Energy Generating Pathways and the Tumor Suppressor p53

  • Chad A. Corcoran
  • Ying Huang
  • M. Saeed Sheikh


Energy generating metabolic pathways are essential for sustaining life in all cells by producing ATP, the currency for cellular transactions. Without ATP production, the driving force behind countless energetically unfavorable enzymatic reactions would not be present and life in its current form would not exist. Thus, there are compelling reasons to understand how the chemical energy harnessed within the covalent bonds of ATP is both produced and transferred. In this regard, the study of ATP synthesis typically begins with the breakdown of glucose through the anaerobic, or oxygen-independent reactions of glycolysis and follows a path through the citric acid cycle and the aerobic, oxygen-dependent process of oxidative phosphorylation/aerobic respiration (Fig. 1). Of the multiple enzymes involved in these processes, only those of the citric acid cycle and oxidative phosphorylation are localized within mitochondria. However, because the cytosolic process of glycolysis is...


Glycolytic Pathway Citric Acid Cycle Aerobic Respiration Tumor Suppressor Function Glycolytic Flux 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Arora, K. K. and Pedersen, P. L. 1988. Functional significance of mitochondrial bound hexokinase in tumor cell metabolism. Evidence for preferential phosphorylation of glucose by intramitochondrially generated ATP. J. Biol. Chem. 263:17422–17428.PubMedGoogle Scholar
  2. Bensaad, K., Tsuruta, A., Selak, M. A., Vidal, M. N., Nakano, K., Bartrons, R., Gottlieb, E., Vousden, K. H. 2006. TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell 126:107–120.CrossRefPubMedGoogle Scholar
  3. Board, M., Colquhoun, A., Newsholme, E. A. 1995. High Km glucose-phosphorylating (glucokinase) activities in a range of tumor cell lines and inhibition of rates of tumor growth by the specific enzyme inhibitor mannoheptulose. Cancer Res. 55:3278–3285.PubMedGoogle Scholar
  4. Boren, J., Cascante, M., Marin, S., Comín-Anduix, B., Centelles, J. J., Lim, S., Bassilian, S., Ahmed, S., Lee, W. N., Boros, L. G. 2001. Gleevec (STI571) influences metabolic enzyme activities and glucose carbon flow toward nucleic acid and fatty acid synthesis in myeloid tumor cells. J. Biol. Chem. 276:37747–37753.PubMedGoogle Scholar
  5. Bradshaw, P. C. and Pfeiffer, D. R. 2006. Loss of NAD(H) from swollen yeast mitochondria. BMC Biochem. 7:3.CrossRefPubMedGoogle Scholar
  6. Briasoulis, E., Pavlidis, N., Terret, C., Bauer, J., Fiedler, W., Schoffski, P., Raoul, J. L., Hess, D., Selvais, R., Lacombe, D., Bachmann, P., Fumoleau, P. 2003. Glufosfamide administered using a 1-hour infusion given as first-line treatment for advanced pancreatic cancer. A phase II trial of the EORTC-new drug development group. Eur. J. Cancer 39:2334–2340.CrossRefPubMedGoogle Scholar
  7. Bryson, J. M., Coy, P. E., Gottlob, K., Hay, N., Robey, R. B. 2002. Increased hexokinase activity, of either ectopic or endogenous origin, protects renal epithelial cells against acute oxidant-induced cell death. J. Biol. Chem. 277:11392–11400.CrossRefPubMedGoogle Scholar
  8. Capaldi, R. A. 1990. Structure and function of cytochrome c oxidase. Annu. Rev. Biochem. 59:569–596.CrossRefPubMedGoogle Scholar
