Metabolic Dysregulations and Epigenetics: A Bidirectional Interplay that Drives Tumor Progression
Abstract
:1. Introduction
2. As the Metabolic Rewiring Controls the Epigenome
2.1. Metabolites as Cofactors and/or Substrates of Epigenetic Players
2.2. Oncometabolites
2.3. Metabolic Enzymes Moonlighting in the Nucleus
3. As Epigenetics Control Metabolic Reprogramming
4. Metabolic/Epigenetic Changes Modify Tumor Microenvironments Promoting Immune Escape and Tumor Progression
5. Epigenetics/Metabolism Crosstalk: New Therapeutic Opportunities
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- Cairns, R.A.; Harris, I.S.; Mak, T.W. Regulation of cancer cell metabolism. Nat. Rev. Cancer 2011, 11, 85–95. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- DeBerardinis, R.J.; Chandel, N.S. Fundamentals of cancer metabolism. Sci. Adv. 2016. [Google Scholar] [CrossRef] [PubMed]
- Cantor, J.R.; Sabatini, D.M. Cancer cell metabolism: One hallmark, many faces. Cancer Discov. 2012, 2, 881–898. [Google Scholar] [CrossRef]
- Martín-Martín, N.; Carracedo, A.; Torrano, V. Metabolism and transcription in cancer: Merging two classic tales. Front. Cell Dev. Biol. 2018. [Google Scholar] [CrossRef] [PubMed]
- Pavlova, N.N.; Thompson, C.B. Perspective the emerging hallmarks of cancer metabolism. Cell Metab. 2016, 23, 27–47. [Google Scholar] [CrossRef] [PubMed]
- Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: The next generation. Cell 2011, 144, 646–674. [Google Scholar] [CrossRef] [PubMed]
- Matassa, D.S.; Amoroso, M.R.; Lu, H.; Avolio, R.; Arzeni, D.; Procaccini, C.; Faicchia, D.; Maddalena, F.; Simeon, V.; Agliarulo, I.; et al. Oxidative metabolism drives inflammation-induced platinum resistance in human ovarian cancer. Cell Death Differ. 2016, 23, 1542–1554. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Denise, C.; Paoli, P.; Calvani, M.; Taddei, M.L.; Giannoni, E.; Kopetz, S.; Kazmi, S.M.; Pia, M.M.; Pettazzoni, P.; Sacco, E.; et al. 5-Fluorouracil resistant colon cancer cells are addicted to OXPHOS to survive and enhance stem-like traits. Oncotarget 2015, 6, 41706–41721. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Liberti, M.V.; Locasale, J.W. The Warburg effect: How does it benefit cancer cells? Trends Biochem. Sci. 2016, 41, 211–218. [Google Scholar] [CrossRef] [PubMed]
- Owen, O.E.; Kalhan, S.C.; Hanson, R.W. The key role of anaplerosis and cataplerosis for citric acid cycle function. J. Biol. Chem. 2002, 277, 30409–30412. [Google Scholar] [CrossRef] [PubMed]
- Vander Heiden, M.G.; DeBerardinis, R.J. Understanding the intersections between metabolism and cancer biology. Cell 2017, 168, 657–669. [Google Scholar] [CrossRef] [PubMed]
- Etchegaray, J.; Mostoslavsky, R. Interplay between metabolism and epigenetics: A nuclear adaptation to environmental changes. Mol. Cell. 2016, 62, 695–711. [Google Scholar] [CrossRef] [PubMed]
- Biswas, S.; Rao, C.M. Epigenetic tools (the Writers, the Readers and the Erasers) and their implications in cancer therapy. Eur. J. Pharmacol. 2018, 837, 8–24. [Google Scholar] [CrossRef] [PubMed]
- Kinnaird, A.; Zhao, S.; Wellen, K.E.; Michelakis, E.D. Metabolic control of epigenetics in cancer. Nat. Rev. Cancer 2016, 16, 694–707. [Google Scholar] [CrossRef] [PubMed]
- Reid, M.A.; Dai, Z.; Locasale, J.W. The impact of cellular metabolism on chromatin dynamics and epigenetics. Nat. Cell Biol. 2017, 19, 1298–1306. [Google Scholar] [CrossRef] [PubMed]
- Campbell, S.L.; Wellen, K.E. Metabolic signaling to the nucleus in cancer review metabolic signaling to the nucleus in cancer. Mol. Cell. 2018, 71, 398–408. [Google Scholar] [CrossRef] [PubMed]
- Kim, J.; Yeom, Y.I. Metabolic signaling to epigenetic alterations in cancer. Biomol Ther. 2018, 26, 69–80. [Google Scholar] [CrossRef]
- Nebbioso, A.; Tambaro, F.P.; Aversana, C.D.; Altucci, L. Cancer epigenetics: Moving forward. PLoS Genet. 2018. [CrossRef]
- Sharma, S.; Kelly, T.K.; Jones, P.A. Epigenetics in cancer. Carcinogenesis 2010, 31, 27–36. [Google Scholar] [CrossRef]
- Flavahan, W.A.; Gaskell, E.; Bernstein, B.E. Epigenetic plasticity and the hallmarks of cancer. Science 2018. [Google Scholar] [CrossRef]
- Wong, C.C.; Qian, Y.; Yu, J. Interplay between epigenetics and metabolism in oncogenesis: Mechanisms and therapeutic approaches. Oncogene 2017, 36, 3359–3374. [Google Scholar] [CrossRef] [PubMed]
- Miranda-Gonçalves, V.; Lameirinhas, A.; Henrique, R.; Jerónimo, C. Metabolism and epigenetic interplay in cancer: Regulation and putative therapeutic targets. Front. Genet. 2018. [CrossRef] [PubMed]
- Boukouris, A.E.; Zervopoulos, S.D.; Michelakis, E.D. Metabolic enzymes moonlighting in the nucleus: Metabolic regulation of gene transcription. Trends Biochem. Sci. 2016, 41, 712–730. [Google Scholar] [CrossRef] [PubMed]
- Zhao, Z.; Wang, L.; Di, L. Compartmentation of metabolites in regulating epigenomes of cancer. Mol. Med. 2016, 22, 349–360. [Google Scholar] [CrossRef] [PubMed]
- Newman, A.C.; Maddocks, O.D.K. Serine and functional metabolites in cancer. Trends Cell Biol. 2017, 27, 645–657. [Google Scholar] [CrossRef] [PubMed]
- Mattaini, K.R.; Sullivan, M.R.; Vander Heiden, M.G. The importance of serine metabolism in cancer. J. Cell Biol. 2016, 214, 249–257. [Google Scholar] [CrossRef] [Green Version]
- Amelio, I.; Cutruzzola, F.; Agostini, M.; Melino, G. Serine and glycine metabolism in cancer. Trends Biochem. Sci. 2014, 39, 191–198. [Google Scholar] [CrossRef]
