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Robust metabolic adaptation underlying tumor progression

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Abstract

Tumor metabolism represents the end point of many signal cascades recruited by oncogenic activation. Energy metabolism of cancer cells attracted the attention of biochemists over eight decades ago. For example, high consume of glucose and high lactate production under aerobic conditions make up one of the most fundamental characteristics of cancer cells and has been exploited for diagnosis. At the same time, study of the metabolic status of tumor cells during tumor progression reveals characteristic adaptations during carcinogenesis. Although these metabolic adaptations are not the main defects that cause cancer, they may confer advantages to survive. In this review, we discuss the main metabolic hot spots and their relationship with main tumor progression events. An accurate metabolic map of the many tumor phenotypes could offer new options in the treatment of cancer.

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References

  • Aderem, A. (2005). Systems biology: its practice and challenges. Cell, 121, 511–513.

    PubMed  CAS  Google Scholar 

  • Arora, K. K., & Pedersen, P. L. (1988). Functional significance of mitochondrial bound hexokinase in tumor cell metabolism. Evidence for preferential phosphorylation of glucose by intramitochondrially generated ATP. Journal of Biological Chemistry, 263, 17422–17428.

    PubMed  CAS  Google Scholar 

  • Ashrafian, H. (2006). Cancer’s sweet tooth: The Janus effect of glucose metabolism in tumorigenesis. Lancet, 367, 618–621.

    PubMed  CAS  Google Scholar 

  • Bensaad, K., Tsuruta, A., Selak, M. A., et al. (2006). TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell, 126, 107–120.

    PubMed  CAS  Google Scholar 

  • Boros, L. G., Cascante, M., & Paul Lee, W.-N. (2002). Metabolic profiling of cell growth and death in cancer: Applications in drug discovery. Drug Discovery Today, 7, 364–372.

    PubMed  CAS  Google Scholar 

  • Boros, L. G., Lee, P. W. N., Brandes, J. L., et al. (1998). Nonoxidative pentose phosphate pathways and their direct role in ribose synthesis in tumors: Is cancer a disease of cellular glucose metabolism? Medical Hypotheses, 50, 55–59.

    PubMed  CAS  Google Scholar 

  • Boros, L. G., Puigjaner, J., Cascante, M., et al. (1997). Oxythiamine and dehydroepiandrosterone inhibit the nonoxidative synthesis of ribose and tumor cell proliferation. Cancer Research, 57, 4242–4248.

    PubMed  CAS  Google Scholar 

  • Brahimi-Horn, M. C., Chiche, J., & Pouyssegur, J. (2007). Hypoxia signalling controls metabolic demand. Current Opinion in Cell Biology, 19, 223–229.

    PubMed  CAS  Google Scholar 

  • Brusselmans, K., De Schrijver, E., Verhoeven, G., & Swinnen, J. V. (2005). RNA interference-mediated silencing of the acetyl-CoA-carboxylase-alpha gene induces growth inhibition and apoptosis of prostate cancer cells. Cancer Research, 65, 6719–6725.

    PubMed  CAS  Google Scholar 

  • Bui, T., & Thompson, C. B. (2006). Cancer’s sweet tooth. Cancer Cell, 9, 419–420.

    PubMed  CAS  Google Scholar 

  • Burt, B. M., Humm, J. L., Kooby, D. A., et al. (2001). Using positron emission tomography with [(18)F]FDG to predict tumor behavior in experimental colorectal cancer. Neoplasia, 3, 189–195.

    PubMed  CAS  Google Scholar 

  • Bustamante, E., Pediaditakis, P., He, L., & Lemasters, J. J. (2005). Isolated mouse liver mitochondria are devoid of glucokinase. Biochemical and Biophysical Research Communications, 334, 907–910.

    PubMed  CAS  Google Scholar 

  • Carujo, S., Estanyol, J. M., Ejarque, A., et al. (2006). Glyceraldehyde 3-phosphate dehydrogenase is a SET-binding protein and regulates cyclin B-cdk1 activity. Oncogene, 25, 4033–4042.

    PubMed  CAS  Google Scholar 

  • Cascante, M., Boros, L. G., Comin-Anduix, B., et al. (2002). Metabolic control analysis in drug discovery and disease. Nature Biotechnology, 20, 243–249.

    PubMed  CAS  Google Scholar 

  • Cascante, M., Centelles, J. J., Veech, R. L., Lee, W. N., & Boros, L. G. (2000). Role of thiamin (vitamin B-1) and transketolase in tumor cell proliferation. Nutrition and Cancer, 36, 150–154.

    PubMed  CAS  Google Scholar 

  • Chambers, A. F., Groom, A. C., & MacDonald, I. C. (2002). Dissemination and growth of cancer cells in metastatic sites. Nature Reviews Cancer, 2, 563–572.

