- Warburg, O., Wind, F. & Negelein, E. The metabolism of tumors in the body. J. Gen. Physiol. 8, 519–530 (1927).
Article CAS PubMed PubMed Central Google Scholar
- Warburg, O. The Metabolism of Tumours: Investigations from the Kaiser Wilhelm Institute for Biology, Berlin-Dahlen (Constable, 1930).
Google Scholar
- Warburg, O. On the origin of cancer cells. Science 123, 309–314 (1956).
Article CAS PubMed Google Scholar
- Warburg, O. On respiratory impairment in cancer cells. Science 124, 269–270 (1956).
Article CAS PubMed Google Scholar
- Weinhouse, S. On respiratory impairment in cancer cells. Science 124, 267–269 (1956).
Article CAS PubMed Google Scholar
- Weinhouse, S. Studies on the fate of isotopically labeled metabolites in the oxidative metabolism of tumors. Cancer Res. 11, 585–591 (1951). References 3–6 include the original Warburg theory that respiration is impaired in cancer cells followed by the debate between Warburg and Weinhouse on whether respiration is impaired in cancer cells, and a paper by Weinhouse describing the use of isotope tracing to determine oxidative metabolism in tumours.
CAS PubMed Google Scholar
- Weinhouse, S. Oxidative metabolism of neoplastic tissues. Adv. Cancer Res. 3, 269–325 (1955).
Article CAS PubMed Google Scholar
- Weinhouse, S. Glycolysis, respiration, and anomalous gene expression in experimental hepatomas: G. H. A. Clowes memorial lecture. Cancer Res. 32, 2007–2016 (1972).
CAS PubMed Google Scholar
- Koppenol, W. H., Bounds, P. L. & Dang, C. V. Otto Warburg's contributions to current concepts of cancer metabolism. Nat. Rev. Cancer 11, 325–337 (2011).
Article CAS PubMed Google Scholar
- Crabtree, H. G. The carbohydrate metabolism of certain pathological overgrowths. Biochem. J. 22, 1289–1298 (1928).
Article CAS PubMed PubMed Central Google Scholar
- Patra, K. C. & Hay, N. The pentose phosphate pathway and cancer. Trends Biochem. Sci. 39, 347–354 (2014).
Article CAS PubMed PubMed Central Google Scholar
- Timm, K. N. et al. Hyperpolarized [U-2H, U-13C]Glucose reports on glycolytic and pentose phosphate pathway activity in EL4 tumors and glycolytic activity in yeast cells. Magn. Reson. Med. 74, 1543–1547 (2015).
Article CAS PubMed Google Scholar
- Love, D. C. & Hanover, J. A. The hexosamine signaling pathway: deciphering the “O-GlcNAc code”. Sci. STKE 312, re13 (2005).
Google Scholar
- Hanover, J. A., Krause, M. W. & Love, D. C. The hexosamine signaling pathway: O-GlcNAc cycling in feast or famine. Biochim. Biophys. Acta 1800, 80–95 (2010).
Article CAS PubMed Google Scholar
- Jozwiak, P., Forma, E., Brys, M. & Krzeslak, A. O-GlcNAcylation and metabolic reprogramming in cancer. Front. Endocrinol. (Lausanne) 5, 145 (2014).
Google Scholar
- Zois, C. E., Favaro, E. & Harris, A. L. Glycogen metabolism in cancer. Biochem. Pharmacol. 92, 3–11 (2014).
Article CAS PubMed Google Scholar
- Patra, K. C. & Hay, N. Hexokinase 2 as oncotarget. Oncotarget 4, 1862–1863 (2013).
Article PubMed PubMed Central Google Scholar
- Patra, K. C. et al. Hexokinase 2 is required for tumor initiation and maintenance and its systemic deletion is therapeutic in mouse models of cancer. Cancer Cell 24, 213–228 (2013). A demonstration that it is feasible to systemically delete a major glycolytic enzyme for cancer therapy in mice.
Article CAS PubMed PubMed Central Google Scholar
- Robey, R. B. & Hay, N. Mitochondrial hexokinases, novel mediators of the antiapoptotic effects of growth factors and Akt. Oncogene 25, 4683–4696 (2006).
