M, Rutter J, Merritt ME, DeBerardinis RJ. Glutamine oxidation maintains the TCA cycle and cell survival during impaired mitochondrial pyruvate transport. Mol Cell 2014; 56(3): 414–424
CrossRef ADS Pubmed Google scholar
[119]
Jin L, Chun J, Pan C, Kumar A, Zhang G, Ha Y, Li D, Alesi GN, Kang Y, Zhou L, Yu WM, Magliocca KR, Khuri FR, Qu CK, Metallo C, Owonikoko TK, Kang S. The PLAG1–GDH1 axis promotes anoikis resistance and tumor metastasis through CamKK2–AMPK signaling in LKB1-deficient lung cancer. Mol Cell 2018; 69(1): 87–99.e7
CrossRef ADS Pubmed Google scholar
[120]
Wang X, Liu R, Qu X, Yu H, Chu H, Zhang Y, Zhu W, Wu X, Gao H, Tao B, Li W, Liang J, Li G, Yang W. α-ketoglutarate-activated NF-κB signaling promotes compensatory glucose uptake and brain tumor development. Mol Cell 2019; 76(1): 148–162.e7
CrossRef ADS Pubmed Google scholar
[121]
Di Conza G, Tsai CH, Ho PC. Fifty shades of α-ketoglutarate on cellular programming. Mol Cell 2019; 76(1): 1–3
CrossRef ADS Pubmed Google scholar
[122]
Diggle CP, Shires M, Leitch D, Brooke D, Carr IM, Markham AF, Hayward BE, Asipu A, Bonthron DT. Ketohexokinase: expression and localization of the principal fructose-metabolizing enzyme. J Histochem Cytochem 2009; 57(8): 763–774
CrossRef ADS Pubmed Google scholar
[123]
Ishimoto T, Lanaspa MA, Le MT, Garcia GE, Diggle CP, Maclean PS, Jackman MR, Asipu A, Roncal-Jimenez CA, Kosugi T, Rivard CJ, Maruyama S, Rodriguez-Iturbe B, Sánchez-Lozada LG, Bonthron DT, Sautin YY, Johnson RJ. Opposing effects of fructokinase C and A isoforms on fructose-induced metabolic syndrome in mice. Proc Natl Acad Sci USA 2012; 109(11): 4320–4325
CrossRef ADS Pubmed Google scholar
[124]
Li X, Qian X, Lu Z. Fructokinase A acts as a protein kinase to promote nucleotide synthesis. Cell Cycle 2016; 15(20): 2689–2690
CrossRef ADS Pubmed Google scholar
[125]
Li X, Qian X, Peng LX, Jiang Y, Hawke DH, Zheng Y, Xia Y, Lee JH, Cote G, Wang H, Wang L, Qian CN, Lu Z. A splicing switch from ketohexokinase-C to ketohexokinase-A drives hepatocellular carcinoma formation. Nat Cell Biol 2016; 18(5): 561–571
CrossRef ADS Pubmed Google scholar
[126]
Xu D, Li X, Shao F, Lv G, Lv H, Lee JH, Qian X, Wang Z, Xia Y, Du L, Zheng Y, Wang H, Lyu J, Lu Z. The protein kinase activity of fructokinase A specifies the antioxidant responses of tumor cells by phosphorylating p62. Sci Adv 2019; 5(4): eaav4570
CrossRef ADS Pubmed Google scholar
[127]
Ippolito L, Morandi A, Giannoni E, Chiarugi P. Lactate: a metabolic driver in the tumour landscape. Trends Biochem Sci 2019; 44(2): 153–166
CrossRef ADS Pubmed Google scholar
[128]
Zhao D, Zou SW, Liu Y, Zhou X, Mo Y, Wang P, Xu YH, Dong B, Xiong Y, Lei QY, Guan KL. Lysine-5 acetylation negatively regulates lactate dehydrogenase A and is decreased in pancreatic cancer. Cancer Cell 2013; 23(4): 464–476
CrossRef ADS Pubmed Google scholar
[129]
Fantin VR, St-Pierre J, Leder P. Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance. Cancer Cell 2006; 9(6): 425–434