- Locasale, J.W. Serine, glycine and the one-carbon cycle: Cancer metabolism in full circle. Nat. Rev. Cancer 2013, 13, 572–583. [Google Scholar] [CrossRef]
- Luo, J.; Li, Y.; Wang, F.; Zhang, W.; Geng, X. S-Adenosylmethionine inhibits the growth of cancer cells by reversing the hypomethylation status of c-myc and H-ras in human gastric cancer and colon cancer. Int. J. Biol. Sci. 2010, 6, 784–795. [Google Scholar] [CrossRef]
- Ilisso, C.P.; Sapio, L.; Delle Cave, D.; Illiano, M.; Spina, A.; Cacciapuoti, G.; Naviglio, S.; Porcelli, M. S-adenosylmethionine affects ERK1/2 and Stat3 pathways and induces apoptosis in osteosarcoma cells. J. Cell Physiol. 2016, 231, 428–435. [Google Scholar] [CrossRef]
- Shukeir, N.; Stefanska, B.; Parashar, S.; Chik, F.; Arakelian, A.; Szyf, M.; Rabbani, S.A. Pharmacological methyl group donors block skeletal metastasis in vitro and in vivo. Br. J. Pharmacol. 2015, 172, 2769–2781. [Google Scholar] [CrossRef] [PubMed]
- Ilisso, C.P.; Delle Cave, D.; Mosca, L.; Pagano, M.; Coppola, A.; Mele, L.; Caraglia, M.; Cacciapuoti, G.; Porcelli, M. S-Adenosylmethionine regulates apoptosis and autophagy in MCF-7 breast cancer cells through the modulation of specific microRNAs. Cancer Cell Int. 2018. [Google Scholar] [CrossRef] [PubMed]
- Dai, Z.; Mentch, S.J.; Gao, X.; Nichenametla, S.N.; Locasale, J.W. Methionine metabolism influences genomic architecture and gene expression through H3K4me3 peak width. Nat. Commun. 2018. [Google Scholar] [CrossRef] [PubMed]
- Wellen, K.E.; Hatzivassiliou, G.; Sachdeva, U.M.; Bui, T.V.; Cross, J.R.; Thompson, C.B. ATP-citrate lyase links cellular metabolism to histone acetylation. Science 2009, 324, 1076–1080. [Google Scholar] [CrossRef] [PubMed]
- Lee, J.V.; Carrer, A.; Shah, S.; Snyder, N.W.; Wei, S.; Venneti, S.; Worth, A.J.; Yuan, Z.F.; Lim, H.W.; Liu, S.E.; et al. Akt-dependent metabolic reprogramming regulates tumor cell histone acetylation. Cell Metab. 2014, 20, 306–319. [Google Scholar] [CrossRef] [PubMed]
- Pietrocola, F.; Galluzzi, L.; Bravo-San Pedro, J.M.; Madeo, F.; Kroemer, G. Acetyl Coenzyme A: A central metabolite and second messenger. Cell Metab. 2015, 21, 805–821. [Google Scholar] [CrossRef] [PubMed]
- Sivanand, S.; Viney, I.; Wellen, K.E. Spatiotemporal control of acetyl-CoA metabolism in chromatin regulation. Trends Biochem. Sci. 2018, 43, 61–74. [Google Scholar] [CrossRef]
- Mullen, A.R.; Wheaton, W.W.; Jin, E.S.; Chen, P.H.; Sullivan, L.B.; Cheng, T.; Yang, Y.; Linehan, W.M.; Chandel, N.S.; DeBerardinis, R.J. Reductive carboxylation supports growth in tumour cells with defective mitochondria. Nature 2012, 481, 385–388. [Google Scholar] [CrossRef]
- McBrian, M.A.; Behbahan, I.S.; Ferrari, R.; Su, T.; Huang, T.W.; Li, K.; Hong, C.S.; Christofk, H.R.; Vogelauer, M.D.; Seligson, B.; et al. Histone acetylation regulates intracellular pH. Mol. Cell. 2013, 49, 310–321. [Google Scholar] [CrossRef]
- Erecińska, M.; Deas, J.; Silver, I.A. The effect of pH on glycolysis and phosphofructokinase activity in cultured cells and synaptosomes. J. Neurochem. 1995, 65, 2765–2772. [Google Scholar] [CrossRef]
- Shimazu, T.; Hirschey, M.D.; Newman, J.; He, W.; Shirakawa, K.; Le Moan, N.; Grueter, C.A.; Lim, H.; Saunders, L.R.; Stevens, R.D.; et al. Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science 2013, 339, 211–214. [Google Scholar] [CrossRef] [PubMed]
- Donohoe, D.R.; Collins, L.B.; Wali, A.; Bigler, R.; Sun, W.; Bultman, S.J. The Warburg effect dictates the mechanism of butyrate mediated histone acetylation and cell proliferation. Mol. Cell. 2012, 48, 612–626. [Google Scholar] [CrossRef] [PubMed]
- McDonough, M.A.; Loenarz, C.; Chowdhury, R.; Clifton, I.J.; Schofield, C.J. Structural studies on human 2-oxoglutarate dependent oxygenases. Curr. Opin. Struct. Biol. 2010, 20, 659–672. [Google Scholar] [CrossRef] [PubMed]
- Carey, B.W.; Finley, L.W.S.; Cross, J.R.; Allis, C.D.; Thompson, C.B. Intracellular α-ketoglutarate maintains the pluripotency of embryonic stem cells. Nature 2015, 518, 413–416. [Google Scholar] [CrossRef] [PubMed]
- Van der Knaap, J.A.; Verrijzer, C.P. Undercover: Gene control by metabolites and metabolic enzymes. Genes Dev. 2016, 30, 2345–2369. [Google Scholar] [CrossRef] [PubMed]
- Pan, M.; Reid, M.A.; Lowman, X.H.; Kulkarni, R.P.; Tran, T.Q.; Liu, X.; Yang, Y.; Hernandez-Davies, J.E.; Rosales, K.K.; Li, H.; et al. Regional glutamine deficiency in tumors promotes dedifferentiation through inhibition of histone demethylation. Nat. Cell Biol. 2016, 18, 1090–1101. [Google Scholar] [CrossRef] [PubMed]
- Calvert, A.E.; Chalastanis, A.; Wu, Y.; Hurley, L.A.; Kouri, F.M.; Bi, Y.; Kachman, M.; May, J.L.; Bartom, E.; Hua, Y.; et al. Cancer-associated IDH1 promotes growth and resistance to targeted therapies in the absence of mutation. Cell Rep. 2017, 19, 1858–1873. [Google Scholar] [CrossRef]
- Schuettengruber, B.; Bourbon, H.M.; Di Croce, L.; Cavalli, G. Genome regulation by Polycomb and Trithorax: 70 years and counting. Cell 2017, 171, 34–57. [Google Scholar] [CrossRef]
- Hwang, I.Y.; Kwak, S.; Lee, S.; Kim, H.; Lee, S.E.; Kim, J.H.; Kim, Y.A.; Jeon, Y.K.; Chung, D.H.; Jin, X.; et al. Psat1-dependent fluctuations in α-ketoglutarate affect the timing of ESC differentiation. Cell Metab. 2016, 24, 494–501. [Google Scholar] [CrossRef]