Article CAS PubMed Google Scholar
- Sui, D. & Wilson, J. E. Structural determinants for the intracellular localization of the isozymes of mammalian hexokinase: intracellular localization of fusion constructs incorporating structural elements from the hexokinase isozymes and the green fluorescent protein. Arch. Biochem. Biophys. 345, 111–125 (1997).
Article CAS PubMed Google Scholar
- Wilson, J. E. Isozymes of mammalian hexokinase: structure, subcellular localization and metabolic function. J. Exp. Biol. 206, 2049–2057 (2003).
Article CAS PubMed Google Scholar
- Irwin, D. M. & Tan, H. Molecular evolution of the vertebrate hexokinase gene family: identification of a conserved fifth vertebrate hexokinase gene. Comp. Biochem. Physiol. Part D Genom. Proteom. 3, 96–107 (2008).
Google Scholar
- Guo, C. et al. Coordinated regulatory variation associated with gestational hyperglycaemia regulates expression of the novel hexokinase HKDC1. Nat. Commun. 6, 6069 (2015).
Article CAS PubMed Google Scholar
- Shinohara, Y., Yamamoto, K., Kogure, K., Ichihara, J. & Terada, H. Steady state transcript levels of the type II hexokinase and type 1 glucose transporter in human tumor cell lines. Cancer Lett. 82, 27–32 (1994).
Article CAS PubMed Google Scholar
- Mathupala, S. P., Rempel, A. & Pedersen, P. L. 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. 276, 43407–43412 (2001).
Article CAS PubMed Google Scholar
- Tsai, H. J. & Wilson, J. E. Functional organization of mammalian hexokinases: both N- and C-terminal halves of the rat type II isozyme possess catalytic sites. Arch. Biochem. Biophys. 329, 17–23 (1996).
Article CAS PubMed Google Scholar
- Israelsen, W. J. & Vander Heiden, M. G. Pyruvate kinase: function, regulation and role in cancer. Semin. Cell Dev. Biol. 43, 43–51 (2015).
Article CAS PubMed PubMed Central Google Scholar
- Yamada, K. & Noguchi, T. Nutrient and hormonal regulation of pyruvate kinase gene expression. Biochem. J. 337, 1–11 (1999).
Article CAS PubMed PubMed Central Google Scholar
- Israelsen, W. J. et al. PKM2 isoform-specific deletion reveals a differential requirement for pyruvate kinase in tumor cells. Cell 155, 397–409 (2013). This paper showed that PKM2 deficiency accelerates mammary tumour formation in a mouse model of breast cancer.
Article CAS PubMed Google Scholar
- Cortes-Cros, M. et al. M2 isoform of pyruvate kinase is dispensable for tumor maintenance and growth. Proc. Natl Acad. Sci. USA 110, 489–494 (2013).
Article CAS PubMed Google Scholar
- Wang, Y. H. et al. Cell-state-specific metabolic dependency in hematopoiesis and leukemogenesis. Cell 158, 1309–1323 (2014).
Article CAS PubMed PubMed Central Google Scholar
- Vander Heiden, M. G. et al. Evidence for an alternative glycolytic pathway in rapidly proliferating cells. Science 329, 1492–1499 (2010).
Article CAS PubMed Google Scholar
- Valvona, C. J., Fillmore, H. L., Nunn, P. B. & Pilkington, G. J. The regulation and function of lactate dehydrogenase a: therapeutic potential in brain tumor. Brain Pathol. 26, 3–17 (2016).
Article CAS PubMed Google Scholar
- Doherty, J. R. & Cleveland, J. L. Targeting lactate metabolism for cancer therapeutics. J. Clin. Invest. 123, 3685–3692 (2013).
Article CAS PubMed PubMed Central Google Scholar
- Costa Leite, T., Da Silva, D., Guimaraes Coelho, R., Zancan, P. & Sola-Penna, M. Lactate favours the dissociation of skeletal muscle 6-phosphofructo-1- kinase tetramers down-regulating the enzyme and muscle glycolysis. Biochem. J. 408, 123–130 (2007).