  9. Chipuk, J. E., Kuwana, T., Bouchier-Hayes, L., Droin, N. M., Newmeyer, D. D., Schuler, M., Green, D. R. 2004. Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science 303:1010–1014.CrossRefPubMedGoogle Scholar
  10. Corcoran, C. A., Huang, Y. and Sheikh, M. S. 2004. The p53 paddy wagon: COP1, Pirh2 and MDM2 are found resisting apoptosis and growth arrest. Cancer Biol. Ther. 3:721–725.PubMedCrossRefGoogle Scholar
  11. Craig, A. L., Chrystal, J. A., Fraser, J. A., Sphyris, N., Lin, Y., Harrison, B. J., Scott, M. T., Dornreiter, I., Hupp, T. R. 2007. The MDM2 ubiquitination signal in the DNA-binding domain of p53 forms a docking site for calcium calmodulin kinase superfamily members. Mol. Cell. Biol. 27:3542–3555.CrossRefPubMedGoogle Scholar
  12. Di Cosimo, S., Ferretti, G., Papaldo, P., Carlini, P., Fabi, A., Cognetti, F. 2003. Lonidamine: efficacy and safety in clinical trials for the treatment of solid tumors. Drugs Today (Barc) 39:157–174CrossRefGoogle Scholar
  13. Durany, N., Joseph, J., Campo, E., Molina, R., Carreras, J. 1997a. Phosphoglycerate mutase, 2,3-bisphosphoglycerate phosphatase and enolase activity and isoenzymes in lung, colon and liver carcinomas. Br. J. Cancer 75:969–977.Google Scholar
  14. Durany, N., Joseph, J., Cruz-Sanchez, F. F., Carreras, J. 1997b. Phosphoglycerate mutase, 2,3-bisphosphoglycerate phosphatase and creatine kinase activity and isoenzymes in human brain tumours. Br. J. Cancer 76:1139–1149.Google Scholar
  15. Durany, N., Joseph, J., Jimenez, O. M., Climent, F., Fernandez, P. L., Rivera, F., Carreras, J. 2000. Phosphoglycerate mutase, 2,3-bisphosphoglycerate phosphatase, creatine kinase and enolase activity and isoenzymes in breast carcinoma. Br. J. Cancer 82:20–7.CrossRefPubMedGoogle Scholar
  16. Erster, S. and Moll, U. M. 2005. Stress-induced p53 runs a transcription-independent death program. Biochem. Biophys. Res. Commun. 331:843–850.CrossRefPubMedGoogle Scholar
  17. Fang, L., Li, G., Liu, G., Lee, S. W., Aaronson, S. A. 2001. p53 induction of heparin-binding EGF-like growth factor counteracts p53 growth suppression through activation of MAPK and PI3K/Akt signaling cascades. EMBO J. 20:1931–1939.CrossRefPubMedGoogle Scholar
  18. Feng, Z., Hu, W., de Stanchina, E., Teresky, A. K., Jin, S., Lowe, S., Levine, A. J. 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. 67:3043–3053.CrossRefPubMedGoogle Scholar
  19. Floridi, A., Paggi, M. G., Marcante, M. L., Silvestrini, B., Caputo, A., De Martino, C. 1981. Lonidamine, a selective inhibitor of aerobic glycolysis of murine tumor cells. J. Natl. Cancer Inst. 66:497–499.PubMedGoogle Scholar
  20. Floridi, A., Paggi, M. G., D’Atri, S., De Martino, C., Marcante, M. L., Silvestrini, B., Caputo, A. 1981. Effect of lonidamine on the energy metabolism of Ehrlich ascites tumor cells. Cancer Res. 41:4661–4666.PubMedGoogle Scholar
  21. Forte, M., Adelsberger-Mangan, D., and Colombini, M. 1987. Purification and characterization of the voltage-dependent anion channel from the outer mitochondrial membrane of yeast. J. Membr. Biol. 99:65–72.CrossRefPubMedGoogle Scholar
  22. Gatenby, R. A. and Gillies, R. J. 2004. Why do cancers have high aerobic glycolysis? Nat. Rev. Cancer 4:891–899.CrossRefGoogle Scholar