    PubMed  CAS  Google Scholar 

  • Cho, C. R., Labow, M., Reinhardt, M., van Oostrum, J., & Peitsch, M. C. (2006). The application of systems biology to drug discovery. Current Opinion in Chemical Biology, 10, 294–302.

    PubMed  CAS  Google Scholar 

  • Claudino, W. M., Quattrone, A., Biganzoli, L., et al. (2007). Metabolomics: Available results, current research projects in breast cancer, and future applications. Journal of Clinical Oncology, 25, 2840–2846.

    PubMed  CAS  Google Scholar 

  • Coy, J. F., Dressler, D., Wilde, J., & Schubert, P. (2005). Mutations in the transketolase-like gene TKTL1: clinical implications for neurodegenerative diseases, diabetes and cancer. Clinical Laboratory, 51, 257–273.

    PubMed  CAS  Google Scholar 

  • Czernin, J., & Phelps, M. E. (2002). Positron emission tomography scanning: current and future applications. Annual Review of Medicine, 53, 89–112.

    PubMed  CAS  Google Scholar 

  • Dang, C. V., & Semenza, G. L. (1999). Oncogenic alterations of metabolism. Trends in Biochemical Sciences, 24, 68–72.

    PubMed  CAS  Google Scholar 

  • Danial, N. N., Gramm, C. F., Scorrano, L., et al. (2003). BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis. Nature, 424, 952–956.

    PubMed  CAS  Google Scholar 

  • Dastoor, Z., & Dreyer, J. L. (2001). Potential role of nuclear translocation of glyceraldehyde-3-phosphate dehydrogenase in apoptosis and oxidative stress. Journal of Cell Science, 114, 1643–1653.

    PubMed  CAS  Google Scholar 

  • Denkert, C., Budczies, J., Kind, T., et al. (2006). Mass spectrometry-based metabolic profiling reveals different metabolite patterns in invasive ovarian carcinomas and ovarian borderline tumors. Cancer Research, 66, 10795–10804.

    PubMed  CAS  Google Scholar 

  • Dennis, P. B., Jaeschke, A., Saitoh, M., et al. (2001). Mammalian TOR: A homeostatic ATP sensor. Science, 294, 1102–1105.

    PubMed  CAS  Google Scholar 

  • De Schrijver, E., Brusselmans, K., Heyns, W., Verhoeven, G., & Swinnen, J. V. (2003). RNA interference-mediated silencing of the fatty acid synthase gene attenuates growth and induces morphological changes and apoptosis of LNCaP prostate cancer cells. Cancer Research, 63, 3799–3804.

    PubMed  Google Scholar 

  • Downward, J. (2003). Cell biology: Metabolism meets death. Nature, 424, 896–897.

    PubMed  CAS  Google Scholar 

  • Eigenbrodt, E., Fister, P., & Reinacher, M. (1985). New perspectives on carbohydrate metabolism in tumor cells. In R. Beitner (Ed.), Regulation of carbohydrate metabolism. Florida: CRC Press.

    Google Scholar 

  • Elstrom, R. L., Bauer, D. E., Buzzai, M., et al. (2004). Akt stimulates aerobic glycolysis in cancer cells. Cancer Research, 64, 3892–3899.

    PubMed  CAS  Google Scholar 

  • Engel, R. H., & Evens, A. M. (2006). Oxidative stress and apoptosis: A new treatment paradigm in cancer. Frontiers in Bioscience, 11, 300–312.

    PubMed  CAS  Google Scholar 

  • Engel, M., Mazurek, S., Eigenbrodt, E., & Welter, C. (2004). Phosphoglycerate mutase-derived polypeptide inhibits glycolytic flux and induces cell growth arrest in tumor cell lines. Journal of Biological Chemistry, 279, 35803–35812.

    PubMed  CAS  Google Scholar 

  • Fantin, V. R., St-Pierre, J., & Leder, P. (2006). Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance. Cancer Cell, 9, 425–434.

    PubMed  CAS  Google Scholar 

  • Gambhir, S. S. (2002). Molecular imaging of cancer with positron emission tomography. Nature Reviews Cancer, 2, 683–693.

    PubMed  CAS  Google Scholar 

  • Garber, K. (2006). Energy deregulation: Licensing tumors to grow. Science, 312, 1158–1159.

    PubMed  CAS  Google Scholar 

  • Gatenby, R. A., Gawlinski, E. T., Gmitro, A. F., Kaylor, B., & Gillies, R. J. (2006). Acid-mediated tumor invasion: A multidisciplinary study. Cancer Research, 66, 5216–5223.

    PubMed  CAS  Google Scholar 

  • Gatenby, R. A., & Gillies, R. J. (2004). Why do cancers have high aerobic glycolysis? Nature Reviews Cancer, 4, 891–899.

