Cancer Cell Metabolism: One Hallmark, Many Faces

Greaves, 2012, Clonal evolution in cancer, Nature, 481, 306, 10.1038/nature10762

Siegel, 2012, Cancer statistics, 2012, CA Cancer J Clin, 62, 10, 10.3322/caac.20138

Kelloff, 2012, Cancer biomarkers: selecting the right drug for the right patient, Nat Rev Drug Discov, 11, 1, 10.1038/nrd3651

Wong, 2011, Unraveling the genetics of cancer: genome sequencing and beyond, Annu Rev Genomics Hum Genet, 12, 407, 10.1146/annurev-genom-082509-141532

Gerlinger, 2012,  Intratumor heterogeneity and branched evolution revealed by multiregion sequencing, N Engl J Med, 366, 883, 10.1056/NEJMoa1113205

Yap, 2012, Intratumor heterogeneity: seeing the wood for the trees, Sci Transl Med, 4, 1, 10.1126/scitranslmed.3003854

Marusyk, 2012, Intra-tumour heterogeneity: a looking glass for cancer?, Nat Rev Cancer, 12, 323, 10.1038/nrc3261

Hanahan, 2011, Hallmarks of Cancer: the next generation, Cell, 144, 646, 10.1016/j.cell.2011.02.013

Warburg, 1927, The metabolism of tumors in the body, J Gen Physiol, 8, 519, 10.1085/jgp.8.6.519

Vander Heiden, 2009, Understanding the Warburg effect: the metabolic requirements of cell proliferation, Science, 324, 1029, 10.1126/science.1160809

Hsu, 2008, Cancer cell metabolism: Warburg and beyond, Cell, 134, 703, 10.1016/j.cell.2008.08.021

Ward, 2012, Metabolic reprogramming: a cancer hallmark even Warburg did not anticipate, Cancer Cell, 21, 297, 10.1016/j.ccr.2012.02.014

Warburg, 1956, On the origin of cancer cells, Science, 123, 309, 10.1126/science.123.3191.309

Warburg, 1956, On respiratory impairment in cancer cells, Science, 124, 269, 10.1126/science.124.3215.269

Koppenol, 2011, Otto Warburg's contributions to current concepts of cancer metabolism, Nat Rev Cancer, 11, 325, 10.1038/nrc3038

Groves, 2007, Non-[18F] FDG PET in clinical oncology, Lancet Oncol, 8, 822, 10.1016/S1470-2045(07)70274-7

Dang, 2012, Links between metabolism and cancer, Genes Dev, 26, 877, 10.1101/gad.189365.112

Deberardinis, 2010, Q's next: the diverse functions of glutamine in metabolism, cell biology and cancer, Oncogene, 29, 313, 10.1038/onc.2009.358

Vander Heiden, 2011, Targeting cancer metabolism: a therapeutic window opens, Nat Rev Drug Discov, 10, 1, 10.1038/nrd3504

Jones, 2012, Targeting cancer metabolism – aiming at a tumour's sweet-spot, Drug Discov Today, 17, 1, 10.1016/j.drudis.2011.11.004

Wang, 2012, The immune diet: meeting the metabolic demands of lymphocyte activation, F1000 Biol Rep, 4, 9, 10.3410/B4-9

Vander Heiden, 2012,  Metabolic pathway alterations that support cell proliferation, Cold Spring Harb Symp Quant Biol, 76, 325, 10.1101/sqb.2012.76.010900

Cairns, 2011, Regulation of cancer cell metabolism, Nat Rev Cancer, 11, 85, 10.1038/nrc2981

Lunt, 2011, Aerobic Glycolysis: meeting the metabolic eequirements of cell proliferation, Annu Rev Cell Dev Biol, 27, 441, 10.1146/annurev-cellbio-092910-154237

DeBerardinis, 2008, The biology of cancer: metabolic reprogramming fuels cell growth and proliferation, Cell Metab, 7, 11, 10.1016/j.cmet.2007.10.002