- Nagaoka, K.; Hino, S.; Sakamoto, A.; Anan, K.; Takase, R.; Umehara, T.; Yokoyama, S.; Sasaki, Y.; Nakao, M. Lysine-specific demethylase 2 suppresses lipid influx and metabolism in hepatic cells. Mol. Cell Biol. 2015, 35, 1068–1080. [Google Scholar] [CrossRef]
- Yang, S.J.; Park, Y.S.; Cho, J.H.; Moon, B.; An, H.J.; Lee, J.Y.; Xie, Z.; Wang, Y.; Pocalyko, D.; Lee, D.C.; et al. Regulation of hypoxia responses by flavin adenine dinucleotide-dependent modulation of HIF-1α protein stability. EMBO J. 2017, 36, 1011–1028. [Google Scholar] [CrossRef] [PubMed]
- Wojcieszyńska, D.; Hupert-Kocurek, K.; Guzik, U. Flavin-dependent enzymes in cancer prevention. Int J. Mol. Sci. 2012, 13, 16751–16768. [Google Scholar] [CrossRef] [PubMed]
- Amente, S.; Lania, L.; Majello, B. The histone LSD1 demethylase in stemness and cancer transcription programs. Biochim. Biophys Acta 2013, 1829, 981–986. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Collins, R.R.J.; Patel, K.; Putnam, W.C.; Kapur, P.; Rakheja, D. Oncometabolites: A new paradigm for oncology, metabolism, and the clinical laboratory. Clin. Chem. 2017, 63, 1812–1820. [Google Scholar] [CrossRef] [PubMed]
- Sciacovelli, M.; Frezza, C. Oncometabolites: Unconventional triggers of oncogenic signal. Free Radic. Biol. Med. 2016, 100, 175–181. [Google Scholar] [CrossRef] [PubMed]
- Skinner, R.; Trujillo, A.; Ma, X.; Beierle, E.A. Ketone bodies inhibit the viability of human neuroblastoma cells. J. Pediatr. Surg. 2009, 44, 212–216. [Google Scholar] [CrossRef] [PubMed]
- Shukla, S.K.; Gebregiworgis, T.; Purohit, V.; Chaika, N.V.; Gunda, V.; Radhakrishnan, P.; Mehla, K.; Pipinos, I.I.; Powers, R.; Yu, F.; et al. Metabolic reprogramming induced by ketone bodies diminishes pancreatic cancer cachexia. Cancer Metab. 2014. [Google Scholar] [CrossRef]
- Bonuccelli, G.; Tsirigos, A.; Whitaker-Menezes, D.; Pavlides, S.; Pestell, R.G.; Chiavarina, B.; Frank, P.G.; Flomenberg, N.; Howell, A.; Martinez-Outschoorn, U.E.; et al. Ketones and lactate ‘fuel’ tumor growth and metastasis: Evidence that epithelial cancer cells use oxidative mitochondrial metabolism. Cell Cycle 2010, 9, 3506–3514. [Google Scholar] [CrossRef]
- Martinez-Outschoorn, U.E.; Lin, Z.; Whitaker-Menezes, D.; Howell, A.; Sotqia, F.; Lisanti, M.P. Ketone body utilization drives tumor growth and metastasis. Cell Cycle 2012, 11, 3964–3971. [Google Scholar] [CrossRef] [Green Version]
- Rodrigues, L.M.; Uribe-Lewis, S.; Madhu, B.; Honess, D.J.; Stubbs, M.; Griffiths, J.R. The action of β-hydroxybutyrate on the growth, metabolism and global histone H3 acetylation of spontaneous mouse mammary tumours: Evidence of a β-hydroxybutyrate paradox. Cancer Metab. 2017. [Google Scholar] [CrossRef]
- Menendez, J.A.; Corominas-Faja, B.; Cujàs, E.; García, M.G.; Fernández-Arroyo, S.; Fernández, A.F.; Joven, J.; Fraga, M.F.; Alarcón, T. Oncometabolic nuclear reprogramming of cancer stemness. Stem Cell Rep. 2016, 6, 273–283. [Google Scholar] [CrossRef] [PubMed]
- Dando, I.; Pozza, E.D.; Ambrosini, G.; Torrens-Mas, M.; Butera, G.; Mullappilly, N.; Pacchiana, R.; Palmieri, M.; Donadelli, M. Oncometabolites in cancer aggressiveness and tumour repopulation. Biol Rev. Camb. Philos. Soc. 2019. [Google Scholar] [CrossRef] [PubMed]
- Condelli, V.; Crispo, F.; Pietrafesa, M.; Lettini, G.; Matassa, D.S.; Esposito, F.; Landriscina, M.; Maddalena, F. HSP90 molecular chaperone, metabolic rewiring and epigenetics: Impact on tumor progression and perspective for anticancer therapy. Cells 2019. [Google Scholar] [CrossRef] [PubMed]
- Sciacovelli, M.; Guzzo, G.; Morello, V.; Frezza, C.; Zheng, L.; Nannini, N.; Calabrese, F.; Laudiero, G.; Esposito, F.; Landriscina, M.; et al. The mitochondrial chaperone TRAP1 promotes neoplastic growth by inhibiting succinate dehydrogenase. Cell Metab. 2013, 17, 988–999. [Google Scholar] [CrossRef] [PubMed]
- Lettini, G.; Maddalena, F.; Sisinni, L.; Condelli, V.; Matassa, D.S.; Costi, M.P.; Simoni, D.; Esposito, F.; Landriscina, M. Targets TRAP1: A viable therapeutic target for future cancer treatments? Expert Opin. Ther. Targets 2017, 21, 805–815. [Google Scholar] [CrossRef] [PubMed]
- Matassa, D.S.; Agliarulo, I.; Avolio, R.; Landriscina, M.; Esposito, F. TRAP1 regulation of cancer metabolism: Dual role as oncogene or tumor suppressor. Genes 2018. [CrossRef] [PubMed]
- Sudarshan, S.; Shanmugasundaram, K.; Naylor, S.L.; Lin, S.; Livi, C.B.; O’Neill, C.F.; Parekh, D.J.; Yeh, I.T.; Sun, L.Z.; Block, K. Reduced expression of fumarate hydratase in clear cell renal cancer mediates HIF-2α accumulation and promotes migration and invasion. PLoS ONE 2011. [Google Scholar] [CrossRef] [PubMed]
- Sciacovelli, M.; Gonçalves, E.; Johnson, T.I.; Zecchini, V.R.; Henriques da Costa, A.S.; Gaude, E.; Drubbel, A.V.; Theobald, S.J.; Abbo, S.; Tran, M.; et al. Fumarate is an epigenetic modifier that elicits epithelial-to- mesenchymal transition. Nature 2016, 537, 544–547. [Google Scholar] [CrossRef] [PubMed]
- Intlekofer, A.M.; Dematteo, R.G.; Venneti, S.; Finley, L.W.S.; Lu, C.; Judkins, A.R.; Rustenburg, A.S.; Grinaway, P.B.; Chodera, J.D.; Cross, J.R.; et al. Hypoxia induces production of L-2-hydroxyglutarate. Cell Metab. 2015, 22, 304–311. [Google Scholar] [CrossRef]
- Intlekofer, A.M.; Wang, B.; Liu, H.; Shah, H.; Carmona-Fontaine, C.; Rustenburg, A.S.; Salah, S.; Gunner, M.R.; Chodera, J.D.; Cross, J.R.; et al. L-2-hydroxyglutarate production arises from non-canonical enzyme function at acidic pH. Nat. Chem. Biol. 2017, 13, 494–500. [Google Scholar] [CrossRef] [PubMed]