Article CAS PubMed PubMed Central Google Scholar
- Gatenby, R. A., Gawlinski, E. T., Gmitro, A. F., Kaylor, B. & Gillies, R. J. Acid-mediated tumor invasion: a multidisciplinary study. Cancer Res. 66, 5216–5223 (2006).
Article CAS PubMed Google Scholar
- Fukumura, D. et al. Hypoxia and acidosis independently up-regulate vascular endothelial growth factor transcription in brain tumors in vivo. Cancer Res. 61, 6020–6024 (2001).
CAS PubMed Google Scholar
- Shi, Q. et al. Regulation of vascular endothelial growth factor expression by acidosis in human cancer cells. Oncogene 20, 3751–3756 (2001).
Article CAS PubMed Google Scholar
- Baumann, F. et al. Lactate promotes glioma migration by TGF-β2-dependent regulation of matrix metalloproteinase-2. Neuro Oncol. 11, 368–380 (2009).
Article CAS PubMed PubMed Central Google Scholar
- Rozhin, J., Sameni, M., Ziegler, G. & Sloane, B. F. Pericellular pH affects distribution and secretion of cathepsin B in malignant cells. Cancer Res. 54, 6517–6525 (1994).
CAS PubMed Google Scholar
- Feron, O. Pyruvate into lactate and back: from the Warburg effect to symbiotic energy fuel exchange in cancer cells. Radiother. Oncol. 92, 329–333 (2009).
Article CAS PubMed Google Scholar
- Hirschhaeuser, F., Sattler, U. G. & Mueller-Klieser, W. Lactate: a metabolic key player in cancer. Cancer Res. 71, 6921–6925 (2011).
Article CAS PubMed Google Scholar
- Christofk, H. R. et al. The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature 452, 230–233 (2008).
Article CAS PubMed Google Scholar
- Hensley, C. T., Wasti, A. T. & DeBerardinis, R. J. Glutamine and cancer: cell biology, physiology, and clinical opportunities. J. Clin. Invest. 123, 3678–3684 (2013).
Article CAS PubMed PubMed Central Google Scholar
- Locasale, J. W. et al. Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis. Nat. Genet. 43, 869–874 (2011).
Article CAS PubMed PubMed Central Google Scholar
- Possemato, R. et al. Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Nature 476, 346–350 (2011). References 45 and 46 showed overexpression of PHGDH in cancer cells, which diverts metabolism into the serine biosynthesis pathway.
Article CAS PubMed PubMed Central Google Scholar
- DeNicola, G. M. et al. NRF2 regulates serine biosynthesis in non-small cell lung cancer. Nat. Genet. 47, 1475–1481 (2015).
Article CAS PubMed PubMed Central Google Scholar
- Gromova, I. et al. High level PHGDH expression in breast is predominantly associated with keratin 5-positive cell lineage independently of malignancy. Mol. Oncol. 9, 1636–1654 (2015).
Article CAS PubMed PubMed Central Google Scholar
- Sun, L. et al. cMyc-mediated activation of serine biosynthesis pathway is critical for cancer progression under nutrient deprivation conditions. Cell Res. 25, 429–444 (2015).
Article CAS PubMed PubMed Central Google Scholar
- Chen, J. et al. Phosphoglycerate dehydrogenase is dispensable for breast tumor maintenance and growth. Oncotarget 4, 2502–2511 (2013).
Article PubMed PubMed Central Google Scholar
- Pacold, M. E. et al. A PHGDH inhibitor reveals coordination of serine synthesis and one-carbon unit fate. Nat. Chem. Biol. 12, 452–458 (2016).
Article CAS PubMed PubMed Central Google Scholar
- Fan, J. et al. Quantitative flux analysis reveals folate-dependent NADPH production. Nature 510, 298–302 (2014).
Article CAS PubMed PubMed Central Google Scholar
- Lewis, C. A. et al. Tracing compartmentalized NADPH metabolism in the cytosol and mitochondria of mammalian cells. Mol. Cell 55, 253–263 (2014).