Locasale, 2011, Metabolic flux and the regulation of mammalian cell growth, Cell Metab, 14, 443, 10.1016/j.cmet.2011.07.014

Jones, 2009, Tumor suppressors and cell metabolism: a recipe for cancer growth, Genes Dev, 23, 537, 10.1101/gad.1756509

DeBerardinis, 2007,  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, 104, 19345, 10.1073/pnas.0709747104

Cairns, 2012, Cancer cell metabolism, Cold Spring Harb Symp Quant Biol, 76, 299, 10.1101/sqb.2011.76.012856

Michalek, 2010, The metabolic life and times of a T-cell, Immunol Rev, 236, 190, 10.1111/j.1600-065X.2010.00911.x

Franke, 2003, PI3K/Akt and apoptosis: size matters, Oncogene, 22, 8983, 10.1038/sj.onc.1207115

Plas, 2005, Akt-dependent transformation: there is more to growth than just surviving, Oncogene, 24, 7435, 10.1038/sj.onc.1209097

Luo, 2003, Targeting the PI3K-Akt pathway in human cancer: rationale and promise, Cancer Cell, 4, 257, 10.1016/S1535-6108(03)00248-4

Shaw, 2006, Ras, PI(3)K and mTOR signalling controls tumour cell growth, Nature, 441, 424, 10.1038/nature04869

Yuan, 2008, PI3K pathway alterations in cancer: variations on a theme, Oncogene, 27, 5497, 10.1038/onc.2008.245

Kohn, 1996, Expression of a constitutively active Akt Ser/Thr kinase in 3T3-L1 adipocytes stimulates glucose uptake and glucose transporter 4 translocation, J Biol Chem, 271, 31372, 10.1074/jbc.271.49.31372

Deprez, 1997, Phosphorylation and activation of heart 6-phosphofructo-2-kinase by protein kinase B and other protein kinases of the insulin signaling cascades, J Biol Chem, 272, 17269, 10.1074/jbc.272.28.17269

Gottlob, 2001, Inhibition of early apoptotic events by Akt/PKB is dependent on the first committed step of glycolysis and mitochondrial hexokinase, Genes Dev, 15, 1406, 10.1101/gad.889901

Rathmell, 2003, Akt-directed glucose metabolism can prevent Bax conformation change and promote growth factor-independent survival, Mol Cell Biol, 23, 7315, 10.1128/MCB.23.20.7315-7328.2003

Berwick, 2002, The identification of ATP-citrate lyase as a protein kinase B (Akt) substrate in primary adipocytes, J Biol Chem, 277, 33895, 10.1074/jbc.M204681200

Laplante, 2012, mTOR signaling in growth control and disease, Cell, 149, 274, 10.1016/j.cell.2012.03.017

Zoncu, 2011, mTOR: from growth signal integration to cancer, diabetes and ageing, Nat Rev Mol Cell Biol, 12, 21, 10.1038/nrm3025

Hardie, 2007, AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy, Nat Rev Mol Cell Biol, 8, 774, 10.1038/nrm2249

Mihaylova, 2011, The AMPK signalling pathway coordinates cell growth, autophagy and metabolism, Nat Cell Biol, 13, 1016, 10.1038/ncb2329

Carling, 1987, A common bicyclic protein kinase cascade inactivates the regulatory enzymes of fatty acid and cholesterol biosynthesis, FEBS Lett, 223, 217, 10.1016/0014-5793(87)80292-2

Inoki, 2003, TSC2 mediates cellular energy response to control cell growth and survival, Cell, 115, 577, 10.1016/S0092-8674(03)00929-2

Gwinn, 2008,  AMPK phosphorylation of raptor mediates a metabolic checkpoint, Mol Cell, 30, 214, 10.1016/j.molcel.2008.03.003

Shaw, 2004,  The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress, Proc Natl Acad Sci U S A, 101, 3329, 10.1073/pnas.0308061100