- Katada, S.; Imhof, A.; Sassone-Corsi, P. Connecting threads: Epigenetics and metabolism. Cell 2012, 148, 24–28. [Google Scholar] [CrossRef] [PubMed]
- Nieborak, A.; Schneider, R. Metabolic intermediates–cellular messangers talking to chromatin modifiers. Mol. Metab. 2018, 14, 39–52. [Google Scholar] [CrossRef] [PubMed]
- Reytor, E.; Pérez-Miguelsanz, J.; Álvarez, L.; Pérez-Sala, D.; Pajares, M.A. Conformational signals in the C-terminal domain of methionine adenosyltransferase I/III determine its nucleocytoplasmic distribution. FASEB J. 2009, 23, 3347–3360. [Google Scholar] [CrossRef] [PubMed]
- Pajares, M.A.; Álvarez, L.; Pérez-Sala, D. How are mammalian methionine adenosyltransferases regulated in the liver? A focus on redox stress. FEBS Lett. 2013, 587, 1711–1716. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Katoh, Y.; Ikura, T.; Hoshikawa, Y.; Tashiro, S.; Ito, T.; Ohta, M.; Kera, Y.; Noda, T.; Igarashi, K. Methionine adenosyltransferase II serves as a transcriptional corepressor of Maf oncoprotein. Mol. Cell. 2011, 5, 554–566. [Google Scholar] [CrossRef] [PubMed]
- Kera, Y.; Katoh, Y.; Ohta, M.; Matsumoto, M.; Takano-Yamamoto, T.; Igarashi, K. Methionine adenosyltransferase II-dependent histone H3K9 methylation at the COX-2 gene locus. J. Biol Chem. 2013, 288, 13592–13601. [Google Scholar] [CrossRef] [PubMed]
- Li, S.; Gogol, S.K.; Florens, L.; Washburn, M.P.; Jerry, L. Serine and SAM responsive complex SESAME regulates histone modification crosstalk by sensing cellular metabolism. Mol. Cell 2015, 60, 408–421. [Google Scholar] [CrossRef]
- Schug, Z.T.; Peck, B.; Jones, D.T.; Zhang, Q.; Grosskurth, S.; Alam, I.S.; Goodwin, L.M.; Smethurst, E.; Mason, S.; Blyth, K.; et al. Acetyl-CoA synthetase 2 promotes acetate utilization and maintains cancer cell growth under metabolic stress. Cancer Cell 2015, 27, 57–71. [Google Scholar] [CrossRef]
- Bulusu, V.; Tumanov, S.; Michalopoulou, E.; van den Broek, N.J.; MacKay, G.; Nixon, C.; Dhayade, S.; Schug, Z.T.; Vande Voorde, J.; Blyth, K.; et al. Acetate recapturing by nuclear acetyl-CoA synthetase 2 prevents loss of histone acetylation during oxygen and serum limitation. Cell Rep. 2017, 18, 647–658. [Google Scholar] [CrossRef]
- Takahashi, H.; McCaffery, M.; Irizarry, R.A.; Boeke, J.D. Nucleocytosolic acetyl-coenzyme A synthetase is required for histone acetylation and global transcription. Mol. Cell 2006, 23, 207–217. [Google Scholar] [CrossRef]
- Li, X.; Yu, W.; Qian, X.; Xia, Y.; Zheng, Y.; Lee, J.H.; Li, W.; Lyu, J.; Rao, G.; Zhang, X.; et al. Nucleus-translocated ACSS2 promotes gene transcription for lysosomal biogenesis and autophagy. Mol. Cell 2017, 66, 684–697. [Google Scholar] [CrossRef] [PubMed]
- Sivanand, S.; Rhoades, S.; Jiang, Q.; Lee, J.V.; Benci, J.; Zhang, J.; Yuan, S.; Viney, I.; Zhao, S.; Carrer, A.; et al. Nuclear acetyl-CoA production by ACLY promotes homologous recombination. Mol. Cell 2017, 67, 252–265. [Google Scholar] [CrossRef] [PubMed]
- Sutendra, G.; Kinnaird, A.; Dromparis, P.; Paulin, R.; Stenson, T.H.; Haromy, A.; Hashimoto, K.; Zhang, N.; Flaim, E.; Michelakis, E.D. A nuclear pyruvate dehydrogenase complex is important for the generation of acetyl-CoA and histone acetylation. Cell 2014, 158, 84–97. [Google Scholar] [CrossRef] [PubMed]
- Chen, J.; Guccini, I.; Mitri, D.D.; Brina, D.; Revandkar, A.; Sarti, M.; Pasquini, E.; Alajati, A.; Pinton, S.; Losa, M.; et al. Compartmentalized activities of the pyruvate dehydrogenase complex sustain lipogenesis in prostate cancer. Nat. Genet. 2018, 50, 219–228. [Google Scholar] [CrossRef] [PubMed]
- Madiraju, P.; Pande, S.V.; Prentki, M.; Murthy Madiraju, S.R. Mitochondrial acetylcarnitine provides acetyl groups for nuclear histone acetylation. Epigenetics 2009, 4, 399–403. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yang, W.; Lu, Z. Nuclear PKM2 regulates the Warburg effect. Cell Cycle 2013, 12, 3154–3158. [Google Scholar] [CrossRef] [PubMed]
- Desai, S.; Ding, M.; Wang, B.; Lu, Z.; Zhao, Q.; Shaw, K.; Yung, W.K.A.; Weinstein, J.N.; Tan, M.; Yao, J. Tissue-specific isoform switch and DNA hypomethylation of the pyruvate kinase PKM gene in human cancers. Oncotarget 2014, 5, 8202–8210. [Google Scholar] [CrossRef] [PubMed]
- 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, 118–122. [Google Scholar] [CrossRef] [PubMed]
- Yang, W.; Xia, Y.; Hawke, D.; Li, X.; Liang, J.; Xing, D.; Aldape, K.; Hunter, T.; Yung, W.K.A.; Lu, Z. PKM2 phosphorilates histone H3 and promotes gene transcription and tumorigenesis. Cell 2012, 17, 685–696. [Google Scholar] [CrossRef]
- Wang, H.J.; Hsieh, Y.J.; Cheng, W.C.; Lin, C.P.; Lin, Y.S.; Yang, S.F.; Chen, C.C.; Izumiya, Y.; Yu, J.S.; Kung, H.J.; et al. JMJD5 regulates PKM2 nuclear translocation and reprograms HIF-1α–mediated glucose metabolism. Proc. Natl. Acad. Sci. USA 2014, 111, 279–284. [Google Scholar] [CrossRef]
- Matsuda, S.; Adachi, J.; Ihara, M.; Tanuma, N.; Shima, H.; Kakizuka, A.; Ikura, M.; Ikura, T.; Matsuda, T. Nuclear pyruvate kinase M2 complex serves as a transcriptional coactivator of aryl hydrocarbon receptor. Nucleic Acids Res. 2016, 44, 636–647. [Google Scholar] [CrossRef] [PubMed]