Article CAS PubMed PubMed Central Google Scholar
- Hitosugi, T. et al. Phosphoglycerate mutase 1 coordinates glycolysis and biosynthesis to promote tumor growth. Cancer Cell 22, 585–600 (2012).
Article CAS PubMed PubMed Central Google Scholar
- Dunaway, G. A., Kasten, T. P., Sebo, T. & Trapp, R. Analysis of the phosphofructokinase subunits and isoenzymes in human tissues. Biochem. J. 251, 677–683 (1988).
Article CAS PubMed PubMed Central Google Scholar
- Ros, S. & Schulze, A. Balancing glycolytic flux: the role of 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatases in cancer metabolism. Cancer Metab. 1, 8 (2013).
Article PubMed PubMed Central Google Scholar
- Chesney, J. 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase and tumor cell glycolysis. Curr. Opin. Clin. Nutr. Metab. Care 9, 535–539 (2006).
Article CAS PubMed Google Scholar
- Yi, W. et al. Phosphofructokinase 1 glycosylation regulates cell growth and metabolism. Science 337, 975–980 (2012).
Article CAS PubMed PubMed Central Google Scholar
- Anastasiou, D. et al. Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses. Science 334, 1278–1283 (2011).
Article CAS PubMed PubMed Central Google Scholar
- Seidler, N. W. Basic biology of GAPDH. Adv. Exp. Med. Biol. 985, 1–36 (2013).
Article PubMed Google Scholar
- Semenza, G. L. HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations. J. Clin. Invest. 123, 3664–3671 (2013).
Article CAS PubMed PubMed Central Google Scholar
- Chen, C., Pore, N., Behrooz, A., Ismail-Beigi, F. & Maity, A. Regulation of glut1 mRNA by hypoxia-inducible factor-1. Interaction between H-ras and hypoxia. J. Biol. Chem. 276, 9519–9525 (2001).
Article CAS PubMed Google Scholar
- Yun, J. et al. Glucose deprivation contributes to the development of KRAS pathway mutations in tumor cells. Science 325, 1555–1559 (2009). This paper showed that the oncogenic activity of KRAS or BRAF requires GLUT1 and that glucose deprivation can induce oncogenic KRAS or BRAF mutations.
Article CAS PubMed PubMed Central Google Scholar
- Barthel, A. et al. Regulation of GLUT1 gene transcription by the serine/threonine kinase Akt1. J. Biol. Chem. 274, 20281–20286 (1999).
Article CAS PubMed Google Scholar
- Foran, P. G. et al. Protein kinase B stimulates the translocation of GLUT4 but not GLUT1 or transferrin receptors in 3T3-L1 adipocytes by a pathway involving SNAP-23, synaptobrevin-2, and/or cellubrevin. J. Biol. Chem. 274, 28087–28095 (1999).
Article CAS PubMed Google Scholar
- Von der Crone, S. et al. Glucose deprivation induces Akt-dependent synthesis and incorporation of GLUT1, but not of GLUT4, into the plasma membrane of 3T3-L1 adipocytes. Eur. J. Cell Biol. 79, 943–949 (2000).
Article CAS PubMed Google Scholar
- Katabi, M. M., Chan, H. L., Karp, S. E. & Batist, G. Hexokinase type II: a novel tumor-specific promoter for gene-targeted therapy differentially expressed and regulated in human cancer cells. Hum. Gene Ther. 10, 155–164 (1999).
Article CAS PubMed Google Scholar
- Pedersen, P. L., Mathupala, S., Rempel, A., Geschwind, J. F. & Ko, Y. H. Mitochondrial bound type II hexokinase: a key player in the growth and survival of many cancers and an ideal prospect for therapeutic intervention. Biochim. Biophys. Acta 1555, 14–20 (2002).
Article CAS PubMed Google Scholar
- Kim, J. W., Gao, P., Liu, Y. C., Semenza, G. L. & Dang, C. V. Hypoxia-inducible factor 1 and dysregulated c-Myc cooperatively induce vascular endothelial growth factor and metabolic switches hexokinase 2 and pyruvate dehydrogenase kinase 1. Mol. Cell. Biol. 27, 7381–7393 (2007).