    PubMed  CAS  Google Scholar 

  • German, J. B., Hammock, B. D., & Watkins, S. M. (2005). Metabolomics: building on a century of biochemistry to guide human health. Metabolomics, 1, 3–9.

    PubMed  CAS  Google Scholar 

  • Gottfried, E., Kunz-Schughart, L. A., Ebner, S., et al. (2006). Tumor-derived lactic acid modulates dendritic cell activation and antigen expression. Blood, 107, 2013–2021.

    PubMed  CAS  Google Scholar 

  • Gottlieb, E., & Tomlinson, I. P. (2005). Mitochondrial tumour suppressors: A genetic and biochemical update. Nature Reviews Cancer, 5, 857–866.

    PubMed  CAS  Google Scholar 

  • Grimm, H., Tibell, A., Norrlind, B., et al. (1994). Immunoregulation by parenteral lipids: Impact of the n-3 to n-6 fatty acid ratio. JPEN Journal of Parenteral and Enteral Nutrition, 18, 417–421.

    Article  PubMed  CAS  Google Scholar 

  • Gu, J., Yamamoto, H., Fukunaga, H., et al. (2006). Correlation of GLUT-1 overexpression, tumor size, and depth of invasion with 18F-2-fluoro-2-deoxy-D-glucose uptake by positron emission tomography in colorectal cancer. Digestive Diseases and Sciences, 51, 2198–2205.

    PubMed  CAS  Google Scholar 

  • Gunsalus, I. C., Horecker, B. L., & Wood, W. A. (1955). Pathways of carbohydrate metabolism in microorganisms. Bacteriological Reviews, 19, 79–128.

    PubMed  CAS  Google Scholar 

  • Hanahan, D., & Weinberg, R. A. (2000). The hallmarks of cancer. Cell, 100, 57–70.

    PubMed  CAS  Google Scholar 

  • Hansen, M., Le Nours, J., Johansson, E., et al. (2004). Inhibitor binding in a class 2 dihydroorotate dehydrogenase causes variations in the membrane-associated N-terminal domain. Protein Science, 13, 1031–1042.

    PubMed  CAS  Google Scholar 

  • Hatzivassiliou, G., Zhao, F., Bauer, D. E., et al. (2005). ATP citrate lyase inhibition can suppress tumor cell growth. Cancer Cell, 8, 311–321.

    PubMed  CAS  Google Scholar 

  • Hawkins, R. A., & Phelps, M. E. (1988). PET in clinical oncology. Cancer Metastasis Reviews, 7, 119–142.

    PubMed  CAS  Google Scholar 

  • Hegde, P., Qi, R., Gaspard, R., et al. (2001). Identification of tumor markers in models of human colorectal cancer using a 19,200-element complementary DNA microarray. Cancer Research, 61, 7792–7797.

    PubMed  CAS  Google Scholar 

  • Hewitson, K. S., Lienard, B. M., McDonough, M. A., et al. (2007). Structural and mechanistic studies on the inhibition of the hypoxia-inducible transcription factor hydroxylases by tricarboxylic acid cycle intermediates. Journal of Biological Chemistry, 282, 3293–3301.

    PubMed  CAS  Google Scholar 

  • Horecker, B. L. (2002). The pentose phosphate pathway. Journal of Biological Chemistry, 277, 47965–47971.

    PubMed  CAS  Google Scholar 

  • Hornberg, J. J., Bruggeman, F. J., Westerhoff, H. V., & Lankelma, J. (2006). Cancer: A systems biology disease. Biosystems, 83, 81–90.

    PubMed  CAS  Google Scholar 

  • Ignacak, J., & Stachurska, M. B. (2003). The dual activity of pyruvate kinase type M2 from chromatin extracts of neoplastic cells. Comparative Biochemistry and Physiology. Part B, Biochemistry and Molecular Biology, 134, 425–433.

    Google Scholar 

  • Isaacs, J. S., Jung, Y. J., Mole, D. R., et al. (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, 143–153.

    PubMed  CAS  Google Scholar 

  • Ishii, N., Ishii, T., & Hartman, P. S. (2007). The role of the electron transport SDHC gene on lifespan and cancer. Mitochondrion, 7, 24–28.

    PubMed  CAS  Google Scholar 

  • Jeong, D. W., Kim, T. S., Cho, I. T., & Kim, I. Y. (2004). Modification of glycolysis affects cell sensitivity to apoptosis induced by oxidative stress and mediated by mitochondria. Biochemical and Biophysical Research Communications, 313, 984–991.

    PubMed  CAS  Google Scholar 

  • Jones, R. G., Plas, D. R., Kubek, S., et al. (2005). AMP-activated protein kinase induces a p53-dependent metabolic checkpoint. Molecular Cell, 18, 283–293.