CrossRef ADS Pubmed Google scholar
[130]
Rosalki SB, Wilkinson JH. Reduction of α-ketobutyrate by human serum. Nature 1960; 188(4756): 1110–1111
CrossRef ADS Pubmed Google scholar
[131]
Liu Y, Guo JZ, Liu Y, Wang K, Ding W, Wang H, Liu X, Zhou S, Lu XC, Yang HB, Xu C, Gao W, Zhou L, Wang YP, Hu W, Wei Y, Huang C, Lei QY. Nuclear lactate dehydrogenase A senses ROS to produce α-hydroxybutyrate for HPV-induced cervical tumor growth. Nat Commun 2018; 9(1): 4429
CrossRef ADS Pubmed Google scholar
[132]
Intlekofer AM, Wang B, Liu H, Shah H, Carmona-Fontaine C, Rustenburg AS, Salah S, Gunner MR, Chodera JD, Cross JR, Thompson CB. L-2-Hydroxyglutarate production arises from noncanonical enzyme function at acidic pH. Nat Chem Biol 2017; 13(5): 494–500
CrossRef ADS Pubmed Google scholar
[133]
Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ, Friedman H, Friedman A, Reardon D, Herndon J, Kinzler KW, Velculescu VE, Vogelstein B, Bigner DD. IDH1 and IDH2 mutations in gliomas. N Engl J Med 2009; 360(8): 765–773
CrossRef ADS Pubmed Google scholar
[134]
Kang MR, Kim MS, Oh JE, Kim YR, Song SY, Seo SI, Lee JY, Yoo NJ, Lee SH. Mutational analysis of IDH1 codon 132 in glioblastomas and other common cancers. Int J Cancer 2009; 125(2): 353–355
CrossRef ADS Pubmed Google scholar
[135]
Nobusawa S, Yokoo H. IDH1/2 mutations in gliomas. Brain Nerve 2011; 63(12): 1378–1386
Pubmed
[136]
Mardis ER, Ding L, Dooling DJ, Larson DE, McLellan MD, Chen K, Koboldt DC, Fulton RS, Delehaunty KD, McGrath SD, Fulton LA, Locke DP, Magrini VJ, Abbott RM, Vickery TL, Reed JS, Robinson JS, Wylie T, Smith SM, Carmichael L, Eldred JM, Harris CC, Walker J, Peck JB, Du F, Dukes AF, Sanderson GE, Brummett AM, Clark E, McMichael JF, Meyer RJ, Schindler JK, Pohl CS, Wallis JW, Shi X, Lin L, Schmidt H, Tang Y, Haipek C, Wiechert ME, Ivy JV, Kalicki J, Elliott G, Ries RE, Payton JE, Westervelt P, Tomasson MH, Watson MA, Baty J, Heath S, Shannon WD, Nagarajan R, Link DC, Walter MJ, Graubert TA, DiPersio JF, Wilson RK, Ley TJ. Recurring mutations found by sequencing an acute myeloid leukemia genome. N Engl J Med 2009; 361(11): 1058–1066
CrossRef ADS Pubmed Google scholar
[137]
Borger DR, Tanabe KK, Fan KC, Lopez HU, Fantin VR, Straley KS, Schenkein DP, Hezel AF, Ancukiewicz M, Liebman HM, Kwak EL, Clark JW, Ryan DP, Deshpande V, Dias-Santagata D, Ellisen LW, Zhu AX, Iafrate AJ. Frequent mutation of isocitrate dehydrogenase (IDH)1 and IDH2 in cholangiocarcinoma identified through broad-based tumor genotyping. Oncologist 2012; 17(1): 72–79
CrossRef ADS Pubmed Google scholar
[138]
Yang H, Ye D, Guan KL, Xiong Y. IDH1 and IDH2 mutations in tumorigenesis: mechanistic insights and clinical perspectives. Clin Cancer Res 2012; 18(20): 5562–5571
CrossRef ADS Pubmed Google scholar
[139]
Ward PS, Patel J, Wise DR, Abdel-Wahab O, Bennett BD, Coller HA, Cross JR, Fantin VR, Hedvat CV, Perl AE, Rabinowitz JD, Carroll M, Su SM, Sharp KA, Levine RL, Thompson CB. The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting α-ketoglutarate to 2-hydroxyglutarate. Cancer Cell 2010; 17(3): 225–234