Article CAS PubMed PubMed Central Google Scholar
- Gottlob, K. et al. Inhibition of early apoptotic events by Akt/PKB is dependent on the first committed step of glycolysis and mitochondrial hexokinase. Genes Dev. 15, 1406–1418 (2001).
Article CAS PubMed PubMed Central Google Scholar
- Miyamoto, S., Murphy, A. N. & Brown, J. H. Akt mediates mitochondrial protection in cardiomyocytes through phosphorylation of mitochondrial hexokinase-II. Cell Death Differ. 15, 521–529 (2008).
Article CAS PubMed Google Scholar
- Minchenko, A. et al. Hypoxia-inducible factor-1-mediated expression of the 6-phosphofructo-2-kinase/fructose- 2,6-bisphosphatase-3 (PFKFB3) gene. Its possible role in the Warburg effect. J. Biol. Chem. 277, 6183–6187 (2002).
Article CAS PubMed Google Scholar
- Atsumi, T. et al. High expression of inducible 6-phosphofructo-2-kinase/fructose- 2,6-bisphosphatase (iPFK-2; PFKFB3) in human cancers. Cancer Res. 62, 5881–5887 (2002).
CAS PubMed Google Scholar
- Minchenko, O. H. et al. Overexpression of 6-phosphofructo-2-kinase/fructose- 2,6-bisphosphatase-4 in the human breast and colon malignant tumors. Biochimie 87, 1005–1010 (2005).
Article CAS PubMed Google Scholar
- Kessler, R., Bleichert, F., Warnke, J. P. & Eschrich, K. 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3) is up-regulated in high-grade astrocytomas. J. Neurooncol. 86, 257–264 (2008).
Article CAS PubMed Google Scholar
- Miller, D. M., Thomas, S. D., Islam, A., Muench, D. & Sedoris, K. c-Myc and cancer metabolism. Clin. Cancer Res. 18, 5546–5553 (2012).
Article CAS PubMed PubMed Central Google Scholar
- Hsieh, A. L., Walton, Z. E., Altman, B. J., Stine, Z. E. & Dang, C. V. MYC and metabolism on the path to cancer. Semin. Cell Dev. Biol. 43, 11–21 (2015).
Article CAS PubMed PubMed Central Google Scholar
- Stine, Z. E., Walton, Z. E., Altman, B. J., Hsieh, A. L. & Dang, C. V. MYC metabolism, and cancer. Cancer Discov. 5, 1024–1039 (2015).
Article CAS PubMed PubMed Central Google Scholar
- Berkers, C. R., Maddocks, O. D., Cheung, E. C., Mor, I. & Vousden, K. H. Metabolic regulation by p53 family members. Cell. Metab. 18, 617–633 (2013).
Article CAS PubMed PubMed Central Google Scholar
- Liu, J., Zhang, C., Hu, W. & Feng, Z. Tumor suppressor p53 and its mutants in cancer metabolism. Cancer Lett. 356, 197–203 (2015).
Article CAS PubMed Google Scholar
- Cheung, E. C., Ludwig, R. L. & Vousden, K. H. Mitochondrial localization of TIGAR under hypoxia stimulates HK2 and lowers ROS and cell death. Proc. Natl Acad. Sci. USA 109, 20491–20496 (2012).
Article CAS PubMed PubMed Central Google Scholar
- Zhang, C. et al. Tumour-associated mutant p53 drives the Warburg effect. Nat. Commun. 4, 2935 (2013).
Article PubMed CAS Google Scholar
- Karim, S., Adams, D. H. & Lalor, P. F. Hepatic expression and cellular distribution of the glucose transporter family. World J. Gastroenterol. 18, 6771–6781 (2012).
Article CAS PubMed PubMed Central Google Scholar
- Guzman, G. et al. Evidence for heightened hexokinase II immunoexpression in hepatocyte dysplasia and hepatocellular carcinoma. Dig. Dis. Sci. 60, 420–426 (2015).