  23. Giaccone, G., Smit, E. F., de Jonge, M., Dansin, E., Briasoulis, E., Ardizzoni, A., Douillard, J. Y., Spaeth, D., Lacombe, D., Baron, B., Bachmann, P., Fumoleau, P.; 2004. Glufosfamide administered by 1-hour infusion as a second-line treatment for advanced non-small cell lung cancer; a phase II trial of the EORTC-New Drug Development Group. Eur. J. Cancer 40:667–672.EORTC-New Drug Development Group.CrossRefPubMedGoogle Scholar
  24. Glass-Marmor, L., Beitner, R. 1997. Detachment of glycolytic enzymes from cytoskeleton of melanoma cells induced by calmodulin antagonists. Eur. J. Pharmacol. 328:241–8.CrossRefPubMedGoogle Scholar
  25. Gottschalk, S., Anderson, N., Hainz, C., Eckhardt, S. G., Serkova, N. J. 2004. Imatinib (STI571)-mediated changes in glucose metabolism in human leukemia BCR-ABL-positive cells. Clin. Cancer Res. 10:6661–6668.CrossRefPubMedGoogle Scholar
  26. Herceg, Z. and Wang, Z. Q. 2001. Functions of poly(ADP-ribose) polymerase (PARP) in DNA repair, genomic integrity and cell death. Mutat. Res. 477:97–110.PubMedGoogle Scholar
  27. Horng, Y. C., Leary, S. C., Cobine, P. A., Young, F. B., George, G. N., Shoubridge, E. A., Winge, D. R. 2005. Human Sco1 and Sco2 function as copper-binding proteins. J. Biol. Chem. 280:34113–34122.CrossRefPubMedGoogle Scholar
  28. Imamura, K., Ogura, T., Kishimoto, A., Kaminishi, M., Esumi, H. 2001. Cell cycle regulation via p53 phosphorylation by a 5′-AMP activated protein kinase activator, 5-aminoimidazole- 4-carboxamide-1-beta-D-ribofuranoside, in a human hepatocellular carcinoma cell line. Biochem. Biophys. Res. Commun. 287:562–567.CrossRefPubMedGoogle Scholar
  29. Jones, R. G., Plas, D. R., Kubek, S., Buzzai, M., Mu, J., Xu, Y., Birnbaum, M. J., Thompson, C. B. 2005. AMP-activated protein kinase induces a p53-dependent metabolic checkpoint. Mol. Cell 18:283–293.CrossRefPubMedGoogle Scholar
  30. Kang, H. T. and Hwang, E. S. 2006. 2-Deoxyglucose: an anticancer and antiviral therapeutic, but not any more a low glucose mimetic. Life Sci. 78:1392–1399.CrossRefPubMedGoogle Scholar
  31. Karuman, P., Gozani, O., Odze, R. D., Zhou, X. C., Zhu, H., Shaw, R., Brien, T. P., Bozzuto, C. D., Ooi, D., Cantley, L. C., Yuan, J. 2001. The Peutz-Jegher gene product LKB1 is a mediator of p53-dependent cell death. Mol. Cell 7:1307–1319.CrossRefPubMedGoogle Scholar
  32. Katajisto, P., Vallenius, T., Vaahtomeri, K., Ekman, N., Udd, L., Tiainen, M., Makela, T. P. 2007. The LKB1 tumor suppressor kinase in human disease. Biochim. Biophys. Acta. 1775:63–75.PubMedGoogle Scholar
  33. Khalimonchuk, O. and Rodel, G. 2005. Biogenesis of cytochrome c oxidase. Mitochondrion 5:363–388.CrossRefPubMedGoogle Scholar
  34. Kondoh, H., Lleonart, M. E., Gil, J., Wang, J., Degan, P., Peters, G., Martinez, D., Carnero, A., Beach, D. 2005. Glycolytic enzymes can modulate cellular life span. Cancer Res. 65:177–185.PubMedGoogle Scholar
  35. Lavin, M. F. and Gueven, N. 2006. The complexity of p53 stabilization and activation. Cell Death Differ. 13:941–950.CrossRefPubMedGoogle Scholar
  36. Leu, J. I., Dumont, P., Hafey, M., Murphy, M. E., George, D. L. 2004. Mitochondrial p53 activates Bak and causes disruption of a Bak-Mcl1 complex. Nat. Cell Biol. 6:443–450.CrossRefPubMedGoogle Scholar