- Minchenko, O.; Opentanova, I.; Minchenko, D.; Ogura, T.; Esumi, H. Hypoxia induces transcription of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-4 gene via hypoxia-inducible factor-1α activation. FEBS Lett. 2004, 576, 14–20. [Google Scholar] [CrossRef] [PubMed]
- Chesney, J.; Lane, A.N. Fructose-2,6-bisphosphate synthesis by required for the glycolytic response to hypoxia and tumor growth. Oncotarget 2014, 5, 6670–6686. [Google Scholar] [CrossRef] [PubMed]
- Dasgupta, S.; Rajapakshe, K.; Zhu, B.; Nikolai, B.C.; Yi, P.; Putluri, N.; Choi, J.M.; Jung, S.Y.; Coarfa, C.; Westbrook, T.F.; et al. Metabolic enzyme PFKFB4 activates transcriptional coactivator SRC-3 to drive breast cancer. Nature 2018, 556, 249–254. [Google Scholar] [CrossRef] [PubMed]
- Castonguay, Z.; Auger, C.; Thomas, S.C.; Chahma, M.; Appanna, V.D. Nuclear lactate dehydrogenase modulates histone modification in human hepatocytes. Biochem. Biophys Res. Commun. 2014, 454, 172–177. [Google Scholar] [CrossRef] [PubMed]
- Zhang, J.Y.; Zhang, F.; Hong, C.Q.; Giuliano, A.E.; Cui, X.J.; Zhou, G.J.; Zhang, G.J.; Cui, Y.K. Critical protein GAPDH and its regulatory mechanisms in cancer cells. Cancer Biol. Med. 2015, 12, 10–22. [Google Scholar] [CrossRef] [PubMed]
- Hara, M.R.; Agrawal, N.; Kim, S.F.; Cascio, M.B.; Fujimuro, M.; Ozeki, Y.; Takahashi, M.; Cheah, J.H.; Tankou, S.K.; Hester, L.D.; et al. S-nitrosylated GAPDH initiates apoptotic cell death by nuclear translocation following Siah1 binding. Nat. Cell Biol. 2005, 7, 665–674. [Google Scholar] [CrossRef] [PubMed]
- Kornberg, M.D.; Sen, N.; Hara, M.R.; Juluri, K.R.; Nguyen, J.V.K.; Snowman, A.M.; Law, L.; Hester, L.D.; Snyder, S.H. GAPDH mediates nitrosylation of nuclear proteins. Nat. Cell Biol. 2010, 12, 1094–1100. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Monaghan, R.M.; Whitmarsh, A.J. Mitochondrial proteins moonlighting in the nucleus. Trends Biochem Sci. 2015, 40, 728–735. [Google Scholar] [CrossRef]
- Jiang, Y.; Qian, X.; Shen, J.; Wang, Y.; Li, X.; Liu, R.; Xia, Y.; Chen, Q.; Peng, G.; Lin, S.Y.; et al. Local generation of fumarate promotes DNA repair through inhibition of histone H3 demethylation. Nat. Cell Biol. 2015, 17, 1158–1168. [Google Scholar] [CrossRef] [Green Version]
- May, J.L.; Kouri, F.M.; Hurley, L.A.; Liu, J.; Tommasini-Ghelfi, S.; Ji, Y.; Gao, P.; Calvert, A.E.; Lee, A.; Chandel, N.S.; et al. IDH3α regulates one-carbon metabolism in glioblastoma. Sci. Adv. 2019. [Google Scholar] [CrossRef] [PubMed]
- Agarwal, S.; Sharma, M.C.; Jha, P.; Pathak, P.; Suri, V.; Sarkar, C.; Chosdol, K.; Suri, A.; Kale, S.S.; Mahapatra, A.K.; et al. Comparative study of IDH1 mutations in gliomas by immunohistochemistry and DNA sequencing. Neuro. Oncol. 2013, 15, 718–726. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ying, W. NAD+/NADH and NADP+/NADPH in cellular functions and cell death: Regulation and biological consequences. Antioxid Redox Signal. 2008, 10, 179–206. [Google Scholar] [CrossRef] [PubMed]
- Goel, A.; Mathupala, S.P.; Pedersen, P.L. Glucose metabolism in cancer. Evidence that demethylation events play a role in activating type II hexokinase gene expression. J. Biol. Chem. 2003, 278, 15333–15340. [Google Scholar] [CrossRef] [PubMed]
- Lee, H.G.; Kim, H.; Son, T.; Jeong, Y.; Kim, S.U.; Dong, S.M.; Park, Y.N.; Lee, J.D.; Lee, J.M.; Park, J.H. Regulation of HK2 expression through alterations in CpG methylation of the HK2 promoter during progression of hepatocellular carcinoma. Oncotarget 2016, 7, 41798–41810. [Google Scholar] [CrossRef]
- Wolf, A.; Agnihotri, S.; Munoz, D.; Guha, A. Neurobiology of disease developmental profile and regulation of the glycolytic enzyme hexokinase 2 in normal brain and glioblastoma multiforme. Neurobiol. Dis. 2011, 44, 84–91. [Google Scholar] [CrossRef]
- Dong, Z.; Cui, H. Epigenetic modulation of metabolism in glioblastoma. Semin. Cancer Biol. 2018. [Google Scholar] [CrossRef]
- Chen, M.; Zhang, J.; Li, N.; Qian, Z.; Zhu, M.; Li, Q.; Zheng, J.; Wang, X.; Shi, G. Promoter hypermethylation mediated downregulation of FBP1 in human hepatocellular carcinoma and colon cancer. PLoS ONE 2011. [Google Scholar] [CrossRef]
- Dong, C.; Yuan, T.; Wu, Y.; Wang, Y.; Fan, T.W.M.; Miriyala, S.; Lin, Y.; Yao, J.; Shi, J.; Kang, T.; et al. Loss of FBP1 by Snail-mediated repression provides metabolic advantages in basal-like breast cancer. Cancer Cell 2013, 23, 316–331. [Google Scholar] [CrossRef]
- Li, L.; Li, W. Epithelial–mesenchymal transition in human cancer: Comprehensive reprogramming of metabolism, epigenetics, and differentiation. Pharmacol. Ther. 2015, 150, 33–46. [Google Scholar] [CrossRef]
- Pan, D.; Mao, C.; Wang, Y. Suppression of gluconeogenic gene expression by LSD1-mediated histone demethylation. PLoS ONE 2013. [Google Scholar] [CrossRef] [PubMed]
- Lopez-Serra, P.; Marcilla, M.; Villanueva, A.; Ramos-Fernandez, A.; Palau, A.; Leal, L.; Wahi, J.E.; Setien-Baranda, F.; Szczesna, K.; Moutinho, C.; et al. A DERL3-associated defect in the degradation of SLC2A1 mediates the Warburg effect. Nat. Commun. 2014. [Google Scholar] [CrossRef] [PubMed]
- Salvesen, H.B.; MacDonald, N.; Ryan, A.; Jacobs, I.J.; Lynch, E.D.; Akslen, L.A.; Das, S. PTEN methylation is associated with advanced stage and microsatellite instability in endometrail carcinoma. Int. J. Cancer 2001, 91, 22–26. [Google Scholar] [CrossRef]
- Kang, Y.; Lee, H.S.; Kim, W.H. Promoter methylation and silencing of PTEN in gastric carcinoma. Lab. Invest. 2002, 82, 285–291. [Google Scholar] [CrossRef]
