Lactate promotes glutamine uptake and metabolism in oxidative cancer cells

References

• Porporato PE, Dhup S, Dadhich RK, Copetti T, Sonveaux P. Anticancer targets in the glycolytic metabolism of tumors: a comprehensive review. Front Pharmacol 2011; 2:49; PMID:21904528; http://dx.doi.org/10.3389/fphar.2011.00049
   PubMed Web of Science ®Google Scholar
• Ward PS, Thompson CB. Metabolic reprogramming: a cancer hallmark even warburg did not anticipate. Cancer Cell 2012; 21:297-308; PMID:22439925; http://dx.doi.org/10.1016/j.ccr.2012.02.014
   PubMed Web of Science ®Google Scholar
• Wu R, Racker E. Regulatory mechanisms in carbohydrate metabolism. IV. Pasteur effect and Crabtree effect in ascites tumor cells. J Biol Chem 1959; 234:1036–41; PMID:13654314
   PubMed Web of Science ®Google Scholar
• Kolobova E, Tuganova A, Boulatnikov I, Popov KM. Regulation of pyruvate dehydrogenase activity through phosphorylation at multiple sites. Biochem J 2001; 358:69–77; PMID:11485553; http://dx.doi.org/10.1042/bj3580069
   PubMed Web of Science ®Google Scholar
• Papandreou I, Cairns RA, Fontana L, Lim AL, Denko NC. HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. Cell Metab 2006; 3:187–97; PMID:16517406; http://dx.doi.org/10.1016/j.cmet.2006.01.012
   PubMed Web of Science ®Google Scholar
• Dewhirst MW, Cao Y, Moeller B. Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response. Nat Rev Cancer 2008; 8:425–37; PMID:18500244; http://dx.doi.org/10.1038/nrc2397
   PubMed Web of Science ®Google Scholar
• Sowter HM, Raval RR, Moore JW, Ratcliffe PJ, Harris AL. Predominant role of hypoxia-inducible transcription factor (Hif)-1alpha versus Hif-2alpha in regulation of the transcriptional response to hypoxia. Cancer Res 2003; 63:6130–4; PMID:14559790
   PubMed Web of Science ®Google Scholar
• Bustamante E, Pedersen PL. High aerobic glycolysis of rat hepatoma cells in culture: role of mitochondrial hexokinase. Proc Natl Acad Sci U S A 1977; 74:3735–9; PMID:198801; http://dx.doi.org/10.1073/pnas.74.9.3735
   PubMed Web of Science ®Google Scholar
• Mathupala SP, Rempel A, Pedersen PL. Glucose catabolism in cancer cells: identification and characterization of a marked activation response of the type II hexokinase gene to hypoxic conditions. J Biol Chem 2001; 276:43407–12; PMID:11557773; http://dx.doi.org/10.1074/jbc.M108181200
   PubMed Web of Science ®Google Scholar
• Mazurek S, Boschek CB, Hugo F, Eigenbrodt E. Pyruvate kinase type M2 and its role in tumor growth and spreading. Semin Cancer Biol 2005; 15:300–8; PMID:15908230; http://dx.doi.org/10.1016/j.semcancer.2005.04.009
   PubMed Web of Science ®Google Scholar
• 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; 452:230–3; PMID:18337823; http://dx.doi.org/10.1038/nature06734
   PubMed Web of Science ®Google Scholar
• Mazurek S. Pyruvate kinase type M2: A key regulator of the metabolic budget system in tumor cells. Int J Biochem Cell Biol 2011; 43:969–80; PMID:20156581; http://dx.doi.org/10.1016/j.biocel.2010.02.005
   PubMed Web of Science ®Google Scholar
• Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 2009; 324:1029–33; PMID:19460998; http://dx.doi.org/10.1126/science.1160809
   PubMed Web of Science ®Google Scholar
• Hensley CT, Wasti AT, DeBerardinis RJ. Glutamine and cancer: cell biology, physiology, and clinical opportunities. J Clin Invest 2013; 123:3678–84; PMID:23999442; http://dx.doi.org/10.1172/JCI69600
   PubMed Web of Science ®Google Scholar
• Mullen AR, Wheaton WW, Jin ES, Chen PH, Sullivan LB, Cheng T, Yang Y, Linehan WM, Chandel NS, DeBerardinis RJ. Reductive carboxylation supports growth in tumour cells with defective mitochondria. Nature 2012; 481:385–8
   PubMed Web of Science ®Google Scholar
• 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; 463:364–8; PMID:20010808; http://dx.doi.org/10.1038/nature08697
   PubMed Web of Science ®Google Scholar
• Wise DR, DeBerardinis RJ, Mancuso A, Sayed N, Zhang XY, Pfeiffer HK, Nissim I, Daikhin E, Yudkoff M, McMahon SB, Thompson CB. Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction. Proc Natl Acad Sci U S A 2008; 105:18782–7; PMID:19033189; http://dx.doi.org/10.1073/pnas.0810199105
   PubMed Web of Science ®Google Scholar
• Gao P, Tchernyshyov I, Chang TC, Lee YS, Kita K, Ochi T, Zeller KI, De Marzo AM, Van Eyk JE, Mendell JT, Dang CV. c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism. Nature 2009; 458:762–5; PMID:19219026; http://dx.doi.org/10.1038/nature07823
   PubMed Web of Science ®Google Scholar
• DeBerardinis RJ, Mancuso A, Daikhin E, Nissim I, Yudkoff M, Wehrli S, Thompson CB. Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc Natl Acad Sci U S A 2007; 104:19345–50; PMID:18032601; http://dx.doi.org/10.1073/pnas.0709747104
   PubMed Web of Science ®Google Scholar
• Sonveaux P, Vegran F, Schroeder T, Wergin MC, Verrax J, Rabbani ZN, De Saedeleer CJ, Kennedy KM, Diepart C, Jordan BF, et al. Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice. J Clin Invest 2008; 118:3930–42; PMID:19033663
   PubMed Web of Science ®Google Scholar
• Van Hee VF, Perez-Escuredo J, Cacace A, Copetti T, Sonveaux P. Lactate does not activate NF-kB in oxidative tumor cells. Front Pharmacol 2015; 6:228; PMID:26528183; http://dx.doi.org/10.3389/fphar.2015.00228
   PubMed Web of Science ®Google Scholar
• Bonuccelli G, Tsirigos A, Whitaker-Menezes D, Pavlides S, Pestell RG, Chiavarina B, Frank PG, Flomenberg N, Howell A, Martinez-Outschoorn UE, et al. Ketones and lactate "fuel" tumor growth and metastasis: Evidence that epithelial cancer cells use oxidative mitochondrial metabolism. Cell Cycle 2010; 9:3506–14; PMID:20818174; http://dx.doi.org/10.4161/cc.9.17.12731
   PubMed Web of Science ®Google Scholar
• Lu H, Forbes RA, Verma A. Hypoxia-inducible factor 1 activation by aerobic glycolysis implicates the Warburg effect in carcinogenesis. J Biol Chem 2002; 277:23111–5; PMID:11943784; http://dx.doi.org/10.1074/jbc.M202487200
   PubMed Web of Science ®Google Scholar
• Lu H, Dalgard CL, Mohyeldin A, McFate T, Tait AS, Verma A. Reversible inactivation of HIF-1 prolyl hydroxylases allows cell metabolism to control basal HIF-1. J Biol Chem 2005; 280:41928–39; PMID:16223732; http://dx.doi.org/10.1074/jbc.M508718200