  37. Li, P. F., Dietz, R. and von Harsdorf, R. 1999. p53 regulates mitochondrial membrane potential through reactive oxygen species and induces cytochrome c-independent apoptosis blocked by Bcl-2. EMBO J. 18:6027–6036.CrossRefPubMedGoogle Scholar
  38. Lim, Y. P., Lim, T. T., Chan, Y. L., Song, A. C., Yeo, B. H., Vojtesek, B., Coomber, D., Rajagopal, G., Lane, D. 2007. The p53 knowledgebase: an integrated information resource for p53 research. Oncogene 26:1517–1521.CrossRefPubMedGoogle Scholar
  39. Ludes-Meyers, J. H., Subler, M. A., Shivakumar, C. V., Munoz, R. M., Jiang, P., Bigger, J. E., Brown, D. R., Deb, S. P., Deb, S. 1996. Transcriptional activation of the human epidermal growth factor receptor promoter by human p53. Mol. Cell. Biol. 16:6009–6019.PubMedGoogle Scholar
  40. Luo, J., Nikolaev, A. Y., Imai, S., Chen, D., Su, F., Shiloh, A., Guarente, L., Gu, W. 2001. Negative control of p53 by Sir2alpha promotes cell survival under stress. Cell 107:137–148.CrossRefPubMedGoogle Scholar
  41. Luo, Z., Saha, A. K., Xiang, X., Ruderman, N. B. 2005. AMPK, the metabolic syndrome and cancer. Trends Pharmacol. Sci. 26:69–76.CrossRefPubMedGoogle Scholar
  42. Macheda, M. L., Rogers, S. and Best, J. D. 2005. Molecular and cellular regulation of glucose transporter (GLUT) proteins in cancer. J. Cell Physiol. 202:654–662.CrossRefPubMedGoogle Scholar
  43. Majewski, N., Nogueira, V., Robey, R. B., Hay, N. 2004a. Akt inhibits apoptosis downstream of BID cleavage via a glucose-dependent mechanism involving mitochondrial hexokinases. Mol. Cell. Biol. 24:730–740.CrossRefGoogle Scholar
  44. Majewski, N., Nogueira, V., Bhaskar, P., Coy, P. E., Skeen, J. E., Gottlob, K., Chandel, N. S., Thompson, C. B., Robey, R. B., Hay, N. 2004b. 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.CrossRefGoogle Scholar
  45. Mathupala, S. P., Rempel, A. and Pedersen, P. L. 1997a. Aberrant glycolytic metabolism of cancer cells: a remarkable coordination of genetic, transcriptional, post-translational, and mutational events that lead to a critical role for type II hexokinase. J. Bioenerg. Biomembr. 29:339–343.CrossRefGoogle Scholar
  46. Mathupala, S. P., Heese, C. and Pedersen, P. L. 1997b. Glucose catabolism in cancer cells. The type II hexokinase promoter contains functionally active response elements for the tumor suppressor p53. J. Biol. Chem. 272:22776–22780.CrossRefGoogle Scholar
  47. Mathupala, S. P., Ko, Y. H. and Pedersen, P. L. 2006. Hexokinase II: cancer’s double-edged sword acting as both facilitator and gatekeeper of malignancy when bound to mitochondria. Oncogene 25:4777–4786.CrossRefPubMedGoogle Scholar
  48. Matoba, S., Kang, J. G., Patino, W. D., Wragg, A., Boehm, M., Gavrilova, O., Hurley, P. J., Bunz, F., Hwang, P. M. 2006. p53 regulates mitochondrial respiration. Science 312:1650–1653.CrossRefPubMedGoogle Scholar
  49. McGarrity, T. J. and Amos, C. 2006. Peutz-Jeghers syndrome: clinicopathology and molecular alterations. Cell. Mol. Life Sci. 63:2135–2144.CrossRefPubMedGoogle Scholar
  50. McLure, K. G., Takagi, M. and Kastan, M. B. 2004. NAD+. modulates p53 DNA binding specificity and function Mol. Cell. Biol. 24:9958–9967.CrossRefPubMedGoogle Scholar