Article CAS PubMed Google Scholar
- Castaldo, G. et al. Quantitative analysis of aldolase A mRNA in liver discriminates between hepatocellular carcinoma and cirrhosis. Clin. Chem. 46, 901–906 (2000).
Article CAS PubMed Google Scholar
- Wang, Y. et al. Identification of four isoforms of aldolase B down-regulated in hepatocellular carcinoma tissues by means of two-dimensional western blotting. In Vivo 25, 881–886 (2011).
CAS PubMed Google Scholar
- Penhoet, E. E. & Rutter, W. J. Catalytic and immunochemical properties of homomeric and heteromeric combinations of aldolase subunits. J. Biol. Chem. 246, 318–323 (1971).
Article CAS PubMed Google Scholar
- Asaka, M. et al. Alteration of aldolase isozymes in serum and tissues of patients with cancer and other diseases. J. Clin. Lab Anal. 8, 144–148 (1994).
Article CAS PubMed Google Scholar
- Hu, H. et al. Phosphoinositide 3-kinase regulates glycolysis through mobilization of aldolase from the actin cytoskeleton. Cell 164, 433–446 (2016).
Article CAS PubMed PubMed Central Google Scholar
- Wang, B., Hsu, S. H., Frankel, W., Ghoshal, K. & Jacob, S. T. Stat3-mediated activation of microRNA-23a suppresses gluconeogenesis in hepatocellular carcinoma by down-regulating glucose-6-phosphatase and peroxisome proliferator-activated receptor γ, coactivator 1α. Hepatology 56, 186–197 (2012).
Article CAS PubMed Google Scholar
- Wong, C. C. et al. Switching of pyruvate kinase isoform L to M2 promotes metabolic reprogramming in hepatocarcinogenesis. PLoS ONE 9, e115036 (2014).
Article PubMed PubMed Central CAS Google Scholar
- Pan, D., Mao, C. & Wang, Y. X. Suppression of gluconeogenic gene expression by LSD1-mediated histone demethylation. PLoS ONE 8, e66294 (2013).
Article CAS PubMed PubMed Central Google Scholar
- Massari, F. et al. Metabolic alterations in renal cell carcinoma. Cancer Treat. Rev. 41, 767–776 (2015).
Article CAS PubMed Google Scholar
- Li, B. et al. Fructose-1,6-bisphosphatase opposes renal carcinoma progression. Nature 513, 251–255 (2014).
Article CAS PubMed PubMed Central Google Scholar
- Mendez-Lucas, A., Hyrossova, P., Novellasdemunt, L., Vinals, F. & Perales, J. C. Mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M) is a pro-survival, endoplasmic reticulum (ER) stress response gene involved in tumor cell adaptation to nutrient availability. J. Biol. Chem. 289, 22090–22102 (2014).
Article CAS PubMed PubMed Central Google Scholar
- Leithner, K. et al. PCK2 activation mediates an adaptive response to glucose depletion in lung cancer. Oncogene 34, 1044–1050 (2015).
Article CAS PubMed Google Scholar
- Vincent, E. E. et al. Mitochondrial phosphoenolpyruvate carboxykinase regulates metabolic adaptation and enables glucose-independent tumor growth. Mol. Cell 60, 195–207 (2015).
Article CAS PubMed Google Scholar
- Montal, E. D. et al. PEPCK coordinates the regulation of central carbon metabolism to promote cancer cell growth. Mol. Cell 60, 571–583 (2015). References 95–98 showed that the gluconeogenic enzymes, PEPCK-M and PEPCK-C, are expressed in some cancer cells to promote tumour growth when glucose is limited.
Article CAS PubMed PubMed Central Google Scholar
- Nogueira, V. & Hay, N. Molecular pathways: reactive oxygen species homeostasis in cancer cells and implications for cancer therapy. Clin. Cancer Res. 19, 4309–4314 (2013).
Article CAS PubMed PubMed Central Google Scholar
- Schafer, Z. T. et al. Antioxidant and oncogene rescue of metabolic defects caused by loss of matrix attachment. Nature 461, 109–113 (2009).