Greer, 2012, The updated biology of hypoxia-inducible factor, EMBO J, 31, 2448, 10.1038/emboj.2012.125

Semenza, 2012, Regulation of metabolism by hypoxia-inducible factor 1, Cold Spring Harb Symp Quant Biol, 76, 347, 10.1101/sqb.2011.76.010678

Semenza, 2010, HIF-1: upstream and downstream of cancer metabolism, Curr Opin Genet Dev, 20, 51, 10.1016/j.gde.2009.10.009

Dang, 2010, Rethinking the Warburg effect with Myc micromanaging glutamine metabolism, Cancer Res, 70, 859, 10.1158/0008-5472.CAN-09-3556

Dang, 2009, MYC-induced cancer cell energy metabolism and therapeutic opportunities, Clin Cancer Res, 15, 6479, 10.1158/1078-0432.CCR-09-0889

Yuneva, 2007, Deficiency in glutamine but not glucose induces MYC-dependent apoptosis in human cells, J Cell Biol, 178, 93, 10.1083/jcb.200703099

Wise, 2008,  Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction, Proc Natl Acad Sci U S A, 105, 18782, 10.1073/pnas.0810199105

Gao, 2009,  c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism, Nature, 458, 762, 10.1038/nature07823

Gordan, 2007, HIF and c-Myc: sibling rivals for control of cancer cell metabolism and proliferation, Cancer Cell, 12, 108, 10.1016/j.ccr.2007.07.006

Eberlé, 2004, SREBP transcription factors: master regulators of lipid homeostasis, Biochimie, 86, 839, 10.1016/j.biochi.2004.09.018

Düvel, 2010,  Activation of a metabolic gene regulatory network downstream of mTOR complex 1, Mol Cell, 39, 171, 10.1016/j.molcel.2010.06.022

Peterson, 2011,  mTOR complex 1 regulates lipin 1 localization to control the SREBP pathway, Cell, 146, 408, 10.1016/j.cell.2011.06.034

Vousden, 2009, p53 and metabolism, Nat Rev Cancer, 9, 691, 10.1038/nrc2715

Gottlieb, 2010, p53 Regulation of Metabolic Pathways, Cold Spring Harb Perspect Biol, 2, a001040, 10.1101/cshperspect.a001040

Matoba, 2006,  p53 regulates mitochondrial respiration, Science, 312, 1650, 10.1126/science.1126863

Bensaad, 2006,  TIGAR, a p53-inducible regulator of glycolysis and apoptosis, Cell, 126, 107, 10.1016/j.cell.2006.05.036

Schwartzenberg-Bar-Yoseph, 2004, The tumor suppressor p53 down-regulates glucose transporters GLUT1 and GLUT4 gene expression, Cancer Res, 64, 2627, 10.1158/0008-5472.CAN-03-0846

Kondoh, 2005,  Glycolytic enzymes can modulate cellular life span, Cancer Res, 65, 177, 10.1158/0008-5472.177.65.1

Contractor, 2012, p53 negatively regulates transcription of the pyruvate dehydrogenase kinase Pdk2, Cancer Res, 72, 560, 10.1158/0008-5472.CAN-11-1215

Jiang, 2011,  p53 regulates biosynthesis through direct inactivation of glucose-6-phosphate dehydrogenase, Nat Cell Biol, 13, 310, 10.1038/ncb2172

Feng, 2007,  The regulation of AMPK beta1, TSC2, and PTEN expression by p53: stress, cell and tissue specificity, and the role of these gene products in modulating the IGF-1-AKT-mTOR pathways, Cancer Res, 67, 3043, 10.1158/0008-5472.CAN-06-4149

Jones, 2005,  AMP-activated protein kinase induces a p53-dependent metabolic checkpoint, Mol Cell, 18, 283, 10.1016/j.molcel.2005.03.027