  51. Mihara, M., Erster, S., Zaika, A., Petrenko, O., Chittenden, T., Pancoska, P., Moll, U. M. 2003. p53 has a direct apoptogenic role at the mitochondria. Mol. Cell 11:577–590.CrossRefPubMedGoogle Scholar
  52. Mohanti, B. K., Rath, G. K., Anantha, N., Kannan, V., Das, B. S., Chandramouli, B. A., Banerjee, A. K., Das, S., Jena, A., Ravichandran, R., Sahi, U. P., Kumar, R., Kapoor, N., Kalia, V. K., Dwarakanath, B. S., Jain, V. 1996. Improving cancer radiotherapy with 2-deoxy-D-glucose: phase I/II clinical trials on human cerebral gliomas. Int. J. Radiat. Oncol. Biol. Phys. 35:103–111.PubMedGoogle Scholar
  53. Nakashima, R. A., Mangan, P. S., Colombini, M., Pedersen, P. L. 1986. Hexokinase receptor complex in hepatoma mitochondria: evidence fromN,N'-dicyclohexylcarbodiimide-labeling studies for the involvement of the pore-forming protein VDAC. Biochemistry 25:1015–1021.CrossRefPubMedGoogle Scholar
  54. Oda, K., Arakawa, H., Tanaka, T., Matsuda, K., Tanikawa, C., Mori, T., Nishimori, H., Tamai, K., Tokino, T., Nakamura, Y., Taya, Y. 2000. p53AIP1, a potential mediator of p53-dependent apoptosis, and its regulation by Ser-46-phosphorylated p53. Cell 102:849–862.CrossRefPubMedGoogle Scholar
  55. Okamura, S., Ng, C. C., Koyama, K., Takei, Y., Arakawa, H., Monden, M., Nakamura, Y. 1999. Identification of seven genes regulated by wild-type p53 in a colon cancer cell line carrying a well-controlled wild-type p53 expression system. Oncol. Res. 11:281–285.PubMedGoogle Scholar
  56. Okar, D. A., Manzano, A., Navarro-Sabate, A., Riera, L., Bartrons, R., Lange, A. J. 2001. PFK-2/FBPase-2: maker and breaker of the essential biofactor fructose-2,6-bisphosphate. Trends Biochem. Sci. 26:30–35.CrossRefPubMedGoogle Scholar
  57. Oren, M. 2003. Decision making by p53: life, death and cancer. Cell Death Differ. 10:431–442.CrossRefPubMedGoogle Scholar
  58. Okorokov, A. L. and Milner, J. 1999. An ATP/ADP-dependent molecular switch regulates the stability of p53-DNA complexes. Mol. Cell. Biol. 19:7501–7510.PubMedGoogle Scholar
  59. Ortega-Camarillo, C., Guzman-Grenfell, A. M., Garcia-Macedo, R., Rosales-Torres, A. M., Avalos-Rodriguez, A., Duran-Reyes, G., Medina-Navarro, R., Cruz, M., Diaz-Flores, M., Kumate, J. 2006. Hyperglycemia induces apoptosis and p53 mobilization to mitochondria in RINm5F cells. Mol. Cell. Biochem. 281:163–171.CrossRefPubMedGoogle Scholar
  60. Parry, D. M. and Pedersen, P. L. 1983. Intracellular localization and properties of particulate hexokinase in the Novikoff ascites tumor. Evidence for an outer mitochondrial membrane location. J. Biol. Chem. 258:10904–10912.PubMedGoogle Scholar
  61. Pastorino, J. G., Shulga, N. and Hoek, J. B. 2002. Mitochondrial binding of hexokinase II inhibits Bax-induced cytochrome c release and apoptosis. J. Biol. Chem. 277:7610–7618.CrossRefPubMedGoogle Scholar
  62. Pelicano, H., Martin, D. S., Xu, R. H., Huang, P. 2006. Glycolysis inhibition for anticancer treatment. Oncogene 25:4633–4646.CrossRefPubMedGoogle Scholar
  63. Penso, J. and Beitner, R. 1998. Clotrimazole and bifonazole detach hexokinase from mitochondria of melanoma cells. Eur. J. Pharmacol. 342:113–117.CrossRefPubMedGoogle Scholar
  64. Perfettini, J. L., Kroemer, R. T. and Kroemer, G. 2004. Fatal liaisons of p53 with Bax and Bak. Nat. Cell Biol. 6:386–388.CrossRefPubMedGoogle Scholar