    PubMed  CAS  Google Scholar 

  • Jordan, K. W., & Cheng, L. L. (2007). NMR-based metabolomics approach to target biomarkers for human prostate cancer. Expert Review of Proteomics, 4, 389–400.

    PubMed  CAS  Google Scholar 

  • Kell, D. B. (2006). Systems biology, metabolic modelling and metabolomics in drug discovery and development. Drug Discovery Today, 11, 1085–1092.

    PubMed  CAS  Google Scholar 

  • Kim, J. W., & Dang, C. V. (2005). Multifaceted roles of glycolytic enzymes. Trends in Biochemical Sciences, 30, 142–150.

    PubMed  CAS  Google Scholar 

  • Kim, J. W., & Dang, C. V. (2006). Cancer’s molecular sweet tooth and the Warburg effect. Cancer Research, 66, 8927–8930.

    PubMed  CAS  Google Scholar 

  • Kim, K. H., Rodriguez, A. M., Carrico, P. M., & Melendez, J. A. (2001). Potential mechanisms for the inhibition of tumor cell growth by manganese superoxide dismutase. Antioxidants & Redox Signaling, 3, 361–373.

    CAS  Google Scholar 

  • Kim, J. W., Tchernyshyov, I., Semenza, G. L., & Dang, C. V. (2006). HIF-1-mediated expression of pyruvate dehydrogenase kinase: A metabolic switch required for cellular adaptation to hypoxia. Cell Metabolism, 3, 177–185.

    PubMed  Google Scholar 

  • King, A., Selak, M. A., & Gottlieb, E. (2006). Succinate dehydrogenase and fumarate hydratase: Linking mitochondrial dysfunction and cancer. Oncogene, 25, 4675–4682.

    PubMed  CAS  Google Scholar 

  • Kitano, H. (2002). Systems biology: A brief overview. Science, 295, 1662–1664.

    PubMed  CAS  Google Scholar 

  • Koivunen, P., Hirsila, M., Remes, A. M., et al. (2007). Inhibition of hypoxia-inducible factor (HIF) hydroxylases by citric acid cycle intermediates: Possible links between cell metabolism and stabilization of HIF. Journal of Biological Chemistry, 282, 4524–4532.

    PubMed  CAS  Google Scholar 

  • Kondoh, H., Lleonart, M. E., Gil, J., et al. (2005). Glycolytic enzymes can modulate cellular life span. Cancer Research, 65, 177–185.

    PubMed  CAS  Google Scholar 

  • Kress, S., Stein, A., Maurer, P., et al. (1998). Expression of hypoxia-inducible genes in tumor cells. Journal of Cancer Research and Clinical Oncology, 124, 315–320.

    PubMed  CAS  Google Scholar 

  • Krockenberger, M., Honig, A., Rieger, L., et al. (2007). Transketolase-like 1 expression correlates with subtypes of ovarian cancer and the presence of distant metastases. International Journal of Gynecological Cancer, 17, 101–106.

    PubMed  CAS  Google Scholar 

  • Kuhajda, F. P. (2006). Fatty acid synthase and cancer: new application of an old pathway. Cancer Research, 66, 5977–5980.

    PubMed  CAS  Google Scholar 

  • Kuo, W., Lin, J., & Tang, T. K. (2000). Human glucose-6-phosphate dehydrogenase (G6PD) gene transforms NIH 3T3 cells and induces tumors in nude mice. International Journal of Cancer, 85, 857–864.

    CAS  Google Scholar 

  • Langbein, S., Zerilli, M., Zur Hausen, A., et al. (2006). Expression of transketolase TKTL1 predicts colon and urothelial cancer patient survival: Warburg effect reinterpreted. British Journal of Cancer, 94, 578–585.

    PubMed  CAS  Google Scholar 

  • Liu, E. T. (2005). Systems biology, integrative biology, predictive biology. Cell, 121, 505–506.

    PubMed  CAS  Google Scholar 

  • Lobo, C., Ruiz-Bellido, M. A., Aledo, J. C., et al. (2000). Inhibition of glutaminase expression by antisense mRNA decreases growth and tumourigenicity of tumour cells. Biochemical Journal, 348(Pt 2), 257–261.

    PubMed  CAS  Google Scholar 

  • Loffler, M., Fairbanks, L. D., Zameitat, E., Marinaki, A. M., & Simmonds, H. A. (2005). Pyrimidine pathways in health and disease. Trends in Molecular Medicine, 11, 430–437.

    PubMed  Google Scholar 

  • Lu, H., Forbes, R. A., & Verma, A. (2002). Hypoxia-inducible factor 1 activation by aerobic glycolysis implicates the Warburg effect in carcinogenesis. Journal of Biological Chemistry, 277, 23111–23115.