CrossRef ADS Pubmed Google scholar
[140]
Reitman ZJ, Parsons DW, Yan H. IDH1 and IDH2: not your typical oncogenes. Cancer Cell 2010; 17(3): 215–216
CrossRef ADS Pubmed Google scholar
[141]
Dang L, White DW, Gross S, Bennett BD, Bittinger MA, Driggers EM, Fantin VR, Jang HG, Jin S, Keenan MC, Marks KM, Prins RM, Ward PS, Yen KE, Liau LM, Rabinowitz JD, Cantley LC, Thompson CB, Vander Heiden MG, Su SM. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 2009; 462(7274): 739–744
CrossRef ADS Pubmed Google scholar
[142]
Xu W, Yang H, Liu Y, Yang Y, Wang P, Kim SH, Ito S, Yang C, Wang P, Xiao MT, Liu LX, Jiang WQ, Liu J, Zhang JY, Wang B, Frye S, Zhang Y, Xu YH, Lei QY, Guan KL, Zhao SM, Xiong Y. Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases. Cancer Cell 2011; 19(1): 17–30
CrossRef ADS Pubmed Google scholar
[143]
Lu C, Ward PS, Kapoor GS, Rohle D, Turcan S, Abdel-Wahab O, Edwards CR, Khanin R, Figueroa ME, Melnick A, Wellen KE, O’Rourke DM, Berger SL, Chan TA, Levine RL, Mellinghoff IK, Thompson CB. IDH mutation impairs histone demethylation and results in a block to cell differentiation. Nature 2012; 483(7390): 474–478
CrossRef ADS Pubmed Google scholar
[144]
Zhu H, Zhang Y, Chen J, Qiu J, Huang K, Wu M, Xia C. IDH1 R132H mutation enhances cell migration by activating AKT− mTOR signaling pathway, but sensitizes cells to 5-FU treatment as NADPH and GSH are reduced. PLoS One 2017; 12(1): e0169038
CrossRef ADS Pubmed Google scholar
[145]
Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Siu IM, Gallia GL, Olivi A, McLendon R, Rasheed BA, Keir S, Nikolskaya T, Nikolsky Y, Busam DA, Tekleab H, Diaz LA Jr, Hartigan J, Smith DR, Strausberg RL, Marie SK, Shinjo SM, Yan H, Riggins GJ, Bigner DD, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B, Velculescu VE, Kinzler KW. An integrated genomic analysis of human glioblastoma multiforme. Science 2008; 321(5897): 1807–1812
CrossRef ADS Pubmed Google scholar
[146]
Loenarz C, Schofield CJ. Expanding chemical biology of 2-oxoglutarate oxygenases. Nat Chem Biol 2008; 4(3): 152–156
CrossRef ADS Pubmed Google scholar
[147]
Reiter-Brennan C, Semmler L, Klein A. The effects of 2-hydroxyglutarate on the tumorigenesis of gliomas. Contemp Oncol (Pozn) 2018; 22(4): 215–222
CrossRef ADS Pubmed Google scholar
[148]
Wang P, Wu J, Ma S, Zhang L, Yao J, Hoadley KA, Wilkerson MD, Perou CM, Guan KL, Ye D, Xiong Y. Oncometabolite D-2-hydroxyglutarate inhibits ALKBH DNA repair enzymes and sensitizes IDH mutant cells to alkylating agents. Cell Rep 2015; 13(11): 2353–2361
CrossRef ADS Pubmed Google scholar
[149]
Yogev O, Yogev O, Singer E, Shaulian E, Goldberg M, Fox TD, Pines O. Fumarase: a mitochondrial metabolic enzyme and a cytosolic/nuclear component of the DNA damage response. PLoS Biol 2010; 8(3): e1000328
CrossRef ADS Pubmed Google scholar
[150]