  65. Petitjean, A., Achatz, M. I., Borresen-Dale, A. L., Hainaut, P., Olivier, M. 2007. TP53 mutations in human cancers: functional selection and impact on cancer prognosis and outcomes. Oncogene 26:2157–2165.CrossRefPubMedGoogle Scholar
  66. Prives, C. and Hall, P. A. 1999. The p53 pathway. J. Pathol. 187:112–126.CrossRefPubMedGoogle Scholar
  67. Royds, J. A. and Iacopetta, B. 2006. p53 and disease: when the guardian angel fails. Cell Death. Differ. 13:1017–1026.CrossRefPubMedGoogle Scholar
  68. Ruiz-Lozano, P., Hixon, M. L., Wagner, M. W., Flores, A. I., Ikawa, S., Baldwin, A. S., Jr.Chien, K. R., Gualberto, A. 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 Differ. 10:295–306.PubMedGoogle Scholar
  69. Rustin, P., Parfait, B., Chretien, D., Bourgeron, T., Djouadi, F., Bastin, J., Rotig, A., Munnich, A. 1996. Fluxes of nicotinamide adenine dinucleotides through mitochondrial membranes in human cultured cells. J. Biol. Chem. 271:14785–14790.CrossRefPubMedGoogle Scholar
  70. Sanchez-Cespedes, M. 2007. A role for LKB1 gene in human cancer beyond the Peutz-Jeghers syndrome. Oncogene 26(57):7825–7832.CrossRefGoogle Scholar
  71. Schwartzenberg-Bar-Yoseph, F., Armoni, M. and Karnieli, E. 2004. The tumor suppressor p53 down-regulates glucose transporters GLUT1 and GLUT4 gene expression. Cancer Res. 64:2627–2633.CrossRefPubMedGoogle Scholar
  72. Seker, H., Bertram, B., Bürkle, A., Kaina, B., Pohl, J., Koepsell, H., Wiesser, M. 2000. Mechanistic aspects of the cytotoxic activity of glufosfamide, a new tumour therapeutic agent. Br. J. Cancer 82:629–634.CrossRefPubMedGoogle Scholar
  73. Selivanova, G. and Wiman, K. G. 2007. Reactivation of mutant p53: molecular mechanisms and therapeutic potential. Oncogene 26:2243–2254.CrossRefPubMedGoogle Scholar
  74. Shaw, R. J., Kosmatka, M., Bardeesy, N., Hurley, R. L., Witters, L. A., DePinho, R. A., Cantley, L. C. 2004. The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress. Proc. Natl. Acad. Sci. USA 101:3329–3335.CrossRefPubMedGoogle Scholar
  75. Shaw, R. J., Lamia, K. A., Vasquez, D., Koo, S. H., Bardeesy, N., Depinho, R. A., Montminy, M., Cantley, L. C. 2005. The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science 310:1642–1646.CrossRefPubMedGoogle Scholar
  76. Shoubridge, E. A. 2001. Cytochrome c oxidase deficiency. Am. J. Med. Genet. 106:46–52.CrossRefPubMedGoogle Scholar
  77. Singh, D., Banerji, A. K., Dwarakanath, B. S., Tripathi, R. P., Gupta, J. P., Mathew, T. L., Ravindranath, T., Jain, V. 2005. Optimizing cancer radiotherapy with 2-deoxy-d-glucose dose escalation studies in patients with glioblastoma multiforme. Strahlenther Onkol. 181:507–514.CrossRefPubMedGoogle Scholar
  78. Smith, T. A. 2000. Mammalian hexokinases and their abnormal expression in cancer. Br. J. Biomed. Sci. 57:170–178.PubMedGoogle Scholar
  79. Spicer, J. and Ashworth, A. 2004. LKB1 kinase: master and commander of metabolism and polarity. Curr. Biol. 14:R383–R385.CrossRefPubMedGoogle Scholar
  80. Tian, M., Zhang, H., Higuchi, T., Oriuchi, N., Nakasone, Y., Takata, K., Nakajima, N., Mogi, K., Endo, K. 2005. Hexokinase-II expression in untreated oral squamous cell carcinoma: comparison with FDG PET imaging. Ann. Nucl. Med. 194:335–338.CrossRefGoogle Scholar