    PubMed  CAS  Google Scholar 

  • Macheda, M. L., Rogers, S., & Best, J. D. (2005). Molecular and cellular regulation of glucose transporter (GLUT) proteins in cancer. Journal of Cellular Physiology, 202, 654–662.

    PubMed  CAS  Google Scholar 

  • Mack, F. A., Rathmell, W. K., Arsham, A. M., et al. (2003). Loss of pVHL is sufficient to cause HIF dysregulation in primary cells but does not promote tumor growth. Cancer Cell, 3, 75–88.

    PubMed  CAS  Google Scholar 

  • Majewski, N., Nogueira, V., Bhaskar, P., et al. (2004a). Hexokinase-mitochondria interaction mediated by Akt is required to inhibit apoptosis in the presence or absence of Bax and Bak. Molecular Cell, 16, 819–830.

    PubMed  CAS  Google Scholar 

  • Majewski, N., Nogueira, V., Robey, R. B., & Hay, N. (2004b). Akt inhibits apoptosis downstream of BID cleavage via a glucose-dependent mechanism involving mitochondrial hexokinases. Molecular and Cellular Biology, 24, 730–740.

    PubMed  CAS  Google Scholar 

  • Majumder, P. K., Febbo, P. G., Bikoff, R., et al. (2004). mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways. Nature Medicine, 10, 594–601.

    PubMed  CAS  Google Scholar 

  • Malaisse-Lagae, F., & Malaisse, W. J. (1988). Hexose metabolism in pancreatic islets: regulation of mitochondrial hexokinase binding. Biochemical Medicine and Metabolic Biology, 39, 80–89.

    PubMed  CAS  Google Scholar 

  • Malyankar, U. M. (2007). Tumor-associated antigens and biomarkers in cancer and immune therapy. International Reviews of Immunology, 26, 223–247.

    PubMed  CAS  Google Scholar 

  • Mates, J. M., & Sanchez-Jimenez, F. M. (2000). Role of reactive oxygen species in apoptosis: Implications for cancer therapy. International Journal of Biochemistry and Cell Biology, 32, 157–170.

    PubMed  CAS  Google Scholar 

  • Matoba, S., Kang, J. G., Patino, W. D., et al. (2006). p53 regulates mitochondrial respiration. Science, 312, 1650–1653.

    PubMed  CAS  Google Scholar 

  • Mazurek, S., Boschek, C. B., Hugo, F., & Eigenbrodt, E. (2005). Pyruvate kinase type M2 and its role in tumor growth and spreading. Seminars in Cancer Biology, 15, 300–308.

    PubMed  CAS  Google Scholar 

  • Mazurek, S., & Eigenbrodt, E. (2003). The tumor metabolome. Anticancer Research, 23, 1149–1154.

    PubMed  CAS  Google Scholar 

  • Menendez, J. A., Vellon, L., & Lupu, R. (2005). Antitumoral actions of the anti-obesity drug orlistat (Xenical™) in breast cancer cells: blockade of cell cycle progression, promotion of apoptotic cell death and PEA3-mediated transcriptional repression of Her2/neu (erbB-2) oncogene. Annals of Oncology, 16, 1253–1267.

    PubMed  CAS  Google Scholar 

  • Morita, T., Nagaki, T., Fukuda, I., & Okumura, K. (1992). Clastogenicity of low pH to various cultured mammalian cells. Mutation Research, 268, 297–305.

    PubMed  CAS  Google Scholar 

  • Morvan, D., & Demidem, A. (2007). Metabolomics by proton nuclear magnetic resonance spectroscopy of the response to chloroethylnitrosourea reveals drug efficacy and tumor adaptive metabolic pathways. Cancer Research, 67, 2150–2159.

    PubMed  CAS  Google Scholar 

  • Nutt, L. K., Margolis, S. S., Jensen, M., et al. (2005). Metabolic regulation of oocyte cell death through the CaMKII-mediated phosphorylation of caspase-2. Cell, 123, 89–103.

    PubMed  CAS  Google Scholar 

  • Ockner, R. K. (2004). Integration of metabolism, energetics, and signal transduction. New York: Kluwer Academic/Plenum Publishers.

    Google Scholar 

  • Oksman-Caldentey, K. M., & Saito, K. (2005). Integrating genomics and metabolomics for engineering plant metabolic pathways. Current Opinion in Biotechnology, 16, 174–179.

    PubMed  CAS  Google Scholar 

  • Oltvai, Z. N., & Barabasi, A. L. (2002). Systems biology. Life’s complexity pyramid. Science, 298, 763–764.

    PubMed  CAS  Google Scholar 

  • Osthus, R. C., Shim, H., Kim, S., et al. (2000). Deregulation of glucose transporter 1 and glycolytic gene expression by c-Myc. Journal of Biological Chemistry, 275, 21797–21800.

