The Biology of Cancer: Metabolic Reprogramming Fuels Cell Growth and Proliferation

Adhikary, 2005, Transcriptional regulation and transformation by Myc proteins, Nat. Rev. Mol. Cell Biol., 6, 635, 10.1038/nrm1703

Astuti, 2001, Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma, Am. J. Hum. Genet., 69, 49, 10.1086/321282

Bachman, 2004, The PIK3CA gene is mutated with high frequency in human breast cancers, Cancer Biol. Ther., 3, 772, 10.4161/cbt.3.8.994

Barata, 2004, Activation of PI3K is indispensable for interleukin 7-mediated viability, proliferation, glucose use, and growth of T cell acute lymphoblastic leukemia cells, J. Exp. Med., 200, 659, 10.1084/jem.20040789

Bauer, 2004, Cytokine stimulation of aerobic glycolysis in hematopoietic cells exceeds proliferative demand, FASEB J., 18, 1303, 10.1096/fj.03-1001fje

Bauer, 2005, ATP citrate lyase is an important component of cell growth and transformation, Oncogene, 24, 6314, 10.1038/sj.onc.1208773

Baysal, 2000, Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma, Science, 287, 848, 10.1126/science.287.5454.848

Bellacosa, 1995, Molecular alterations of the AKT2 oncogene in ovarian and breast carcinomas, Int. J. Cancer, 64, 280, 10.1002/ijc.2910640412

Brand, 1992, A 13C NMR study on fluxes into the TCA cycle of neuronal and glial tumor cell lines and primary cells, Biochimie, 74, 941, 10.1016/0300-9084(92)90078-S

Brand, 1985, Glutamine and glucose metabolism during thymocyte proliferation. Pathways of glutamine and glutamate metabolism, Biochem. J., 228, 353, 10.1042/bj2280353

Brunelle, 2005, Oxygen sensing requires mitochondrial ROS but not oxidative phosphorylation, Cell Metab., 1, 409, 10.1016/j.cmet.2005.05.002

Buzzai, 2005, The glucose dependence of Akt-transformed cells can be reversed by pharmacologic activation of fatty acid beta-oxidation, Oncogene, 24, 4165, 10.1038/sj.onc.1208622

Cappuzzo, 2005, Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer, J. Natl. Cancer Inst., 97, 643, 10.1093/jnci/dji112

Chang, 1973, Enzymatic and immunological studies on pyruvate carboxylase in livers and liver tumors, Cancer Res., 33, 2034

Chang, 2005, KGF induces lipogenic genes through a PI3K and JNK/SREBP-1 pathway in H292 cells, J. Lipid Res., 46, 2624, 10.1194/jlr.M500154-JLR200

Cramer, 2003, HIF-1alpha is essential for myeloid cell-mediated inflammation, Cell, 112, 645, 10.1016/S0092-8674(03)00154-5

Curi, 1988, Metabolism of pyruvate by isolated rat mesenteric lymphocytes, lymphocyte mitochondria and isolated mouse macrophages, Biochem. J., 250, 383, 10.1042/bj2500383

DeBerardinis, 2006, Phosphatidylinositol 3-kinase-dependent modulation of carnitine palmitoyltransferase 1A expression regulates lipid metabolism during hematopoietic cell growth, J. Biol. Chem., 281, 37372, 10.1074/jbc.M608372200

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. USA, 104, 19345, 10.1073/pnas.0709747104

Eagle, 1956, The growth response of mammalian cells in tissue culture to L-glutamine and L-glutamic acid, J. Biol. Chem., 218, 607, 10.1016/S0021-9258(18)65826-0

Edinger, 2002, Akt maintains cell size and survival by increasing mTOR-dependent nutrient uptake, Mol. Biol. Cell, 13, 2276, 10.1091/mbc.01-12-0584

Elstrom, 2004, Akt stimulates aerobic glycolysis in cancer cells, Cancer Res., 64, 3892, 10.1158/0008-5472.CAN-03-2904

Fantin, 2006, Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance, Cancer Cell, 9, 425, 10.1016/j.ccr.2006.04.023

Forbes, 2006, Estradiol stimulates the biosynthetic pathways of breast cancer cells: detection by metabolic flux analysis, Metab. Eng., 8, 639, 10.1016/j.ymben.2006.06.005

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

Gimenez-Roqueplo, 2001, The R22X mutation of the SDHD gene in hereditary paraganglioma abolishes the enzymatic activity of complex II in the mitochondrial respiratory chain and activates the hypoxia pathway, Am. J. Hum. Genet., 69, 1186, 10.1086/324413