  81. Vassilev, L. T. 2007. MDM2 inhibitors for cancer therapy. Trends Mol. Med. 13:23–31.CrossRefPubMedGoogle Scholar
  82. Vaziri, H., Dessain, S. K., Ng Eaton, E., Imai, S. I., Frye, R. A., Pandita, T. K., Guarente, L., Weinberg, R. A. 2001. hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase. Cell 107:149–159.CrossRefPubMedGoogle Scholar
  83. Veyhl, M., Wagner, K., Volk, C., Gorboulev, V., Baumgarten, K., Weber, W. M., Schaper, M., Bertram, B., Wiessler, M., Koepsell, H. 1998. Transport of the new chemotherapeutic agent beta-D-glucosylisophosphoramide mustard (D-19575) into tumor cells is mediated by the Na+-D-glucose cotransporter SAAT1. Proc. Natl. Acad. Sci. USA 95:2914–2919.CrossRefPubMedGoogle Scholar
  84. Vogelstein, B., Lane, D. and Levine, A. J. 2000. Surfing the p53 network. Nature 408:307–310.CrossRefPubMedGoogle Scholar
  85. Warburg, O. 1956. On respiratory impairment in cancer cells. Science 124:269–270.PubMedGoogle Scholar
  86. Wei, C., Amos, C. I., Stephens, L. C., Campos, I., Deng, J. M., Behringer, R. R., Rashid, A., Frazier, M. L. 2005. Mutation of Lkb1 and p53 genes exert a cooperative effect on tumorigenesis. Cancer Res. 65:11297–11303.CrossRefPubMedGoogle Scholar
  87. Wick, A. N., Drury, D. R. and Morita, T. N. 1955. 2-Deoxyglucose; a metabolic block for glucose. Proc. Soc. Exp. Biol. Med. 89:579–582.PubMedGoogle Scholar
  88. Wilson, J. E. and Chung, V. 1989. Rat brain hexokinase: further studies on the specificity of the hexose and hexose 6-phosphate binding sites. Arch. Biochem. Biophys. 269:517–525.CrossRefPubMedGoogle Scholar
  89. Wu, C., Okar, D. A., Stoeckman, A. K., Peng, L. J., Herrera, A. H., Herrera, J. E., Towle, H. C., Lange, A. J. 2004. A potential role for fructose-2,6-bisphosphate in the stimulation of hepatic glucokinase gene expression. Endocrinology 145:650–658.CrossRefPubMedGoogle Scholar
  90. Xu, D. and Finkel, T. 2002. A role for mitochondria as potential regulators of cellular life span. Biochem. Biophys. Res. Commun. 294:245–248.CrossRefPubMedGoogle Scholar
  91. Xu, R. H., Pelicano, H., Zhou, Y., Carew, J. S., Feng, L., Bhalla, K. N., Keating, M. J., Huang, P. 2005. Inhibition of glycolysis in cancer cells: a novel strategy to overcome drug resistance associated with mitochondrial respiratory defect and hypoxia. Cancer Res. 65:613–621.CrossRefPubMedGoogle Scholar
  92. Yoon, K. A., Nakamura, Y. and Arakawa, H. 2004. Identification of ALDH4 as a p53-inducible gene and its protective role in cellular stresses. J. Hum. Genet. 49:134–140.CrossRefPubMedGoogle Scholar
  93. Zeng, P. Y. and Berger, S. L. 2006. LKB1 is recruited to the p21/WAF1 promoter by p53 to mediate transcriptional activation. Cancer Res. 66:10701–10708.CrossRefPubMedGoogle Scholar
  94. Zhou, S., Kachhap, S. and Singh, K. K. 2003. Mitochondrial impairment in p53-deficient human cancer cells. Mutagenesis 18:287–292.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science + Business Media, LLC 2009

Authors and Affiliations

  • Chad A. Corcoran
    • 1
  • Ying Huang
    • 1
  • M. Saeed Sheikh
    • 1
  1. 1.Department of PharmacologyState University of New York Upstate Medical UniversitySyracuseUSA

Personalised recommendations