    PubMed  CAS  Google Scholar 

  • Ott, K. H., Aranibar, N., Singh, B., & Stockton, G. W. (2003). Metabonomics classifies pathways affected by bioactive compounds. Artificial neural network classification of NMR spectra of plant extracts. Phytochemistry, 62, 971–985.

    PubMed  CAS  Google Scholar 

  • Papandreou, I., Cairns, R. A., Fontana, L., Lim, A. L., & Denko, N. C. (2006). HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. Cell Metabolism, 3, 187–197.

    PubMed  CAS  Google Scholar 

  • Park, H. J., Lyons, J. C., Ohtsubo, T., & Song, C. W. (2000). Cell cycle progression and apoptosis after irradiation in an acidic environment. Cell Death and Differentiation, 7, 729–738.

    PubMed  CAS  Google Scholar 

  • Pelicano, H., Carney, D., & Huang, P. (2004). ROS stress in cancer cells and therapeutic implications. Drug Resistance Updates, 7, 97–110.

    PubMed  CAS  Google Scholar 

  • Pelicano, H., Xu, R. H., Du, M., et al. (2006). Mitochondrial respiration defects in cancer cells cause activation of Akt survival pathway through a redox-mediated mechanism. Journal of Cell Biology, 175, 913–923.

    PubMed  CAS  Google Scholar 

  • Perez-Gomez, C., Campos-Sandoval, J. A., Alonso, F. J., et al. (2005). Co-expressionof glutaminase K and L isoenzymes in human tumour cells. Biochemical Journal, 386, 535–542.

    PubMed  CAS  Google Scholar 

  • Pfeiffer, T., Schuster, S., & Bonhoeffer, S. (2001). Cooperation and competition in the evolution of ATP-producing pathways. Science, 292, 504–507.

    PubMed  CAS  Google Scholar 

  • Pierens, G. K., Palframan, M. E., Tranter, C. J., Carroll, A. R., & Quinn, R. J. (2005). A robust clustering approach for NMR spectra of natural product extracts. Magnetic Resonance in Chemistry, 43, 359–365.

    PubMed  CAS  Google Scholar 

  • Plas, D. R., & Thompson, C. B. (2005). Akt-dependent transformation: There is more to growth than just surviving. Oncogene, 24, 7435–7442.

    PubMed  CAS  Google Scholar 

  • Porstmann, T., Griffiths, B., Chung, Y. L., et al. (2005). PKB/Akt induces transcription of enzymes involved in cholesterol and fatty acid biosynthesis via activation of SREBP. Oncogene, 24, 6465–6481.

    PubMed  CAS  Google Scholar 

  • Pouyssegur, J., Dayan, F., & Mazure, N. M. (2006). Hypoxia signalling in cancer and approaches to enforce tumour regression. Nature, 441, 437–443.

    PubMed  CAS  Google Scholar 

  • Purcell, W. T., & Ettinger, D. S. (2003). Novel antifolate drugs. Current Oncology Reports, 5, 114–125.

    PubMed  Google Scholar 

  • Raamsdonk, L. M., Teusink, B., Broadhurst, D., et al. (2001). A functional genomics strategy that uses metabolome data to reveal the phenotype of silent mutations. Nature Biotechnology, 19, 45–50.

    PubMed  CAS  Google Scholar 

  • Racker, E. (1974). History of the Pasteur effect and its pathobiology. Molecular and Cellular Biochemistry, 5, 17–23.

    PubMed  CAS  Google Scholar 

  • Rais, B., Comin, B., Puigjaner, J., et al. (1999). Oxythiamine and dehydroepiandrosterone induce a G1 phase cycle arrest in Ehrlich’s tumor cells through inhibition of the pentose cycle. FEBS Letters, 456, 113–118.

    PubMed  CAS  Google Scholar 

  • Ramanathan, A., Wang, C., & Schreiber, S. L. (2005). Perturbational profiling of a cell-line model of tumorigenesis by using metabolic measurements. Proceedings of the National Academy of Science USA, 102, 5992–5997.

    CAS  Google Scholar 

  • Ramos-Montoya, A., Lee, W. N., Bassilian, S., et al. (2006). Pentose phosphate cycle oxidative and nonoxidative balance: A new vulnerable target for overcoming drug resistance in cancer. International Journal of Cancer, 119, 2733–2741.

    CAS  Google Scholar 

  • Rathmell, J. C., Fox, C. J., Plas, D. R., et al. (2003). Akt-directed glucose metabolism can prevent Bax conformation change and promote growth factor-independent survival. Molecular and Cellular Biology, 23, 7315–7328.

    PubMed  CAS  Google Scholar 

  • Rimpi, S., & Nilsson, J. A. (2007). Metabolic enzymes regulated by the Myc oncogene are possible targets for chemotherapy or chemoprevention. Biochemical Society Transactions, 35, 305–310.