Tennant, 2010, Targeting metabolic transformation for cancer therapy, Nat Rev Cancer, 10, 267, 10.1038/nrc2817

Zu, 2004, Cancer metabolism: facts, fantasy, and fiction, Biochem Biophys Res Commun, 313, 459, 10.1016/j.bbrc.2003.11.136

Ben-Haim, 2009, 18F-FDG PET and PET/CT in the evaluation of cancer treatment response, J Nucl Med, 50, 88, 10.2967/jnumed.108.054205

Tessem, 2008,  Evaluation of lactate and alanine as metabolic biomarkers of prostate cancer using 1H HR-MAS spectroscopy of biopsy tissues, Magn Reson Med, 60, 510, 10.1002/mrm.21694

Kung, 2011, Glutamine synthetase is a genetic determinant of cell type–specific glutamine independence in breast epithelia, PLoS Genet, 7, e1002229, 10.1371/journal.pgen.1002229

Cheng, 2011,  Pyruvate carboxylase is required for glutamine-independent growth of tumor cells, Proc Natl Acad Sci U S A, 108, 8674, 10.1073/pnas.1016627108

Samudio, 2010,  Pharmacologic inhibition of fatty acid oxidation sensitizes human leukemia cells to apoptosis induction, J Clin Invest, 120, 142, 10.1172/JCI38942

Zaugg, 2011,  Carnitine palmitoyltransferase 1C promotes cell survival and tumor growth under conditions of metabolic stress, Genes Dev, 25, 1041, 10.1101/gad.1987211

Nomura, 2011,  Monoacylglycerol lipase exerts dual control over endocannabinoid and fatty acid pathways to support prostate cancer, Chem Biol, 18, 846, 10.1016/j.chembiol.2011.05.009

Mills, 2003, The emerging role of lysophosphatidic acid in cancer, Nat Rev Cancer, 3, 582, 10.1038/nrc1143

Gupta, 2007,  Mediators of vascular remodelling co-opted for sequential steps in lung metastasis, Nature, 446, 765, 10.1038/nature05760

DeBerardinis, 2008, Brick by brick: metabolism and tumor cell growth, Curr Opin Genet Dev, 18, 54, 10.1016/j.gde.2008.02.003

Gottlieb, 2005, Mitochondrial tumour suppressors: a genetic and biochemical update, Nat Rev Cancer, 5, 857, 10.1038/nrc1737

Selak, 2005,  Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase, Cancer Cell, 7, 77, 10.1016/j.ccr.2004.11.022

Isaacs, 2005,  HIF overexpression correlates with biallelic loss of fumarate hydratase in renal cancer: novel role of fumarate in regulation of HIF stability, Cancer Cell, 8, 143, 10.1016/j.ccr.2005.06.017

Lee, 2005,  Neuronal apoptosis linked to EglN3 prolyl hydroxylase and familial pheochromocytoma genes: developmental culling and cancer, Cancer Cell, 8, 155, 10.1016/j.ccr.2005.06.015

Parsons, 2008,  An integrated genomic analysis of human glioblastoma multiforme, Science, 321, 1807, 10.1126/science.1164382

Mardis, 2009,  Recurring mutations found by sequencing an acute myeloid leukemia genome, N Engl J Med, 361, 1058, 10.1056/NEJMoa0903840

Amary, 2011,  IDH1 and IDH2 mutations are frequent events in central chondrosarcoma and central and periosteal chondromas but not in other mesenchymal tumours, J Pathol, 224, 334, 10.1002/path.2913

Dang, 2009,  Cancer-associated IDH1 mutations produce 2-hydroxyglutarate, Nature, 462, 739, 10.1038/nature08617

Figueroa, 2010,  Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation, Cancer Cell, 18, 553, 10.1016/j.ccr.2010.11.015

Xu, 2011,  Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of alpha-ketoglutarate-dependent dioxygenases, Cancer Cell, 19, 17, 10.1016/j.ccr.2010.12.014