   PubMed Web of Science ®Google Scholar
• De Saedeleer CJ, Copetti T, Porporato PE, Verrax J, Feron O, Sonveaux P. Lactate activates HIF-1 in oxidative but not in Warburg-phenotype human tumor cells. PLoS ONE 2012; 7:e46571; PMID:23082126; http://dx.doi.org/10.1371/journal.pone.0046571
   PubMed Web of Science ®Google Scholar
• DeBerardinis RJ, Cheng T. Q's next: the diverse functions of glutamine in metabolism, cell biology and cancer. Oncogene 2010; 29:313–24; PMID:19881548; http://dx.doi.org/10.1038/onc.2009.358
   PubMed Web of Science ®Google Scholar
• Leite TC, Coelho RG, Da Silva D, Coelho WS, Marinho-Carvalho MM, Sola-Penna M. Lactate downregulates the glycolytic enzymes hexokinase and phosphofructokinase in diverse tissues from mice. FEBS Lett 2011; 585:92–8; PMID:21074528; http://dx.doi.org/10.1016/j.febslet.2010.11.009
   PubMed Web of Science ®Google Scholar
• Halestrap AP, Wilson MC. The monocarboxylate transporter family–role and regulation. IUBMB Life 2012; 64:109–19; PMID:22162139; http://dx.doi.org/10.1002/iub.572
   PubMed Web of Science ®Google Scholar
• Invernizzi F, D'Amato I, Jensen PB, Ravaglia S, Zeviani M, Tiranti V. Microscale oxygraphy reveals OXPHOS impairment in MRC mutant cells. Mitochondrion 2012; 12:328–35; PMID:22310368; http://dx.doi.org/10.1016/j.mito.2012.01.001
   PubMed Web of Science ®Google Scholar
• Gatenby RA, Gillies RJ. Why do cancers have high aerobic glycolysis?. Nat Rev Cancer 2004; 4:891–9; PMID:15516961; http://dx.doi.org/10.1038/nrc1478
   PubMed Web of Science ®Google Scholar
• De Saedeleer CJ, Porporato PE, Copetti T, Perez-Escuredo J, Payen VL, Brisson L, Feron O, Sonveaux P. Glucose deprivation increases monocarboxylate transporter 1 (MCT1) expression and MCT1-dependent tumor cell migration. Oncogene 2014; 33:4060–8; PMID:24166504; http://dx.doi.org/10.1038/onc.2013.454
   PubMed Web of Science ®Google Scholar
• Katt WP, Cerione RA. Glutaminase regulation in cancer cells: a druggable chain of events. Drug Discov Today 2014; 19:450–7; PMID:24140288; http://dx.doi.org/10.1016/j.drudis.2013.10.008
   PubMed Web of Science ®Google Scholar
• Pappalardi MB, McNulty DE, Martin JD, Fisher KE, Jiang Y, Burns MC, Zhao H, Ho T, Sweitzer S, Schwartz B, et al. Biochemical characterization of human HIF hydroxylases using HIF protein substrates that contain all three hydroxylation sites. Biochem J 2011; 436:363–9; PMID:21410436; http://dx.doi.org/10.1042/BJ20101201
   PubMed Web of Science ®Google Scholar
• Loboda A, Jozkowicz A, Dulak J. HIF-1 and HIF-2 transcription factors–similar but not identical. Mol Cells 2010; 29:435–42; PMID:20396958; http://dx.doi.org/10.1007/s10059-010-0067-2
   PubMed Web of Science ®Google Scholar
• Corn PG, Ricci MS, Scata KA, Arsham AM, Simon MC, Dicker DT, El-Deiry WS. Mxi1 is induced by hypoxia in a HIF-1-dependent manner and protects cells from c-Myc-induced apoptosis. Cancer Biol Ther 2005; 4:1285–94; PMID:16319523; http://dx.doi.org/10.4161/cbt.4.11.2299