- Soria, J.C.; Lee, H.Y.; Lee, J.I.; Wang, L.; Issa, J.P.; Kemp, B.L.; Liu, D.D.; Kurie, J.M.; Mao, L.; Khuri, F.R. Lack of PTEN expression in non-small cell lung cancer could be related to promoter methylation 1. Clin. Cancer Res. 2002, 8, 1178–1184. [Google Scholar]
- García, J.M.; Silva, J.; Peña, C.; Garcia, V.; Rodríguez, R.; Cruz, M.A.; Cantos, B.; Provencio, M.; España, P.; Bonilla, F. Promoter methylation of the PTEN gene is a common molecular change in breast cancer. Genes Chromosom. Cancer 2004, 41, 117–124. [Google Scholar] [CrossRef]
- Alvarez-Nuñez, F.; Bussaglia, E.; Mauricio, D.; Ybarra, J.; Vilar, M.; Lerma, E.; de Leiva, A.; Matias-Guiu, X. PTEN promoter methylation in sporadic thyroid carcinomas. Thyroid 2006, 16, 17–23. [Google Scholar] [CrossRef]
- Trojan, J.; Brieger, A.; Raedle, J.; Esteller, M.; Zeuzem, S. 5′-CpG island methylation of the LKB1/STK11 promoter and allelic loss at chromosome 19p13.3 in sporadic colorectal cancer. Gut 2000, 47, 272–276. [Google Scholar] [CrossRef]
- Esteller, M.; Avizienyte, E.; Corn, P.G.; Lothe, R.A.; Baylin, S.B.; Aaltonen, L.A.; Herman, J.G. Epigenetic inactivation of LKB1 in primary tumors associated with the Peutz-Jeghers syndrome. Oncogene 2000, 19, 164–168. [Google Scholar] [CrossRef] [Green Version]
- Herman, J.G.; Latif, F.; Weng, Y.; Lerman, M.I.; Zbar, B.; Liu, S.; Samid, D.; Duan, D.S.R.; Gnarra, J.R.; Linehan, W.M.; et al. Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma. Proc. Natl. Acad. Sci. USA 1994, 91, 9700–9704. [Google Scholar] [CrossRef]
- Schmitt, A.M.; Schmid, S.; Rudolph, T.; Anlauf, M.; Prinz, C.; Klöppel, G.; Moch, H.; Heitz, P.U.; Komminoth, P.; Perren, A. VHL inactivation is an important pathway for the development of malignant sporadic pancreatic endocrine tumors. Endocr. Relat. Cancer 2009, 16, 1219–1227. [Google Scholar] [CrossRef]
- Vanharanta, S.; Shu, W.; Brenet, F.; Hakimi, A.A.; Heguy, A.; Viale, A.; Reuter, V.E.; Hsieh, J.J.D.; Scandura, J.M.; Massagué, J. Epigenetic expansion of VHL-HIF signal output drives multiorgan metastasis in renal cancer. Nat. Med. 2013, 16, 50–56. [Google Scholar] [CrossRef] [PubMed]
- Place, T.L.; Fitzgerald, M.P.; Venkataraman, S.; Vorrink, S.U.; Case, A.J.; Teoh, M.L.; Domann, F.E. Aberrant promoter CpG methylation is a mechanism for impaired PHD3 expression in a diverse set of malignant cells. PLoS ONE 2011. [Google Scholar] [CrossRef] [PubMed]
- Rawluszko, A.; Bujnicka, K.B.; Horbacka, K.; Krokowicz, P.; Jagodziński, P.P. Expression and DNA methylation levels of prolyl hydroxylase PHD1, PHD2, PHD3 and asparaginyl hydroxylase FIH in colorectal cancer. BMC Cancer 2013. [Google Scholar] [CrossRef] [PubMed]
- Wan, W.; Peng, K.; Li, M.; Qin, L.; Tong, Z.; Yan, J.; Shen, B.; Yu, C. Histone demethylase JMJD1A promotes urinary bladder cancer progression by enhancing glycolysis through coactivation of hypoxia inducible factor 1α. Oncogene 2017, 36, 3868–3877. [Google Scholar] [CrossRef] [PubMed]
- Luo, L.; Chang, R.; Zhong, J.; Pandey, A.; Semenza, G.L. Histone demethylase JMJD2C is a coactivator for hypoxia-inducible factor 1 that is required for breast cancer progression. Proc. Natl. Acad. Sci. USA 2012. [Google Scholar] [CrossRef]
- Kozono, D.; Li, J.; Nitta, M.; Sampetrean, O.; Gonda, D.; Kushwaha, D.S.; Merzon, D.; Ramakrishnan, V.; Zhu, S.; Zhu, K.; et al. Dynamic epigenetic regulation of glioblastoma tumorigenicity through LSD1 modulation of MYC expression. Proc. Natl. Acad. Sci. USA 2015. [Google Scholar] [CrossRef] [PubMed]
- Chalkiadaki, A.; Guarente, L. The multifaceted functions of sirtuins in cancer. Nat. Rev. Cancer 2015, 15, 608–624. [Google Scholar] [CrossRef]
- Sebastián, C.; Zwaans, B.M.M.; Silberman, D.M.; Gymrek, M.; Goren, A.; Zhong, L.; Ram, O.; Truelove, J.; Guimaraes, A.R.; Toiber, D.; et al. The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism. Cell 2012, 151, 1185–1199. [Google Scholar] [CrossRef]
- Hallows, W.C.; Yu, W.; Denu, J.M. Regulation of glycolytic enzyme phosphoglycerate mutase-1. J. Biol. Chem. 2012, 287, 3850–3858. [Google Scholar] [CrossRef]
- Liu, P.Y.; Xu, N.; Malyukova, A.; Scarlett, C.J.; Sun, Y.T.; Zhang, X.D.; Ling, D.; Su, S.P.; Nelson, C.; Chang, D.K.; et al. The histone deacetylase SIRT2 stabilizes Myc oncoproteins. Cell Death Diff. 2013, 20, 503–514. [Google Scholar] [CrossRef] [PubMed]
- Matilainen, O.; Quirós, P.M.; Auwerx, J. Mitochondria and epigenetics–crosstalk in homeostasis and stress. Trends Cell Biol. 2017, 27, 453–463. [Google Scholar] [CrossRef] [PubMed]
- Rinaldi, G.; Rossi, M.; Fendt, S.M. Metabolic interactions in cancer: Cellular metabolism at the interface between the microenvironment, the cancer cell phenotype and the epigenetic landscape. Wiley Interdiscip. Rev. Syst. Biol. Med. 2018. [CrossRef] [PubMed]
- Domblides, C.; Lartigue, L.; Faustin, B. Control of the antitumor immune response by cancer metabolism. Cells 2019. [Google Scholar] [CrossRef] [PubMed]
- Wegiel, B.; Vuerich, M.; Daneshmandi, S.; Seth, P. Metabolic switch in the tumor microenvironment determines immune responses to anti-cancer therapy. Front. Oncol. 2018, 8, 284. [Google Scholar] [CrossRef] [PubMed]
- Colegio, O.R.; Chu, N.-Q.; Szabo, A.L.; Chu, T.; Rhebergen, A.M.; Jairam, V.; Cyrus, N.; Brokowski, C.E.; Eisenbarth, S.C.; Phillips, G.M.; et al. Functional polarization of tumour-associated macrophages by tumour-derived lactic acid. Nature 2014, 513, 559–563. [Google Scholar] [CrossRef] [PubMed]
