Mutations in the PI3K/PTEN/TSC2 pathway contribute to mammalian target of rapamycin activity and increased translation under hypoxic conditions

Cancer Research

Volumn 66, Issue 3, 2006, Pages 1561-1569

  Kaper, Fiona ^a   Dornhoefer, Nadja ^a,b   Giaccia, Amato J ^a  

^a STANFORD UNIVERSITY   (United States)

^b UNIVERSITY OF LEIPZIG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

MAMMALIAN TARGET OF RAPAMYCIN; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; TUBERIN;

ARTICLE; CELL DEATH; CELL PROLIFERATION; CELL SURVIVAL; CONTROLLED STUDY; ENZYME ACTIVITY; ENZYME INHIBITION; GENE MUTATION; HUMAN; HUMAN CELL; HYPOXIA; MALE; PRIORITY JOURNAL; PROTEIN SYNTHESIS; PROTEIN SYNTHESIS INHIBITION; RNA TRANSLATION; TUMOR GROWTH; WILD TYPE;

1-PHOSPHATIDYLINOSITOL 3-KINASE; CELL GROWTH PROCESSES; CELL HYPOXIA; CELL LINE, TUMOR; GLIOBLASTOMA; HUMANS; MALE; MUTATION; OXYGEN; PROSTATIC NEOPLASMS; PROTEIN BIOSYNTHESIS; PROTEIN KINASES; PTEN PHOSPHOHYDROLASE; RNA, MESSENGER; SIGNAL TRANSDUCTION; TRANSCRIPTION, GENETIC; TUMOR SUPPRESSOR PROTEINS;

EID: 32944456143     PISSN: 00085472     EISSN: None     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-05-3375     Document Type: Article

References (38)

