Combined targeting of PDK1 and EGFR triggers regression of glioblastoma by reversing the warburg effect

Cancer Research

Volumn 73, Issue 24, 2013, Pages 7277-7289

  Velpula, Kiran Kumar ^a   Bhasin, Arnima ^a   Asuthkar, Swapna ^a   Tsung, Andrew J ^a,b  

^a Illinois Neurological Institute   (United States)

^b UNIVERSITY OF ILLINOIS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DICHLOROACETIC ACID; EPIDERMAL GROWTH FACTOR RECEPTOR; HYPOXIA INDUCIBLE FACTOR 1ALPHA; PHOSPHOINOSITIDE DEPENDENT PROTEIN KINASE 1; PYRUVATE DEHYDROGENASE KINASE;

AEROBIC METABOLISM; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CANCER GROWTH; CANCER REGRESSION; CELL METABOLISM; COMPLEX FORMATION; CONTROLLED STUDY; ENZYME ACTIVATION; FEMALE; GLIOBLASTOMA; GLYCOLYSIS; HUMAN; HUMAN CELL; HYPOXIA; IMMUNOHISTOCHEMISTRY; IN VIVO STUDY; MOLECULARLY TARGETED THERAPY; MOUSE; NONHUMAN; OXIDATIVE PHOSPHORYLATION; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; RNA INTERFERENCE; STEM CELL TRANSPLANTATION; TUMOR BIOPSY; WARBURG EFFECT;

ANIMALS; BRAIN NEOPLASMS; CELL HYPOXIA; CELL LINE, TUMOR; CELL TRANSFORMATION, NEOPLASTIC; DICHLOROACETIC ACID; FEMALE; GLIOBLASTOMA; HUMANS; MICE; MICE, NUDE; PROTEIN-SERINE-THREONINE KINASES; RECEPTOR, EPIDERMAL GROWTH FACTOR; SIGNAL TRANSDUCTION;

EID: 84891273707     PISSN: 00085472     EISSN: 15387445     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-13-1868     Document Type: Article

References (34)