Article CAS PubMed PubMed Central Google Scholar
- Jeon, S. M., Chandel, N. S. & Hay, N. AMPK regulates NADPH homeostasis to promote tumour cell survival during energy stress. Nature 485, 661–665 (2012). References 100 and 101 showed that extracellular matrix detachment induces energetic and oxidative stress, and AMPK activation. AMPK activation is required to maintain NADPH homeostasis to promote cell survival during extracellular matrix detachment and solid tumour formation.
Article CAS PubMed PubMed Central Google Scholar
- Piskounova, E. et al. Oxidative stress inhibits distant metastasis by human melanoma cells. Nature 527, 186–191 (2015).
Article CAS PubMed PubMed Central Google Scholar
- Adekola, K., Rosen, S. T. & Shanmugam, M. Glucose transporters in cancer metabolism. Curr. Opin. Oncol. 24, 650–654 (2012).
Article CAS PubMed PubMed Central Google Scholar
- Szablewski, L. Expression of glucose transporters in cancers. Biochim. Biophys. Acta 1835, 164–169 (2013).
CAS PubMed Google Scholar
- Mueckler, M. & Thorens, B. The SLC2 (GLUT) family of membrane transporters. Mol. Aspects Med. 34, 121–138 (2013).
Article CAS PubMed PubMed Central Google Scholar
- McBrayer, S. K. et al. Multiple myeloma exhibits novel dependence on GLUT4, GLUT8, and GLUT11: implications for glucose transporter-directed therapy. Blood 119 4686–4697 (2012).
Article CAS PubMed PubMed Central Google Scholar
- Chan, D. A. et al. Targeting GLUT1 and the Warburg effect in renal cell carcinoma by chemical synthetic lethality. Sci. Transl Med. 3, 94ra70 (2011).
CAS PubMed PubMed Central Google Scholar
- Liu, Y. et al. A small-molecule inhibitor of glucose transporter 1 downregulates glycolysis, induces cell-cycle arrest, and inhibits cancer cell growth in vitro and in vivo. Mol. Cancer Ther. 11, 1672–1682 (2012).
Article CAS PubMed Google Scholar
- Wang, D. et al. A mouse model for Glut-1 haploinsufficiency. Hum. Mol. Genet. 15, 1169–1179 (2006).
Article CAS PubMed Google Scholar
- Rumsey, S. C. et al. Glucose transporter isoforms GLUT1 and GLUT3 transport dehydroascorbic acid. J. Biol. Chem. 272, 18982–18989 (1997).
Article CAS PubMed Google Scholar
- Corpe, C. P., Eck, P., Wang, J., Al-Hasani, H. & Levine, M. Intestinal dehydroascorbic acid (DHA) transport mediated by the facilitative sugar transporters, GLUT2 and GLUT8. J. Biol. Chem. 288, 9092–9101 (2013).
Article CAS PubMed PubMed Central Google Scholar
- Yun, J. et al. Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH. Science 350, 1391–1396 (2015).
Article CAS PubMed PubMed Central Google Scholar
- Uetaki, M., Tabata, S., Nakasuka, F., Soga, T. & Tomita, M. Metabolomic alterations in human cancer cells by vitamin C-induced oxidative stress. Sci. Rep. 5, 13896 (2015).
Article PubMed PubMed Central Google Scholar
- Chen, Q. et al. Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice. Proc. Natl Acad. Sci. USA 105, 11105–11109 (2008).
Article CAS PubMed PubMed Central Google Scholar
- Mikirova, N., Casciari, J., Rogers, A. & Taylor, P. Effect of high-dose intravenous vitamin C on inflammation in cancer patients. J. Transl Med. 10, 189 (2012).
Article CAS PubMed PubMed Central Google Scholar
- Trachootham, D. et al. Selective killing of oncogenically transformed cells through a ROS-mediated mechanism by beta-phenylethyl isothiocyanate. Cancer Cell 10, 241–252 (2006).
Article CAS PubMed Google Scholar
- Nogueira, V. et al. Akt determines replicative senescence and oxidative or oncogenic premature senescence and sensitizes cells to oxidative apoptosis. Cancer Cell 14, 458–470 (2008).