- Ippolito, L.; Morandi, A.; Giannoni, E.; Chiarugi, P. Lactate: A metabolic driver in the tumour landscape. Trends Biochem. Sci. 2019, 44, 153–166. [Google Scholar] [CrossRef] [PubMed]
- Mu, X.; Shi, W.; Xu, Y.; Xu, C.; Zhao, T.; Geng, B.; Yang, J.; Pan, J.; Hu, S.; Zhang, C.; et al. Tumor-derived lactate induces M2 macrophage polarization via the activation of the ERK/STAT3 signaling pathway in breast cancer. Cell Cycle 2018, 17, 428–438. [Google Scholar] [CrossRef]
- Laoui, D.; Van Overmeire, E.; Di Conza, G.; Aldeni, C.; Keirsse, J.; Morias, Y.; Movahedi, K.; Houbracken, I.; Schouppe, E.; Elkrim, Y.; et al. Tumor hypoxia does not drive differentiation of tumor-associated macrophages but rather fine-tunes the M2-like macrophage population. Cancer Res. 2014, 74, 24–30. [Google Scholar] [CrossRef]
- Carmona-Fontaine, C.; Deforet, M.; Akkari, L.; Thompson, C.B.; Joyce, J.A.; Xavier, J.B. Metabolic origins of spatial organization in the tumor microenvironment. Proc. Natl. Acad. Sci. USA. 2017, 114, 2934–2939. [Google Scholar] [CrossRef] [Green Version]
- Seth, P.; Csizmadia, E.; Hedblom, A.; Vuerich, M.; Xie, H.; Li, M.; Longhi, M.S.; Wegiel, B. Deletion of Lactate Dehydrogenase-A in Myeloid Cells Triggers Antitumor Immunity. Cancer Res. 2017, 77, 3632–3643. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Renner, K.; Singer, K.; Koehl, G.E.; Geissler, E.K.; Peter, K.; Siska, P.J.; Kreutz, M. Metabolic hallmarks of tumor and immune cells in the tumor microenvironment. Front. Immunol. 2017. [Google Scholar] [CrossRef] [PubMed]
- Kouidhi, S.; Ben Ayed, F.; Benammar Elgaaied, A. Targeting Tumor Metabolism: A New Challenge to Improve Immunotherapy. Front. Immunol. 2018. [Google Scholar] [CrossRef] [PubMed]
- Mocellin, S.; Wang, E.; Marincola, F.M. Cytokines and immune response in the tumor microenvironment. J. Immunother. 1991, 24, 392–407. [Google Scholar] [CrossRef]
- Vega, M.A.; Corbí, A.L. Human macrophage activation: Too many functions and phenotypes for a single cell type. Inmunología 2006, 25, 248–272. [Google Scholar]
- Tekpli, X.; Landvik, N.E.; Anmarkud, K.H.; Skaug, V.; Haugen, A.; Zienolddiny, S. DNA methylation at promoter regions of interleukin 1B, interleukin 6, and interleukin 8 in non-small cell lung cancer. Cancer Immunol. Immunother. 2013, 62, 337–345. [Google Scholar] [CrossRef] [PubMed]
- Marks, D.L.; Olson, R.L.; Fernandez-Zapico, M.E. Epigenetic control of the tumor microenvironment. Epigenomics. 2016, 8, 1671–1687. [Google Scholar] [CrossRef] [Green Version]
- Latham, T.; Mackay, L.; Sproul, D.; Karim, M.; Culley, J.; Harrison, D.J.; Hayward, L.; Langridge-Smith, P.; Gilbert, N.; Ramsahoye, B.H. Lactate, a product of glycolytic metabolism, inhibits histone deacetylase activity and promotes changes in gene expression. Nucleic Acids Res. 2012, 40, 4794–4803. [Google Scholar] [CrossRef] [Green Version]
- Tran, T.Q.; Lowman, X.H.; Kong, M. Molecular pathways: Metabolic control of histone methylation and gene expression in cancer. Clin. Cancer Res. 2017, 23, 4004–4009. [Google Scholar] [CrossRef]
- Glazer, R.I.; Hartman, K.D.; Knode, M.C.; Richard, M.M.; Chiang, P.K.; Tseng, C.K.; Marquez, V.E. 3-Deazaneplanocin: A new and potent inhibitor of s-adenosylhomocysteine hydrolase and its effects on human promyelocytic leukemia cell line HL-60. Biochem Biophys Res. Commun. 1986, 135, 688–694. [Google Scholar] [CrossRef]
- Momparler, R.L.; Côté, S.; Momparler, L.F.; Idaghdour, Y. Epigenetic therapy of acute myeloid leukemia using 5-aza-2′-deoxycytidine (decitabine) in combination with inhibitors of histone methylation and deacetylation. Clin. Epigenetics. 2014. [CrossRef] [PubMed]
- Momparler, R.L.; Côté, S. Targeting of cancer stem cells by inhibitors of DNA and histone methylation. Expert Opin. Investig. Drugs. 2015, 24, 1031–1043. [Google Scholar] [CrossRef] [PubMed]
- Dhillon, S. Ivosidenib: First global approval. Drugs 2018, 78, 1509–1516. [Google Scholar] [CrossRef]
- Yen, K.; Travins, J.; Wang, F.; David, M.D.; Artin, E.; Straley, K.; Padyana, A.; Gross, S.; De La Barre, B.; Tobin, E.; et al. AG-221, a first-in-class therapy targeting acute myeloid leukemia harboring oncogenic idh2 mutations. Cancer Discov. 2017, 7, 478–493. [Google Scholar] [CrossRef] [PubMed]
- Liu, X.S.; Little, J.B.; Yuan, Z.M. Glycolytic metabolism influences global chromatin structure. Oncotarget 2015, 6, 4214–4225. [Google Scholar] [CrossRef] [PubMed]
- Moussaieff, A.; Rouleau, M.; Kitsberg, D.; Cohen, M.; Levy, G.; Barasch, D.; Nemirovski, A.; Shen-Orr, S.; Laevsky, I.; Amit, M.; et al. Glycolysis-mediated changes in acetyl-CoA and histone acetylation control the early differentiation of embryonic stem cells. Cell Metab. 2015, 21, 392–402. [Google Scholar] [CrossRef] [PubMed]
- Robinson, M.M.; McBryant, S.J.; Tsukamoto, T.; Rojas, C.; Ferraris, D.V.; Hamilton, S.K. Novel mechanism of inhibition of rat kidney-type glutaminase by bis-2-(5- phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide (BPTES). Biochem. J. 2007, 406, 407–414. [Google Scholar] [CrossRef] [PubMed]
- Simpson, N.E.; Tryndyak, V.P.; Pogribna, M.; Beland, F.A.; Pogribny, I.P. Modifying metabolically sensitive histone marks by inhibiting glutamine metabolism affects gene expression and alters cancer cell phenotype. Epigenetics 2012, 7, 1413–1420. [Google Scholar] [CrossRef] [Green Version]