1. Koppenol WH, Bounds PL, Dang CV. Otto Warburg's contributions to current concepts of cancer metabolism. Nat Rev Cancer 2011;11: 325-37.
2. Hsu PP, Sabatini DM. Cancer cell metabolism: Warburg and beyond. Cell 2008;134:703-7.
3. Wolf A, Agnihotri S, Munoz D, Guha A. Developmental profile and regulation of the glycolytic enzyme hexokinase 2 in normal brain and glioblastoma multiforme. Neurobiol Dis 2011;44:84-91.
4. Di CA, Scarabino T, Trojsi F, Popolizio T, Catapano D, Giannatempo GM, et al. Proton MR spectroscopy of cerebral gliomas at 3 T: Spatial heterogeneity, and tumour grade and extent. Eur Radiol 2008;18: 1727-35.
5. Ran C, Liu H, Hitoshi Y, Israel MA. Proliferation-independent control of tumor glycolysis by PDGFR-mediated AKT activation. Cancer Res 2013;73:1831-43.
6. Israel M, Schwartz L. The metabolic advantage of tumor cells. Mol Cancer 2011;10:70.
7. Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: The metabolic requirements of cell proliferation. Science 2009;324:1029-33.
8. Weihua Z, Tsan R, Huang WC, Wu Q, Chiu CH, Fidler IJ, et al. Survival of cancer cells is maintained by EGFR independent of its kinase activity. Cancer Cell 2008;13:385-93.
9. Sutendra G, Michelakis ED. Pyruvate dehydrogenase kinase as a novel therapeutic target in oncology. Front Oncol 2013;3:38.
10. Contractor T, Harris CR. p53 negatively regulates transcription of the pyruvate dehydrogenase kinase Pdk2. Cancer Res 2012;72:560-7.
11. Hur H, Xuan Y, Kim YB, Lee G, Shim W, Yun J, et al. Expression of pyruvate dehydrogenase kinase-1 in gastric cancer as a potential therapeutic target. Int J Oncol 2013;42:44-54.
12. Kaelin WG Jr, Thompson CB. Q&A: Cancer: Clues from cell metabolism. Nature 2010;465:562-4.
13. Bonnet S, Archer SL, Allalunis-Turner J, Haromy A, Beaulieu C, Thompson R, et al. A mitochondria-K channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth. Cancer Cell 2007;11:37-51.
14. Velpula KK, Dasari VR, Asuthkar S, Gorantla B, Tsung AJ. EGFR and c- Met cross talk in glioblastoma and its regulation by human cord blood stem cells. Transl Oncol 2012;5:379-92.
15. Giannini C, Sarkaria JN, Saito A, Uhm JH, Galanis E, Carlson BL, et al. Patient tumor EGFR and PDGFRA gene amplifications retained in an invasive intracranial xenograft model of glioblastoma multiforme. Neuro oncol 2005;7:164-76.
16. Chigurupati S, Venkataraman R, Barrera D, Naganathan A, Madan M, Paul L, et al. Receptor channel TRPC6 is a key mediator of Notchdriven glioblastoma growth and invasiveness. Cancer Res 2010;70: 418-27.
17. Yang W, Zheng Y, Xia Y, Ji H, Chen X, Guo F, et al. ERK1/2-dependent phosphorylation and nuclear translocation of PKM2 promotes the Warburg effect. Nat Cell Biol 2012;14:1295-304.
18. Hitosugi T, Fan J, Chung TW, Lythgoe K, Wang X, Xie J, et al. Tyrosine phosphorylation of mitochondrial pyruvate dehydrogenase kinase 1 is important for cancer metabolism. Mol Cell 2011;44:864-77.
19. Kim JW, Tchernyshyov I, Semenza GL, Dang CV. HIF-1-mediated expression of pyruvate dehydrogenase kinase: A metabolic switch required for cellular adaptation to hypoxia. Cell Metab 2006;3: 177-85.
20. Franovic A, Gunaratnam L, Smith K, Robert I, Patten D, Lee S. Translational up-regulation of the EGFR by tumor hypoxia provides a nonmutational explanation for its overexpression in human cancer. Proc Natl Acad Sci U S A 2007;104:13092-7.
21. Mendez O, Zavadil J, Esencay M, Lukyanov Y, Santovasi D, Wang SC, et al. Knock down of HIF-1alpha in glioma cells reduces migration in vitro and invasion in vivo and impairs their ability to form tumor spheres. Mol Cancer 2010;9:133-9.
22. Hofstetter CP, Burkhardt JK, Shin BJ, Gursel DB, Mubita L, Gorrepati R, et al. Protein phosphatase 2A mediates dormancy of glioblastoma multiforme-derived tumor stem-like cells during hypoxia. PLoS ONE 2012;7:e30059.
23. Papandreou I, Cairns RA, Fontana L, Lim AL, Denko NC. HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. Cell Metab 2006;3:187-97.
24. Dasari VR, Velpula KK, Alapati K, Gujrati M, Tsung AJ. Cord blood stem cells inhibit epidermal growth factor receptor translocation to mitochondria in glioblastoma. PLoS ONE 2012;7:e31884.
25. Fantin VR, St-Pierre J, Leder P. Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance. Cancer Cell 2006;9:425-34.
26. Christofk HR, Vander Heiden MG, Harris MH, Ramanathan A, Gerszten RE, Wei R, et al. The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature 2008;452:230-3.
27. Kono SA, Marshall ME, Ware KE, Heasley LE. The fibroblast growth factor receptor signaling pathway as a mediator of intrinsic resistance to EGFR-specific tyrosine kinase inhibitors in non-small cell lung cancer. Drug Resist Updat 2009;12:95-102.
28. Munoz-Pinedo C, El MN, Ricci JE. Cancer metabolism: Current perspectives and future directions. Cell Death Dis 2012;3:e248.
29. Plathow C, Weber WA. Tumor cell metabolism imaging. J Nucl Med 2008;49:43S-63S.
30. Demory ML, Boerner JL, Davidson R, Faust W, Miyake T, Lee I, et al. Epidermal growth factor receptor translocation to the mitochondria: Regulation and effect. J Biol Chem 2009;284:36592-604.
31. Sanchez WY, McGee SL, Connor T, Mottram B, Wilkinson A, Whitehead JP, et al. Dichloroacetate inhibits aerobic glycolysis in multiple myeloma cells and increases sensitivity to bortezomib. Br J Cancer 2013;108:1624-33.
32. Shen YC, Ou DL, Hsu C, Lin KL, Chang CY, Lin CY, et al. Activating oxidative phosphorylation by a pyruvate dehydrogenase kinase inhibitor overcomes sorafenib resistance of hepatocellular carcinoma. Br J Cancer 2013;108:72-81.
33. Shahrzad S, Lacombe K, Adamcic U, Minhas K, Coomber BL. Sodium dichloroacetate (DCA) reduces apoptosis in colorectal tumor hypoxia. Cancer Lett 2010;297:75-83.
34. Michelakis ED, Sutendra G, Dromparis P, Webster L, Haromy A, Niven E, et al. Metabolic modulation of glioblastoma with dichloroacetate. Sci Transl Med 2010;2:31ra34.