1. Hoeckel M, Vaupel P. Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects. J Natl Cancer Inst 2001;93:266-76.
2. Semenza GL. Targeting HIF-1 for cancer therapy. Nat Rev Cancer 2003;3:721-32.
3. Pettersen E, Juul N, Ronning O. Regulation of protein metabolism of human cells during and after acute hypoxia. Cancer Res 1986;46:4346-51.
4. Koumenis C, Naczki C, Koritzinsky M, et al. Regulation of protein synthesis by hypoxia via activation of the endoplasmic reticulum kinase PERK and phosphorylation of the translation initiation factor eIF2α. Mol Cell Biol 2002;22:7405-16.
5. Gingras AC, Raught B, Sonenberg N. Regulation of translation initiation by FRAP/mTOR. Genes Dev 2001;15:807-26.
6. Tinton SA, Buc-Calderon PM. Hypoxia increases the association of 4E-binding protein 1 with the initiation factor 4E in isolated rat hepatocytes. FEBS Lett 1999;446:55-9.
7. Arsham AM, Howell JJ, Simon MC. A novel hypoxia-inducible factor-independent hypoxic response regulating mammalian target of rapamycin and its targets. J Biol Chem 2003;278:29655-60.
8. Hay N, Sonenberg N. Upstream and downstream of mTOR. Genes Dev 2004;18:1926-45.
9. Kunz J, Henriquez R, Schneider U, et al. Target of rapamycin in yeast, TOR2, is an essential phosphatidylinositol kinase homolog required for G1 progression. Cell 1993;73:585-96.
10. Sabatini DM, Erdjument-Bromage H, Lui M, et al. RAFT1: a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs. Cell 1994;78:35-43.
11. Zhong H, Chiles K. Feldser D, et al. Modulation of hypoxia-inducible factor 1α expression by the epidermal growth factor/phosphatidylinositol 3-kinase/PTEN/AKT/FRAP pathway in human prostate cancer cells: implications for tumor angiogenesis and therapeutics. Cancer Res 2000;60:1541-5.
12. Hudson CC, Liu M, Chiang GG, et al. Regulation of hypoxia-inducible factor 1α expression and function by the mammalian target of rapamycin. Mol Cell Biol 2002;22:7004-14.
13. Chung J, Grammer TC, Lemon KP, et al. PDGF-and insulin-dependent pp70S6k activation mediated by phosphatidylinositol-3-OH kinase. Nature 1994;370:71-5.
14. Sekulic A, Hudson CC, Homme JL, et al. A direct linkage between the phosphoinositide 3-kinase-AKT signaling pathway and the mammalian target of rapamycin in mitogen-stimulated and transformed cells. Cancer Res 2000;60:3504-13.
15. Neshat MS, Mellinghoff IK, Tran C, et al. Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR Proc Natl Acad Sci U S A 2001;98:10314-9.
16. Inoki K, Li Y, Zhu T, et al. TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat Cell Biol 2002;4:648-57.
17. Garami A, Zwartkruis FJ, Nobukuni T, et al. Insulin activation of Rheb, a mediator of mTOR/S6K/4E-BP signaling, is inhibited by TSC1 and 2. Mol Cell 2003;11:1457-66.
18. Li Y, Inoki K, Guan KL. Biochemical and functional characterizations of small GTPase Rheb and TSC2 GAP activity. Mol Cell Biol 2004;24:7965-75.
19. Inoki K, Li Y, Xu T, et al. Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling. Genes Dev 2003;17:1829-34.
20. Brugarolas J, Lei K, Hurley RL, et al. Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex. Genes Dev 2004;18:2893-904.
21. Schwarzer R, Tondera D, Arnold W, et al. REDD1 integrates hypoxia-mediated survival signaling downstream of phosphatidylinositol 3-kinase. Oncogene 2005;24:1138-49.
22. Vivanco I, Sawyers CL. The phosphatidylinositol 3-kinase AKT pathway in human cancer. Nat Rev Cancer 2002;2:489-501.
23. Ma L, Chen Z, Erdjument-Bromage H, et al. Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis. Cell 2005;121:179-93.
24. Mazure NM, Chen EY, Laderoute KR, et al. Induction of vascular endothelial growth factor by hypoxia is modulated by a phosphatidylinositol 3-kinase/Akt signaling pathway in Ha-ras-transformed cells through a hypoxia inducible factor-1 transcriptional element. Blood 1997;90:3322-31.
25. Zundel W, Schindler C, Haas-Kogan D, et al. Loss of PTEN facilitates HIF-1-mediated gene expression. Genes Dev 2000;14:391-6.
26. Radu A, Neubauer V, Akagi T, et al. PTEN induces cell cycle arrest by decreasing the level and nuclear localization of cyclin D1. Mol Cell Biol 2003;23:6139-49.
27. El-Hashemite N, Walker V, Zhang H, et al. Loss of Tsc1 or Tsc2 induces vascular endothelial growth factor production through mammalian target of rapamycin. Cancer Res 2003;63:5173-7.
28. Sansal I, Sellers WR. The biology and clinical relevance of the PTEN tumor suppressor pathway. J Clin Oncol 2004;22:2954-63.
29. Brugarolas JB, Vazquez F, Reddy A, et al. TSC2 regulates VEGF through mTOR-dependent and -independent pathways. Cancer Cell 2003;4:147-58.
30. Graeber TG, Peterson JF, Tsai M, et al. Hypoxia induces accumulation of p53 protein, but activation of a G1-phase checkpoint by low-oxygen conditions is independent of p53 status. Mol Cell Biol 1994;14:6264-77.
31. Green SL, Giaccia AJ. Tumor hypoxia and the cell cycle: implications for malignant progression and response to therapy. Cancer J Sci Am 1998;4:218-23.
32. Hammond EM, Denko NC, Dorie MJ, et al. Hypoxia links ATR and p53 through replication arrest. Mol Cell Biol 2002;22:1834-43.
33. Heitman J, Movva NK, Hall MN. Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast Science 1991;253:905-9.
34. Lord EM, Harwell L, Koch CJ. Detection of hypoxic cells by monoclonal antibody recognizing 2-nitroimidazole adducts. Cancer Res 1993;53:5721-6.
35. Coutant A, Rescan C, Gilot D, et al. PI3K-FRAP/mTOR pathway is critical for hepatocyte proliferation whereas MEK/ERK supports both proliferation and survival. Hepatology 2002;36:1079-88.
36. Gao N, Flynn DC, Zhang Z, et al. G1 cell cycle progression and the expression of G1 cyclins are regulated by PI3K/AKT/mTOR/p70S6K1 signaling in human ovarian cancer cells. Am J Physiol Cell Physiol 2004;287:C281-91.
37. Gao N, Zhang Z, Jiang BH, et al. Role of PI3K/AKT/mTOR signaling in the cell cycle progression of human prostate cancer. Biochem Biophys Res Commun 2003;310:1124-32.
38. Brown JM. Tumor microenvironment and the response to anticancer therapy. Cancer Biol Ther 2002;1:453-8.