Article CAS PubMed PubMed Central Google Scholar
- Xu, K. & Thornalley, P. J. Involvement of glutathione metabolism in the cytotoxicity of the phenethyl isothiocyanate and its cysteine conjugate to human leukaemia cells in vitro. Biochem. Pharmacol. 61, 165–177 (2001).
Article CAS PubMed Google Scholar
- Heikkinen, S. et al. Hexokinase II-deficient mice. Prenatal death of homozygotes without disturbances in glucose tolerance in heterozygotes. J. Biol. Chem. 274, 22517–22523 (1999).
Article CAS PubMed Google Scholar
- Majewski, N. et al. Hexokinase-mitochondria interaction mediated by Akt is required to inhibit apoptosis in the presence or absence of Bax and Bak. Mol. Cell 16, 819–830 (2004).
Article CAS PubMed Google Scholar
- Majewski, N., Nogueira, V., Robey, R. B. & Hay, N. Akt inhibits apoptosis downstream of BID cleavage via a glucose-dependent mechanism involving mitochondrial hexokinases. Mol. Cell. Biol. 24, 730–740 (2004).
Article CAS PubMed PubMed Central Google Scholar
- Robey, R. B. & Hay, N. Mitochondrial hexokinases: guardians of the mitochondria. Cell Cycle 4, 654–658 (2005).
Article CAS PubMed Google Scholar
- Clem, B. et al. Small-molecule inhibition of 6-phosphofructo-2-kinase activity suppresses glycolytic flux and tumor growth. Mol. Cancer Ther. 7, 110–120 (2008).
Article CAS PubMed Google Scholar
- Clem, B. F. et al. Targeting 6-phosphofructo-2-kinase (PFKFB3) as a therapeutic strategy against cancer. Mol. Cancer Ther. 12, 1461–1470 (2013).
Article CAS PubMed PubMed Central Google Scholar
- Chesney, J., Clark, J., Lanceta, L., Trent, J. O. & Telang, S. Targeting the sugar metabolism of tumors with a first-in-class 6-phosphofructo-2-kinase (PFKFB4) inhibitor. Oncotarget 6, 18001–18011 (2015). References 124 and 125 describe inhibitors of PFKFB3 and PFKFB4 that can be used for cancer therapy.
Article PubMed PubMed Central Google Scholar
- De Bock, K. et al. Role of PFKFB3-driven glycolysis in vessel sprouting. Cell 154, 651–663 (2013).
Article CAS PubMed Google Scholar
- Schoors, S. et al. Partial and transient reduction of glycolysis by PFKFB3 blockade reduces pathological angiogenesis. Cell. Metab. 19, 37–48 (2014).
Article CAS PubMed Google Scholar
- Mullarky, E. et al. Identification of a small molecule inhibitor of 3-phosphoglycerate dehydrogenase to target serine biosynthesis in cancers. Proc. Natl Acad. Sci. USA 113, 1778–1783 (2016).
Article CAS PubMed PubMed Central Google Scholar
- Locasale, J. W. Serine, glycine and one-carbon units: cancer metabolism in full circle. Nat. Rev. Cancer 13, 572–583 (2013).
Article CAS PubMed PubMed Central Google Scholar
- Chang, C. H. et al. Metabolic competition in the tumor microenvironment is a driver of cancer progression. Cell 162, 1229–1241 (2015).
Article CAS PubMed PubMed Central Google Scholar
- Ho, P. C. et al. Phosphoenolpyruvate is a metabolic checkpoint of anti-tumor T cell responses. Cell 162, 1217–1228 (2015). References 130 and 131 showed that there is metabolic competition in the microenvironment between tumour-infiltrating T cells and the tumour cells.
Article CAS PubMed PubMed Central Google Scholar
- Zou, W., Wolchok, J. D. & Chen, L. PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: Mechanisms, response biomarkers, and combinations. Sci. Transl Med. 8, 328rv4 (2016).
Article PubMed PubMed Central CAS Google Scholar