Lu, 2012,  IDH mutation impairs histone demethylation and results in a block to cell differentiation, Nature, 483, 474, 10.1038/nature10860

Turcan, 2012,  IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype, Nature, 483, 479, 10.1038/nature10866

Sasaki, 2012,  IDH1(R132H) mutation increases murine haematopoietic progenitors and alters epigenetics, Nature, 10.1038/nature11323

Xiao, 2012,  Inhibition of alpha-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors, Genes Dev, 26, 1326, 10.1101/gad.191056.112

Koivunen, 2012,  Transformation by the (R)-enantiomer of 2-hydroxyglutarate linked to EGLN activation, Nature, 483, 484, 10.1038/nature10898

Locasale, 2011,  Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis, Nat Genet, 43, 869, 10.1038/ng.890

Possemato, 2011, Functional genomics reveal that the serine synthesis pathway is essential in breast cancer, Nature, 476, 346, 10.1038/nature10350

Zhang, 2012,  Glycine decarboxylase activity drives non-small cell lung cancer tumor-initiating cells and tumorigenesis, Cell, 148, 259, 10.1016/j.cell.2011.11.050

Cantor, 2012, Engineering reduced-immunogenicity enzymes for amino acid depletion therapy in cancer, Methods Enzymol, 502, 291, 10.1016/B978-0-12-416039-2.00015-X

Rytting, 2010, Peg-asparaginase for acute lymphoblastic leukemia, Expert Opin Biol Ther, 10, 833, 10.1517/14712591003769808

Horowitz, 1968, Asparagine synthetase activity of mouse leukemias, Science, 160, 533, 10.1126/science.160.3827.533

Haskell, 1969, l-asparaginase resistance in human leukemia–asparagine synthetase, Biochem Pharmacol, 18, 2578, 10.1016/0006-2952(69)90375-X

Cooney, 1970, L-asparaginase and L-asparagine metabolism, Annu Rev Pharmacol, 10, 421, 10.1146/annurev.pa.10.040170.002225

Story, 1993, L-asparaginase kills lymphoma cells by apoptosis, Cancer Chemother Pharmacol, 32, 129, 10.1007/BF00685615

Ueno, 1997, Cell cycle arrest and apoptosis of leukemia cells induced by L-asparaginase, Leukemia, 11, 1858, 10.1038/sj.leu.2400834

Avramis, 2006, Asparaginase (native ASNase or pegylated ASNase) in the treatment of acute lymphoblastic leukemia, Int J Nanomedicine, 1, 241

Pui, 2006, Treatment of acute lymphoblastic leukemia, N Engl J Med, 354, 166, 10.1056/NEJMra052603

Winter, 2006,  Antimetabolite-based therapy in childhood T-cell acute lymphoblastic leukemia: a report of POG study 9296, Pediatr Blood Cancer, 46, 179, 10.1002/pbc.20429

Lorenzi, 2008,  Asparagine synthetase is a predictive biomarker of L-asparaginase activity in ovarian cancer cell lines, Mol Cancer Ther, 7, 3123, 10.1158/1535-7163.MCT-08-0589

Kurtzberg, 2000, Asparaginase, Cancer medicine, 5th ed, 699

Derst, 2000, Engineering the substrate specificity of Escherichia coli asparaginase. II. Selective reduction of glutaminase activity by amino acid replacements at position 248, Protein Sci, 9, 2009, 10.1110/ps.9.10.2009

Iwamoto, 2007, Mesenchymal cells regulate the response of acute lymphoblastic leukemia cells to asparaginase, J Clin Invest, 117, 1049, 10.1172/JCI30235

Su, 2008, Correlation between asparaginase sensitivity and asparagine synthetase protein content, but not mRNA, in acute lymphoblastic leukemia cell lines, Pediatr. Blood Cancer, 50, 274, 10.1002/pbc.21213