    PubMed  CAS  Google Scholar 

  • Robey, R. B., & Hay, N. (2006). Mitochondrial hexokinases, novel mediators of the antiapoptotic effects of growth factors and Akt. Oncogene, 25, 4683–4696.

    PubMed  CAS  Google Scholar 

  • Rossignol, R., Gilkerson, R., Aggeler, R., et al. (2004). Energy substrate modulates mitochondrial structure and oxidative capacity in cancer cells. Cancer Research, 64, 985–993.

    PubMed  CAS  Google Scholar 

  • Ruiz-Lozano, P., Hixon, M. L., Wagner, M. W., et al. (1999). p53 is a transcriptional activator of the muscle-specific phosphoglycerate mutase gene and contributes in vivo to the control of its cardiac expression. Cell Growth and Differentiation, 10, 295–306.

    PubMed  CAS  Google Scholar 

  • Schafer, D., Hamm-Kunzelmann, B., & Brand, K. (1997). Glucose regulates the promoter activity of aldolase A and pyruvate kinase M2 via dephosphorylation of Sp1. FEBS Letters, 417, 325–328.

    PubMed  CAS  Google Scholar 

  • Schmidt, C. W. (2004). Metabolomics: What’s happening downstream of DNA. Environmental Health Perspectives, 112, A410–A415.

    PubMed  Google Scholar 

  • Selak, M. A., Armour, S. M., MacKenzie, E. D., et al. (2005). Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase. Cancer Cell, 7, 77–85.

    PubMed  CAS  Google Scholar 

  • Semenza, G. L., Artemov, D., Bedi, A., et al. (2001). ‘The metabolism of tumours’: 70 years later. Novartis Foundation Symposium, 240, 251–260; discussion 260–264.

    PubMed  CAS  Google Scholar 

  • Shi, Q., Le, X., Wang, B., et al. (2001). Regulation of vascular endothelial growth factor expression by acidosis in human cancer cells. Oncogene, 20, 3751–3756.

    PubMed  CAS  Google Scholar 

  • Shim, H., Chun, Y. S., Lewis, B. C., & Dang, C. V. (1998). A unique glucose-dependent apoptotic pathway induced by c-Myc. Proceedings of the National Academy of Science USA, 95, 1511–1516.

    CAS  Google Scholar 

  • Shim, H., Dolde, C., Lewis, B. C., et al. (1997). c-Myc transactivation of LDH-A: Implications for tumor metabolism and growth. Proceedings of the National Academy of Science USA, 94, 6658–6663.

    CAS  Google Scholar 

  • Sirover, M. A. (1999). New insights into an old protein: The functional diversity of mammalian glyceraldehyde-3-phosphate dehydrogenase. Biochimica et Biophysica Acta, 1432, 159–184.

    PubMed  CAS  Google Scholar 

  • Spittler, A., Oehler, R., Goetzinger, P., et al. (1997). Low glutamine concentrations induce phenotypical and functional differentiation of U937 myelomonocytic cells. Journal of Nutrition, 127, 2151–2157.

    PubMed  CAS  Google Scholar 

  • Staiger, W. I., Coy, J. F., Grobholz, R., et al. (2006). Expression of the mutated transketolase TKTL1, a molecular marker in gastric cancer. Oncology Reports, 16, 657–661.

    PubMed  CAS  Google Scholar 

  • Stern, R., Shuster, S., Neudecker, B. A., & Formby, B. (2002). Lactate stimulates fibroblast expression of hyaluronan and CD44: The Warburg effect revisited. Experimental Cell Research, 276, 24–31.

    PubMed  CAS  Google Scholar 

  • Stetak, A., Veress, R., Ovadi, J., et al. (2007). Nuclear translocation of the tumor marker pyruvate kinase M2 induces programmed cell death. Cancer Research, 67, 1602–1608.

    PubMed  CAS  Google Scholar 

  • Swinnen, J. V., Brusselmans, K., & Verhoeven, G. (2006). Increased lipogenesis in cancer cells: New players, novel targets. Current Opinion in Clinical Nutrition and Metabolic Care, 9, 358–365.

    PubMed  CAS  Google Scholar 

  • Trujillo, E., Davis, C., & Milner, J. (2006). Nutrigenomics, proteomics, metabolomics, and the practice of dietetics. Journal of the American Dietetic Association, 106, 403–413.

    PubMed  CAS  Google Scholar 

  • Urbanczyk-Wochniak, E., Luedemann, A., Kopka, J., et al. (2003). Parallel analysis of transcript and metabolic profiles: A new approach in systems biology. EMBO Reports, 4, 989–993.

    PubMed  CAS  Google Scholar 

  • van der Greef, J., Hankemeier, T., & McBurney, R. N. (2006). Metabolomics-based systems biology and personalized medicine: Moving towards n = 1 clinical trials? Pharmacogenomics, 7, 1087–1094.