   PubMed Web of Science ®Google Scholar
• Zhang H, Gao P, Fukuda R, Kumar G, Krishnamachary B, Zeller KI, Dang CV, Semenza GL. HIF-1 inhibits mitochondrial biogenesis and cellular respiration in VHL-deficient renal cell carcinoma by repression of C-MYC activity. Cancer Cell 2007; 11:407–20; PMID:17482131; http://dx.doi.org/10.1016/j.ccr.2007.04.001
   PubMed Web of Science ®Google Scholar
• Walenta S, Schroeder T, Mueller-Klieser W. Lactate in solid malignant tumors: potential basis of a metabolic classification in clinical oncology. Curr Med Chem 2004; 11:2195–204; PMID:15279558; http://dx.doi.org/10.2174/0929867043364711
   PubMed Web of Science ®Google Scholar
• Walenta S, Mueller-Klieser WF. Lactate: mirror and motor of tumor malignancy. Semin Radiat Oncol 2004; 14:267–74; PMID:15254870; http://dx.doi.org/10.1016/j.semradonc.2004.04.004
   PubMed Web of Science ®Google Scholar
• Kennedy KM, Scarbrough PM, Ribeiro A, Richardson R, Yuan H, Sonveaux P, Landon CD, Chi JT, Pizzo S, Schroeder T, Dewhirst MW. Catabolism of exogenous lactate reveals it as a legitimate metabolic substrate in breast cancer. PLoS ONE 2013; 8:e75154; PMID:24069390; http://dx.doi.org/10.1371/journal.pone.0075154
   PubMed Web of Science ®Google Scholar
• Busk M, Walenta S, Mueller-Klieser W, Steiniche T, Jakobsen S, Horsman MR, Overgaard J. Inhibition of tumor lactate oxidation: Consequences for the tumor microenvironment. Radiother Oncol 2011; 99:404–11; PMID:21704401; http://dx.doi.org/10.1016/j.radonc.2011.05.053
   PubMed Web of Science ®Google Scholar
• Nakajima EC, Van HB. Metabolic symbiosis in cancer: refocusing the Warburg lens. Mol Carcinog 2013; 52:329–37; PMID:22228080; http://dx.doi.org/10.1002/mc.21863
   PubMed Web of Science ®Google Scholar
• Guillaumond F, Leca J, Olivares O, Lavaut MN, Vidal N, Berthezene P, Dusetti NJ, Loncle C, Calvo E, Turrini O, et al. Strengthened glycolysis under hypoxia supports tumor symbiosis and hexosamine biosynthesis in pancreatic adenocarcinoma. Proc Natl Acad Sci U S A 2013; 110:3919–24; PMID:23407165; http://dx.doi.org/10.1073/pnas.1219555110
   PubMed Web of Science ®Google Scholar
• McGillen JB, Kelly CJ, Martinez-Gonzalez A, Martin NK, Gaffney EA, Maini PK, Perez-Garcia VM. Glucose-lactate metabolic cooperation in cancer: Insights from a spatial mathematical model and implications for targeted therapy. J Theor Biol 2014; 361:190–203; PMID:25264268; http://dx.doi.org/10.1016/j.jtbi.2014.09.018
   PubMed Web of Science ®Google Scholar
• Kianercy A, Veltri R, Pienta KJ. Critical transitions in a game theoretic model of tumour metabolism. Interface Focus 2014; 4:20140014; PMID:25097747; http://dx.doi.org/10.1098/rsfs.2014.0014
   PubMed Web of Science ®Google Scholar
• Sonveaux P, Copetti T, De Saedeleer CJ, Vegran F, Verrax J, Kennedy KM, Moon EJ, Dhup S, Danhier P, Frerart F, et al. Targeting the lactate transporter MCT1 in endothelial cells inhibits lactate-induced HIF-1 activation and tumor angiogenesis. PLoS ONE 2012; 7:e33418; PMID:22428047; http://dx.doi.org/10.1371/journal.pone.0033418