Chen, 2010,  A genome-wide approach identifies that the aspartate metabolism pathway contributes to asparaginase sensitivity, Leukemia, 25, 66, 10.1038/leu.2010.256

Zelent, 2004, Role of the TEL-AML1 fusion gene in the molecular pathogenesis of childhood acute lymphoblastic leukaemia, Oncogene, 23, 4275, 10.1038/sj.onc.1207672

Stams, 2005,  Asparagine synthetase expression is linked with L-asparaginase resistance in TEL-AML1-negative but not TEL-AML1-positive pediatric acute lymphoblastic leukemia, Blood, 105, 4223, 10.1182/blood-2004-10-3892

Stams, 2003,  Sensitivity to L-asparaginase is not associated with expression levels of asparagine synthetase in t(12;21)+ pediatric ALL, Blood, 101, 2743, 10.1182/blood-2002-08-2446

Feun, 2006, Pegylated arginine deiminase: a novel anticancer enzyme agent, Expert Opin Investig Drugs, 15, 815, 10.1517/13543784.15.7.815

Kuo, 2010, Targeted cellular metabolism for cancer chemotherapy with recombinant arginine-degrading enzymes, Oncotarget, 1, 246, 10.18632/oncotarget.135

Wolf, 2011,  Hexokinase 2 is a key mediator of aerobic glycolysis and promotes tumor growth in human glioblastoma multiforme, J Exp Med, 208, 313, 10.1084/jem.20101470

Mathupala, 2009, Hexokinase-2 bound to mitochondria: cancer's stygian link to the “Warburg Effect” and a pivotal target for effective therapy, Semin Cancer Biol, 19, 17, 10.1016/j.semcancer.2008.11.006

Yalcin, 2009, Regulation of glucose metabolism by 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases in cancer, Exp Mol Pathol, 86, 174, 10.1016/j.yexmp.2009.01.003

Atsumi, 2002,  High expression of inducible 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (iPFK-2; PFKFB3) in human cancers, Cancer Res, 62, 5881

Clem, 2008,  Small-molecule inhibition of 6-phosphofructo-2-kinase activity suppresses glycolytic flux and tumor growth, Mol Cancer Ther, 7, 110, 10.1158/1535-7163.MCT-07-0482

Ros, 2012,  Functional metabolic screen identifies 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 as an important regulator of prostate cancer cell survival, Cancer Discov, 2, 328, 10.1158/2159-8290.CD-11-0234

Vousden, 2010, Alternative fuel–another role for p53 in the regulation of metabolism, Proc Natl Acad Sci U S A, 107, 7117, 10.1073/pnas.1002656107

Márquez, 2006, Glutaminase: a multifaceted protein not only involved in generating glutamate, Neurochem Int, 48, 465, 10.1016/j.neuint.2005.10.015

Hu, 2010, Glutaminase 2, a novel p53 target gene regulating energy metabolism and antioxidant function, Proc Natl Acad Sci U S A, 107, 7455, 10.1073/pnas.1001006107

Hu, 2011,  13C-pyruvate imaging reveals alterations in glycolysis that precede c-Myc-induced tumor formation and regression, Cell Metab, 14, 131, 10.1016/j.cmet.2011.04.012

Wang, 2010,  Targeting mitochondrial glutaminase activity inhibits oncogenic transformation, Cancer Cell, 18, 207, 10.1016/j.ccr.2010.08.009

Seltzer, 2010,  Inhibition of Glutaminase Preferentially Slows Growth of Glioma Cells with Mutant IDH1, Cancer Res, 70, 8981, 10.1158/0008-5472.CAN-10-1666

Le, 2012,  Glucose-independent glutamine metabolism via TCA cycling for proliferation and survival in B Cells, Cell Metab, 15, 110, 10.1016/j.cmet.2011.12.009

Dang, 2012, Therapeutic targeting of Myc-reprogrammed cancer cell metabolism, Cold Spring Harb Symp on Quant Biol, 76, 369, 10.1101/sqb.2011.76.011296