Gimm, 2000, Somatic and occult germ-line mutations in SDHD, a mitochondrial complex II gene, in nonfamilial pheochromocytoma, Cancer Res., 60, 6822

Gingras, 2001, Regulation of translation initiation by FRAP/mTOR, Genes Dev., 15, 807, 10.1101/gad.887201

Gordan, 2007, Hypoxia-inducible factors: central regulators of the tumor phenotype, Curr. Opin. Genet. Dev., 17, 71, 10.1016/j.gde.2006.12.006

Guo, 2000, Identification of c-myc responsive genes using rat cDNA microarray, Cancer Res., 60, 5922

Guppy, 1993, The role of the Crabtree effect and an endogenous fuel in the energy metabolism of resting and proliferating thymocytes, Eur. J. Biochem., 212, 95, 10.1111/j.1432-1033.1993.tb17637.x

Guzy, 2005, Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing, Cell Metab., 1, 401, 10.1016/j.cmet.2005.05.001

Hammond, 1978, Activities of key gluconeogenic enzymes and glycogen synthase in rat and human livers, hepatomas, and hepatoma cell cultures, Cancer Res., 38, 1317

Hatzivassiliou, 2005, ATP citrate lyase inhibition can suppress tumor cell growth, Cancer Cell, 8, 311, 10.1016/j.ccr.2005.09.008

Hedeskov, 1968, Early effects of phytohaemagglutinin on glucose metabolism of normal human lymphocytes, Biochem. J., 110, 373, 10.1042/bj1100373

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

Jiang, 2001, Phosphatidylinositol 3-kinase signaling controls levels of hypoxia-inducible factor 1, Cell Growth Differ., 12, 363

Kannan, 1980, Dietary control of lipogenesis in vivo in host tissues and tumors of mice bearing Ehrlich ascites carcinoma, Cancer Res., 40, 4606

Kim, 2006, HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia, Cell Metab., 3, 177, 10.1016/j.cmet.2006.02.002

Knobbe, 2002, Pten signaling in gliomas, Neuro-oncol., 4, 196, 10.1215/15228517-4-3-196

Kovacevic, 1983, Mitochondrial metabolism of glutamine and glutamate and its physiological significance, Physiol. Rev., 63, 547, 10.1152/physrev.1983.63.2.547

Kuhajda, 1994, Fatty acid synthesis: a potential selective target for antineoplastic therapy, Proc. Natl. Acad. Sci. USA, 91, 6379, 10.1073/pnas.91.14.6379

Kurzrock, 2003, Philadelphia chromosome-positive leukemias: from basic mechanisms to molecular therapeutics, Ann. Intern. Med., 138, 819, 10.7326/0003-4819-138-10-200305200-00010

Lum, 2005, Growth factor regulation of autophagy and cell survival in the absence of apoptosis, Cell, 120, 237, 10.1016/j.cell.2004.11.046

Lum, 2007, The transcription factor HIF-1alpha plays a critical role in the growth factor-dependent regulation of both aerobic and anaerobic glycolysis, Genes Dev., 21, 1037, 10.1101/gad.1529107

Majumder, 2004, mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways, Nat. Med., 10, 594, 10.1038/nm1052

Mansfield, 2005, Mitochondrial dysfunction resulting from loss of cytochrome c impairs cellular oxygen sensing and hypoxic HIF-alpha activation, Cell Metab., 1, 393, 10.1016/j.cmet.2005.05.003

Marjanovic, 1990, Expression of a new set of glycolytic isozymes in activated human peripheral lymphocytes, Biochim. Biophys. Acta, 1087, 1, 10.1016/0167-4781(90)90113-G

Moreno-Sanchez, 2007, Energy metabolism in tumor cells, FEBS J., 274, 1393, 10.1111/j.1742-4658.2007.05686.x

Newsholme, 1985, The role of high rates of glycolysis and glutamine utilization in rapidly dividing cells, Biosci. Rep., 5, 393, 10.1007/BF01116556

Niemann, 2000, Mutations in SDHC cause autosomal dominant paraganglioma, type 3, Nat. Genet., 26, 268, 10.1038/81551

Nikiforov, 2002, A functional screen for Myc-responsive genes reveals serine hydroxymethyltransferase, a major source of the one-carbon unit for cell metabolism, Mol. Cell. Biol., 22, 5793, 10.1128/MCB.22.16.5793-5800.2002

O'Connell, 2003, A large scale genetic analysis of c-Myc-regulated gene expression patterns, J. Biol. Chem., 278, 12563, 10.1074/jbc.M210462200

Ohgaki, 2005, Genetic pathways to glioblastomas, Neuropathology, 25, 1, 10.1111/j.1440-1789.2004.00600.x