- Elhammali, A.; Ippolito, J.E.; Collins, L.; Crowley, J.; Marasa, J.; Piwnica-Worms, D. A high-throughput fluorimetric assay for 2-hydroxyglutarate identifies zaprinast as a glutaminase inhibitor. Cancer Discov. 2014, 4, 828–839. [Google Scholar] [CrossRef]
- Ferrari, A.; Longo, R.; Silva, R.; Mitro, N.; Caruso, D.; De Fabiani, E.; Crestani, M. Epigenome modifiers and metabolic rewiring: New frontiers in therapeutics. Pharmacol. Ther. 2018, 193, 178–193. [Google Scholar] [CrossRef]
- Alcarraz-Vizán, G.; Boren, J.; Lee, W.P.; Cascante, M. Histone deacetylase inhibition results in a common metabolic profile associated with HT29 differentiation. Metabolomics 2010, 6, 229–237. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Borodovsky, A.; Salmasi, V.; Turcan, S.; Fabius, A.W.; Baia, G.S.; Eberhart, C.G.; Weingart, J.D.; Gallia, G.L.; Baylin, S.B.; Chan, T.A.; et al. 5-azacytidine reduces methylation, promotes differentiation and induces tumor regression in a patient-derived IDH1 mutant glioma xenograft. Oncotarget 2013, 4, 1737–1747. [Google Scholar] [CrossRef] [PubMed]
- Turcan, S.; Fabius, A.W.; Borodovsky, A.; Pedraza, A.; Brennan, C.; Huse, J.; Viale, A.; Riggins, G.J.; Chan, T.A. Efficient induction of differentiation and growth inhibition in IDH1 mutant glioma cells by the DNMT Inhibitor Decitabine. Oncotarget 2013, 4, 1729–1736. [Google Scholar] [CrossRef] [PubMed]
- Fouad, Y.A.; Aanei, C. Revisiting the hallmarks of cancer. Am. J. Cancer Res. 2017, 7, 1016–1036. [Google Scholar] [PubMed]
- Wardell, S.E.; Ilkayeva, O.R.; Wieman, H.L.; Frigo, D.E.; Rathmell, J.C.; Newgard, C.B.; McDonnell, D.P. Glucose metabolism as a target of histone. Mol. Endocrinol. 2009, 23, 388–401. [Google Scholar] [CrossRef] [PubMed]
- Amoêdo, N.D.; Rodrigues, M.F.; Pezzuto, P.; Galina, A.; da Costa, R.M.; de Almeida, F.C.; El-Bacha, T.; Rumjanek, F.D. Energy metabolism in H460 lung cancer cells: Effects of histone deacetylase inhibitors. PLoS ONE 2011. [Google Scholar] [CrossRef] [PubMed]
- Rodrigues, M.F.; Carvalho, É.; Pezzuto, P.; Rumjanek, F.D.; Amoêdo, N.D. Reciprocal modulation of histone deacetylase inhibitors sodium butyrate and trichostatin A on the energy metabolism of breast cancer cells. J. Cell Biochem. 2015, 116, 797–808. [Google Scholar] [CrossRef] [PubMed]
- Mahmood, N.; Cheishvili, D.; Arakelian, A.; Tanvir, I.; Khan, H.A.; Pépin, A.S.; Szyf, M.; Rabbani, S.A. Methyl donor S-adenosylmethionine (SAM) supplementation attenuates breast cancer growth, invasion, and metastasis in vivo; therapeutic and chemopreventive applications. Oncotarget 2018, 9, 5169–5183. [Google Scholar] [CrossRef]
- Li, L.; Paz, A.C.; Wilky, B.A.; Johnson, B.; Galoian, K.; Rosenberg, A.; Hu, G.; Tinoco, G.; Bodamer, O.; Trent, J.C. Treatment with a small molecule mutant IDH1 inhibitor suppresses tumorigenic activity and decreases production of the oncometabolite 2-hydroxyglutarate in human chondrosarcoma cells. PLoS ONE 2015. [Google Scholar] [CrossRef]
- Dalle, I.A.; DiNardo, C.D. The role of enasidenib in the treatment of mutant IDH2 acute myeloid leukemia. Ther. Adv. Hematol. 2018, 9, 163–173. [Google Scholar] [CrossRef]
- Miranda, T.B.; Cortez, C.C.; Yoo, C.B.; Liang, G.; Abe, M.; Kelly, T.K.; Marquez, V.E.; Jones, P.A. DZNep is a global histone methylation inhibitor that reactivates developmental genes not silenced by DNA methylation. Mol. Cancer Ther. 2009, 8, 1579–1588. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lin, S.H.; Liu, T.; Ming, X.; Tang, Z.; Fu, L.; Schmitt-Kopplin, P.; Kanawati, B.; Guan, X.Y.; Cai, Z. Regulatory role of hexosamine biosynthetic pathway on hepatic cancer stem cell marker CD133 under low glucose conditions. Sci. Rep. 2016. [CrossRef] [PubMed]
- Fiskus, W.; Wang, Y.; Sreekumar, A.; Buckley, K.M.; Shi, H.; Jillella, A.; Ustun, C.; Rao, R.; Fernandez, P.; Chen, J.; et al. Combined epigenetic therapy with the histone methyltransferase EZH2 inhibitor 3-deazaneplanocin A and the histone deacetylase inhibitor panobinostat against human AML cells. Blood 2009, 114, 2733–2744. [Google Scholar] [CrossRef] [PubMed]
- Egler, V.; Korur, S.; Failly, M.; Boulay, J.; Imber, R.; Lino, M.M.; Merlo, A. Histone deacetylase inhibition and blockade of the glycolytic pathway synergistically induce glioblastoma cell death. Cancer Ther. Preclin. 2008, 14, 3132–3141. [Google Scholar] [CrossRef] [PubMed]
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Crispo, F.; Condelli, V.; Lepore, S.; Notarangelo, T.; Sgambato, A.; Esposito, F.; Maddalena, F.; Landriscina, M. Metabolic Dysregulations and Epigenetics: A Bidirectional Interplay that Drives Tumor Progression. Cells 2019, 8, 798. https://0-doi-org.brum.beds.ac.uk/10.3390/cells8080798
Crispo F, Condelli V, Lepore S, Notarangelo T, Sgambato A, Esposito F, Maddalena F, Landriscina M. Metabolic Dysregulations and Epigenetics: A Bidirectional Interplay that Drives Tumor Progression. Cells. 2019; 8(8):798. https://0-doi-org.brum.beds.ac.uk/10.3390/cells8080798
Chicago/Turabian StyleCrispo, Fabiana, Valentina Condelli, Silvia Lepore, Tiziana Notarangelo, Alessandro Sgambato, Franca Esposito, Francesca Maddalena, and Matteo Landriscina. 2019. "Metabolic Dysregulations and Epigenetics: A Bidirectional Interplay that Drives Tumor Progression" Cells 8, no. 8: 798. https://0-doi-org.brum.beds.ac.uk/10.3390/cells8080798