Leshets M, Silas YBH, Lehming N, Pines O. Fumarase: from the TCA cycle to DNA damage response and tumor suppression. Front Mol Biosci 2018; 5: 68
CrossRef ADS Pubmed Google scholar
[151]
Xiao M, Yang H, Xu W, Ma S, Lin H, Zhu H, Liu L, Liu Y, Yang C, Xu Y, Zhao S, Ye D, Xiong Y, Guan KL. Inhibition of α-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(12): 1326–1338
CrossRef ADS Pubmed Google scholar
[152]
Jiang Y, Qian X, Shen J, Wang Y, Li X, Liu R, Xia Y, Chen Q, Peng G, Lin SY, Lu Z. Local generation of fumarate promotes DNA repair through inhibition of histone H3 demethylation. Nat Cell Biol 2015; 17(9): 1158–1168
CrossRef ADS Pubmed Google scholar
[153]
Wang T, Yu Q, Li J, Hu B, Zhao Q, Ma C, Huang W, Zhuo L, Fang H, Liao L, Eugene Chin Y, Jiang Y. O-GlcNAcylation of fumarase maintains tumour growth under glucose deficiency. Nat Cell Biol 2017; 19(7): 833–843
CrossRef ADS Pubmed Google scholar
[154]
Lin R, Tao R, Gao X, Li T, Zhou X, Guan KL, Xiong Y, Lei QY. Acetylation stabilizes ATP-citrate lyase to promote lipid biosynthesis and tumor growth. Mol Cell 2013; 51(4): 506–518
CrossRef ADS Pubmed Google scholar
[155]
Wellen KE, Hatzivassiliou G, Sachdeva UM, Bui TV, Cross JR, Thompson CB. ATP-citrate lyase links cellular metabolism to histone acetylation. Science 2009; 324(5930): 1076–1080
CrossRef ADS Pubmed Google scholar
[156]
Lee JV, Carrer A, Shah S, Snyder NW, Wei S, Venneti S, Worth AJ, Yuan ZF, Lim HW, Liu S, Jackson E, Aiello NM, Haas NB, Rebbeck TR, Judkins A, Won KJ, Chodosh LA, Garcia BA, Stanger BZ, Feldman MD, Blair IA, Wellen KE. Akt-dependent metabolic reprogramming regulates tumor cell histone acetylation. Cell Metab 2014; 20(2): 306–319
CrossRef ADS Pubmed Google scholar
[157]
Henderson B, Martin AC. Protein moonlighting: a new factor in biology and medicine. Biochem Soc Trans 2014; 42(6): 1671–1678
CrossRef ADS Pubmed Google scholar
[158]
Palsson-McDermott EM, Dyck L, Zasłona Z, Menon D, McGettrick AF, Mills KHG, O’Neill LA. Pyruvate kinase M2 is required for the expression of the immune checkpoint PD-L1 in immune cells and tumors. Front Immunol 2017; 8: 1300
CrossRef ADS Pubmed Google scholar

Acknowledgements

This work was supported by the Ministry of Science and Technology (No. 2019YFA0801703), the National Natural Science Foundation of China (Nos. 81790250, 81790253, 91959202, 81902823, and 81972620), and the Innovation Program of Shanghai Municipal Education Commission (No. N173606).

Compliance with ethics guidelines

Lei Lv and Qunying Lei declare that they have no conflict of interest. This manuscript is a review article and does not involve a research protocol requiring approval by the relevant institutional review board or ethics committee.

Open Access

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.

版权

2020 The Author(s) 2020. This article is published with open access at link.springer.com and journal.hep.com.cn
PDF(1796 KB)

Accesses

Citation

Detail

段落导航
相关文章

/