Ookhtens, 1984, Liver and adipose tissue contributions to newly formed fatty acids in an ascites tumor, Am. J. Physiol., 247, R146

O'Rourke, 1996, Identification of hypoxically inducible mRNAs in HeLa cells using differential-display PCR. Role of hypoxia-inducible factor-1, Eur. J. Biochem., 241, 403, 10.1111/j.1432-1033.1996.00403.x

Osthus, 2000, Deregulation of glucose transporter 1 and glycolytic gene expression by c-Myc, J. Biol. Chem., 275, 21797, 10.1074/jbc.C000023200

Papandreou, 2006, HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption, Cell Metab., 3, 187, 10.1016/j.cmet.2006.01.012

Parlo, 1984, Enhanced rate of citrate export from cholesterol-rich hepatoma mitochondria. The truncated Krebs cycle and other metabolic ramifications of mitochondrial membrane cholesterol, J. Biol. Chem., 259, 9997, 10.1016/S0021-9258(18)90917-8

Parlo, 1986, Continuous pyruvate carbon flux to newly synthesized cholesterol and the suppressed evolution of pyruvate-generated CO2 in tumors: further evidence for a persistent truncated Krebs cycle in hepatomas, Biochim. Biophys. Acta, 886, 169, 10.1016/0167-4889(86)90134-5

Pedrero, 2005, Frequent genetic and biochemical alterations of the PI 3-K/AKT/PTEN pathway in head and neck squamous cell carcinoma, Int. J. Cancer, 114, 242, 10.1002/ijc.20711

Pfeiffer, 2001, Cooperation and competition in the evolution of ATP-producing pathways, Science, 292, 504, 10.1126/science.1058079

Pizer, 1996, Inhibition of fatty acid synthesis delays disease progression in a xenograft model of ovarian cancer, Cancer Res., 56, 1189

Plas, 2001, Akt and Bcl-xL promote growth factor-independent survival through distinct effects on mitochondrial physiology, J. Biol. Chem., 276, 12041, 10.1074/jbc.M010551200

Pollard, 2007, Targeted inactivation of fh1 causes proliferative renal cyst development and activation of the hypoxia pathway, Cancer Cell, 11, 311, 10.1016/j.ccr.2007.02.005

Portais, 1996, Glucose and glutamine metabolism in C6 glioma cells studied by carbon 13 NMR, Biochimie, 78, 155, 10.1016/0300-9084(96)89500-9

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

Reitzer, 1979, Evidence that glutamine, not sugar, is the major energy source for cultured HeLa cells, J. Biol. Chem., 254, 2669, 10.1016/S0021-9258(17)30124-2

Roos, 1973, Changes in the carbohydrate metabolism of mitogenically stimulated human peripheral lymphocytes. II. Relative importance of glycolysis and oxidative phosphorylation on phytohaemagglutinin stimulation, Exp. Cell Res., 77, 127, 10.1016/0014-4827(73)90561-2

Roos, 2007, Mammalian target of rapamycin in the human placenta regulates leucine transport and is down-regulated in restricted fetal growth, J. Physiol., 582, 449, 10.1113/jphysiol.2007.129676

Samuels, 2004, High frequency of mutations of the PIK3CA gene in human cancers, Science, 304, 554, 10.1126/science.1096502

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

Semenza, 2003, Targeting HIF-1 for cancer therapy, Nat. Rev. Cancer, 3, 721, 10.1038/nrc1187

Semenza, 1994, Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1, J. Biol. Chem., 269, 23757, 10.1016/S0021-9258(17)31580-6

Shim, 1997, c-Myc transactivation of LDH-A: implications for tumor metabolism and growth, Proc. Natl. Acad. Sci. USA, 94, 6658, 10.1073/pnas.94.13.6658

Slamon, 1989, Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer, Science, 244, 707, 10.1126/science.2470152

Tomlinson, 2002, Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer, Nat. Genet., 30, 406, 10.1038/ng849

Wang, 1976, Aerobic glycolysis during lymphocyte proliferation, Nature, 261, 702, 10.1038/261702a0

Warburg, 1925, Uber den Stoffwechsel der Carcinomzelle, Klin. Wochenschr., 4, 534, 10.1007/BF01726151

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

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

Wieman, 2007, Cytokine stimulation promotes glucose uptake via phosphatidylinositol-3 kinase/Akt regulation of Glut1 activity and trafficking, Mol. Biol. Cell, 18, 1437, 10.1091/mbc.e06-07-0593

Xu, 2005, Synergistic effect of targeting mTOR by rapamycin and depleting ATP by inhibition of glycolysis in lymphoma and leukemia cells, Leukemia, 19, 2153, 10.1038/sj.leu.2403968

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