    PubMed  Google Scholar 

  • Vizan, P., Boros, L. G., Figueras, A., et al. (2005). K-ras codon-specific mutations produce distinctive metabolic phenotypes in NIH3T3 mice [corrected] fibroblasts. Cancer Research, 65, 5512–5515.

    PubMed  CAS  Google Scholar 

  • Vrablic, A. S., Albright, C. D., Craciunescu, C. N., Salganik, R. I., & Zeisel, S. H. (2001). Altered mitochondrial function and overgeneration of reactive oxygen species precede the induction of apoptosis by 1-O-octadecyl-2-methyl-rac-glycero-3-phosphocholine in p53-defective hepatocytes. FASEB Journal, 15, 1739–1744.

    PubMed  CAS  Google Scholar 

  • Walenta, S., Schroeder, T., & Mueller-Klieser, W. (2004). Lactate in solid malignant tumors: Potential basis of a metabolic classification in clinical oncology. Current Medicinal Chemistry, 11, 2195–2204.

    PubMed  CAS  Google Scholar 

  • Wallace, D. C. (2005). Mitochondria and cancer: Warburg addressed. Cold Spring Harbor Symposia on Quantitative Biology, 70, 363–374.

    PubMed  CAS  Google Scholar 

  • Warburg, O., Posener, K., & Negelein, E. (1924). Über den Stoffwechsel der Karzinomzellen. Biochemische Zeitschrift, 152, 309–344.

    CAS  Google Scholar 

  • Weber, W. A., Avril, N., & Schwaiger, M. (1999). Relevance of positron emission tomography (PET) in oncology. Strahlentherapie und Onkologie, 175, 356–373.

    PubMed  CAS  Google Scholar 

  • Williams, A. C., Collard, T. J., & Paraskeva, C. (1999). An acidic environment leads to p53 dependent induction of apoptosis in human adenoma and carcinoma cell lines: Implications for clonal selection during colorectal carcinogenesis. Oncogene, 18, 3199–3204.

    PubMed  CAS  Google Scholar 

  • Xu, R. H., Pelicano, H., Zhou, Y., et al. (2005). Inhibition of glycolysis in cancer cells: A novel strategy to overcome drug resistance associated with mitochondrial respiratory defect and hypoxia. Cancer Research, 65, 613–621.

    PubMed  CAS  Google Scholar 

  • Yang, N. S., Shyur, L. F., Chen, C. H., Wang, S. Y., & Tzeng, C. M. (2004). Medicinal herb extract and a single-compound drug confer similar complex pharmacogenomic activities in mcf-7 cells. Journal of Biomedical Science, 11, 418–422.

    PubMed  CAS  Google Scholar 

  • Yasuda, S., Arii, S., Mori, A., et al. (2004). Hexokinase II and VEGF expression in liver tumors: Correlation with hypoxia-inducible factor 1 alpha and its significance. Journal of Hepatology, 40, 117–123.

    PubMed  CAS  Google Scholar 

  • Zhang, S., Yang, J. H., Guo, C. K., & Cai, P. C. (2007). Gene silencing of TKTL1 by RNAi inhibits cell proliferation in human hepatoma cells. Cancer Letters, 253, 108–114.

    PubMed  CAS  Google Scholar 

  • Zu, X. L., & Guppy, M. (2004). Cancer metabolism: facts, fantasy, and fiction. Biochemical and Biophysical Research Communications, 313, 459–465.

    PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by Grants SAF2005-01627 from the Spanish Ministery of Education and Science and ISCIII-RTICC (RD06/0020/0046), from the Spanish Ministry of Health and Consumption as well as from the Deutsche Forschungsgemeinschaft (Ma 1760 1-2 and 2-1). We are also grateful to Michael Eaude of the University of Barcelona Language Service for valuable assistance in the preparation of the manuscript.

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  1. Department of Biochemistry and Molecular Biology, Faculty of Biology (edifici nou annexe planta -2), Associated Unit to CSIC, Institute of Biomedicine of University of Barcelona (IBUB), Diagonal 645, 08028, Barcelona, Spain

    Pedro Vizán & Marta Cascante

  2. Institute of Biochemistry & Endocrinology, Veterinary Faculty, University of Giessen, 35392, Giessen, Germany

    Sybille Mazurek

  3. ScheBo Biotech AG, 35394, Giessen, Germany

    Sybille Mazurek

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  1. Pedro Vizán
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  2. Sybille Mazurek
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  3. Marta Cascante
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Correspondence to Marta Cascante.

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Vizán, P., Mazurek, S. & Cascante, M. Robust metabolic adaptation underlying tumor progression. Metabolomics 4, 1–12 (2008). https://doi.org/10.1007/s11306-007-0101-3

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