Mazurek, 2005, Pyruvate kinase type M2 and its role in tumor growth and spreading, Semin Cancer Biol, 15, 300, 10.1016/j.semcancer.2005.04.009

Christofk, 2008,  The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth, Nature, 452, 230, 10.1038/nature06734

Vander Heiden, 2010,  Evidence for an alternative glycolytic pathway in rapidly proliferating cells, Science, 329, 1492, 10.1126/science.1188015

Christofk, 2008, Pyruvate kinase M2 is a phosphotyrosine-binding protein, Nature, 452, 181, 10.1038/nature06667

Anastasiou, 2011,  Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses, Science, 334, 1278, 10.1126/science.1211485

Bluemlein, 2011, No evidence for a shift in pyruvate kinase PKM1 to PKM2 expression during tumorigenesis, Oncotarget, 2, 393, 10.18632/oncotarget.278

Yang, 2011,  Nuclear PKM2 regulates β-catenin transactivation upon EGFR activation, Nature, 480, 118, 10.1038/nature10598

Luo, 2011,  Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1, Cell, 145, 732, 10.1016/j.cell.2011.03.054

Gao, 2012, Pyruvate kinase M2 regulates gene transcription by acting as a protein kinase, Mol Cell, 45, 598, 10.1016/j.molcel.2012.01.001

Tredan, 2007, Drug resistance and the solid tumor microenvironment, J Natl Cancer Inst, 99, 1441, 10.1093/jnci/djm135

Gatenby, 2008, A microenvironmental model of carcinogenesis, Nat Rev Cancer, 8, 56, 10.1038/nrc2255

Parks, 2011, pH control mechanisms of tumor survival and growth, J Cell Physiol, 226, 299, 10.1002/jcp.22400

Sotgia, 2012, Caveolin-1 and cancer metabolism in the tumor microenvironment: markers, models, and mechanisms, Annu Rev Pathol, 7, 423, 10.1146/annurev-pathol-011811-120856

Nakajima, 2012, Metabolic symbiosis in cancer: refocusing the Warburg lens, Mol Carcinog

Martinez-Outschoorn, 2011,  Anti-estrogen resistance in breast cancer is induced by the tumor microenvironment and can be overcome by inhibiting mitochondrial function in epithelial cancer cells, Cancer Biol Ther, 12, 924, 10.4161/cbt.12.10.17780

Sotgia, 2011, Understanding the Warburg effect and the prognostic value of stromal caveolin-1 as a marker of a lethal tumor microenvironment, Breast Cancer Res, 13, 213, 10.1186/bcr2892

Nieman, 2011,  Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth, Nat Med, 17, 1498, 10.1038/nm.2492

Metallo, 2012,  Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia, Nature, 481, 380, 10.1038/nature10602

Wise, 2011,  Hypoxia promotes isocitrate dehydrogenase-dependent carboxylation of α-ketoglutarate to citrate to support cell growth and viability, Proc Natl Acad Sci U S A, 108, 19611, 10.1073/pnas.1117773108

Mullen, 2012,  Reductive carboxylation supports growth in tumour cells with defective mitochondria, Nature, 481, 385, 10.1038/nature10642

Yuneva, 2012,  The metabolic profile of tumors depends on both the responsible genetic lesion and tissue type, Cell Metab, 15, 157, 10.1016/j.cmet.2011.12.015

Ying, 2012,  Oncogenic Kras maintains pancreatic tumors through regulation of anabolic glucose metabolism, Cell, 149, 656, 10.1016/j.cell.2012.01.058

Marin-Valencia, 2012,  Analysis of tumor metabolism reveals mitochondrial glucose oxidation in genetically diverse human glioblastomas in the mouse brain in vivo, Cell Metab, 15, 827, 10.1016/j.cmet.2012.05.001

Michelakis, 2010,  Metabolic modulation of glioblastoma with dichloroacetate, Sci Transl Med, 12, 31ra34