   PubMed Web of Science ®Google Scholar
• Vegran F, Boidot R, Michiels C, Sonveaux P, Feron O. Lactate influx through the endothelial cell monocarboxylate transporter MCT1 supports an NF-kappaB/IL-8 pathway that drives tumor angiogenesis. Cancer Res 2011; 71:2550–60; PMID:21300765; http://dx.doi.org/10.1158/0008-5472.CAN-10-2828
   PubMed Web of Science ®Google Scholar
• Roland CL, Arumugam T, Deng D, Liu SH, Philip B, Gomez S, Burns WR, Ramachandran V, Wang H, Cruz-Monserrate Z, et al. Cell surface lactate receptor GPR81 is crucial for cancer cell survival. Cancer Res 2014; 74:5301–10; PMID:24928781; http://dx.doi.org/10.1158/0008-5472.CAN-14-0319
   PubMed Web of Science ®Google Scholar
• Appelhoff RJ, Tian YM, Raval RR, Turley H, Harris AL, Pugh CW, Ratcliffe PJ, Gleadle JM. Differential function of the prolyl hydroxylases PHD1, PHD2, and PHD3 in the regulation of hypoxia-inducible factor. J Biol Chem 2004; 279:38458–65; PMID:15247232; http://dx.doi.org/10.1074/jbc.M406026200
   PubMed Web of Science ®Google Scholar
• DeBoer LW, Bekx PA, Han L, Steinke L. Pyruvate enhances recovery of rat hearts after ischemia and reperfusion by preventing free radical generation. Am J Physiol 1993; 265:H1571–6; PMID:8238569
   PubMed Web of Science ®Google Scholar
• Russell RR, III, Taegtmeyer H. Pyruvate carboxylation prevents the decline in contractile function of rat hearts oxidizing acetoacetate. Am J Physiol 1991; 261:H1756–62; PMID:1750532
   PubMed Web of Science ®Google Scholar
• Corbet C, Draoui N, Polet F, Pinto A, Drozak X, Riant O, Feron O. The SIRT1/HIF2alpha Axis Drives Reductive Glutamine Metabolism under Chronic Acidosis and Alters Tumor Response to Therapy. Cancer Res 2014; 74:5507–19; PMID:25085245; http://dx.doi.org/10.1158/0008-5472.CAN-14-0705
   PubMed Web of Science ®Google Scholar
• Reitzer LJ, Wice BM, Kennell D. Evidence that glutamine, not sugar, is the major energy source for cultured HeLa cells. J Biol Chem 1979; 254:2669–76; PMID:429309
   PubMed Web of Science ®Google Scholar
• Cardaci S, Rizza S, Filomeni G, Bernardini R, Bertocchi F, Mattei M, Paci M, Rotilio G, Ciriolo MR. Glutamine deprivation enhances antitumor activity of 3-bromopyruvate through the stabilization of monocarboxylate transporter-1. Cancer Res 2012; 72:4526–36; PMID:22773663; http://dx.doi.org/10.1158/0008-5472.CAN-12-1741
   PubMed Web of Science ®Google Scholar
• Doherty JR, Yang C, Scott KE, Cameron MD, Fallahi M, Li W, Hall MA, Amelio AL, Mishra JK, Li F, et al. Blocking lactate export by inhibiting the Myc target MCT1 Disables glycolysis and glutathione synthesis. Cancer Res 2014; 74:908–20; PMID:24285728; http://dx.doi.org/10.1158/0008-5472.CAN-13-2034
   PubMed Web of Science ®Google Scholar
• Soderberg O, Gullberg M, Jarvius M, Ridderstrale K, Leuchowius KJ, Jarvius J, Wester K, Hydbring P, Bahram F, Larsson LG, et al. Direct observation of individual endogenous protein complexes in situ by proximity ligation. Nat Methods 2006; 3:995–1000; PMID:17072308; http://dx.doi.org/10.1038/nmeth947
   PubMed Web of Science ®Google Scholar