• 1
    Brown JM,Giaccia AJ. The unique physiology of solid tumors: opportunities (and problems) for cancer therapy. Cancer Res 1998; 58: 140816.
  • 2
    Harris AL. Hypoxia–a key regulatory factor in tumour growth. Nat Rev Cancer 2002; 2: 3847.
  • 3
    Graeber TG,Osmanian C,Jacks T,Housman DE,Koch CJ,Lowe SW,Giaccia AJ. Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours. Nature 1996; 379: 8891.
  • 4
    Hockel M,Vaupel P. Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects. J Natl Cancer Inst 2001; 93: 26676.
  • 5
    Gort EH,Groot AJ,Derks van de Ven TL,van der Groep P,Verlaan I,van Laar T,van Diest PJ,van der Wall E,Shvarts A. Hypoxia-inducible factor-1alpha expression requires PI 3-kinase activity and correlates with Akt1 phosphorylation in invasive breast carcinomas. Oncogene 2006; 25: 61237.
  • 6
    Kwon SJ,Song JJ,Lee YJ. Signal pathway of hypoxia-inducible factor-1alpha phosphorylation and its interaction with von Hippel-Lindau tumor suppressor protein during ischemia in MiaPaCa-2 pancreatic cancer cells. Clin Cancer Res 2005; 11: 760713.
  • 7
    Minet E,Arnould T,Michel G,Roland I,Mottet D,Raes M,Remacle J,Michiels C. ERK activation upon hypoxia: involvement in HIF-1 activation. FEBS Lett 2000; 468: 538.
  • 8
    Mottet D,Dumont V,Deccache Y,Demazy C,Ninane N,Raes M,Michiels C. Regulation of hypoxia-inducible factor-1alpha protein level during hypoxic conditions by the phosphatidylinositol 3-kinase/Akt/glycogen synthase kinase 3beta pathway in HepG2 cells. J Biol Chem 2003; 278: 3127785.
  • 9
    Pore N,Jiang Z,Shu HK,Bernhard E,Kao GD,Maity A. Akt1 activation can augment hypoxia-inducible factor-1alpha expression by increasing protein translation through a mammalian target of rapamycin-independent pathway. Mol Cancer Res 2006; 4: 4719.
  • 10
    Tanaka H,Yamamoto M,Hashimoto N,Miyakoshi M,Tamakawa S,Yoshie M,Tokusashi Y,Yokoyama K,Yaginuma Y,Ogawa K. Hypoxia-independent overexpression of hypoxia-inducible factor 1alpha as an early change in mouse hepatocarcinogenesis. Cancer Res 2006; 66: 1126370.
  • 11
    Koumenis C,Wouters BG. “Translating” tumor hypoxia: unfolded protein response (UPR)-dependent and UPR-independent pathways. Mol Cancer Res 2006; 4: 42336.
  • 12
    Laderoute KR,Amin K,Calaoagan JM,Knapp M,Le T,Orduna J,Foretz M,Viollet B. 5′-AMP-activated protein kinase (AMPK) is induced by low-oxygen and glucose deprivation conditions found in solid-tumor microenvironments. Mol Cell Biol 2006; 26: 533647.
  • 13
    Lum JJ,DeBerardinis RJ,Thompson CB. Autophagy in metazoans: cell survival in the land of plenty. Nat Rev Mol Cell Biol 2005; 6: 43948.
  • 14
    Lluis JM,Buricchi F,Chiarugi P,Morales A,Fernandez-Checa JC. Dual role of mitochondrial reactive oxygen species in hypoxia signaling: activation of nuclear factor-{kappa}B via c-SRC and oxidant-dependent cell death. Cancer Res 2007; 67: 736877.
  • 15
    Gray MJ,Zhang J,Ellis LM,Semenza GL,Evans DB,Watowich SS,Gallick GE. HIF-1alpha. STAT3, CBP/p300 and Ref-1/APE are components of a transcriptional complex that regulates. Src-dependent hypoxia-induced expression of. VEGF in pancreatic and prostate carcinomas. Oncogene 2005; 24: 311020.
  • 16
    Hedley D,Pintilie M,Woo J,Nicklee T,Morrison A,Birle D,Fyles A,Milosevic M,Hill R. Up-regulation of the redox mediators thioredoxin and apurinic/apyrimidinic excision (APE)/Ref-1 in hypoxic microregions of invasive cervical carcinomas, mapped using multispectral, wide-field fluorescence image analysis. Am J Pathol 2004; 164: 55765.
  • 17
    Pham NA,Jacobberger JW,Schimmer AD,Cao P,Gronda M,Hedley DW. The dietary isothiocyanate sulforaphane targets pathways of apoptosis, cell cycle arrest, and oxidative stress in human pancreatic cancer cells and inhibits tumor growth in severe combined immunodeficient mice. Mol Cancer Ther 2004; 3: 123948.
  • 18
    Cairns RA,Hill RP. Acute hypoxia enhances spontaneous lymph node metastasis in an orthotopic murine model of human cervical carcinoma. Cancer Res 2004; 64: 205461.
  • 19
    Kavanagh MC,Tsang V,Chow S,Koch C,Hedley D,Minkin S,Hill RP. A comparison in individual murine tumors of techniques for measuring oxygen levels. Int J Radiat Oncol Biol Phys 1999; 44: 113746.
  • 20
    Cairns RA,Kalliomaki T,Hill RP. Acute (cyclic) hypoxia enhances spontaneous metastasis of KHT murine tumors. Cancer Res 2001; 61: 89038.
  • 21
    Vukovic V,Nicklee T,Hedley DW. Differential effects of buthionine sulphoximine in hypoxic and non-hypoxic regions of human cervical carcinoma xenografts. Radiother Oncol 2001; 60: 6973.
  • 22
    Birle DC,Hedley DW. Signaling interactions of rapamycin combined with erlotinib in cervical carcinoma xenografts. Mol Cancer Ther 2006; 5: 2494502.
  • 23
    Birle DC,Hedley DW. Suppression of the hypoxia-inducible factor-1 response in cervical carcinoma xenografts by proteasome inhibitors. Cancer Res 2007; 67: 173543.
  • 24
    Dehm SM,Bonham K. SRC gene expression in human cancer: the role of transcriptional activation. Biochem Cell Biol 2004; 82: 26374.
  • 25
    Kim MS,Kwon HJ,Lee YM,Baek JH,Jang JE,Lee SW,Moon EJ,Kim HS,Lee SK,Chung HY,Kim CW,Kim KW. Histone deacetylases induce angiogenesis by negative regulation of tumor suppressor genes. Nat Med 2001; 7: 43743.
  • 26
    Ardyanto TD,Osaki M,Nagahama Y,Yamaga K,Maeta N,Tamura T,Ito H. Down-regulation of cobalt-induced HIF-1alpha expression correlates with cell proliferation and apoptosis in human gastric carcinoma cells. Oncol Rep 2008; 19: 33943.
  • 27
    Postovit LM,Abbott DE,Payne SL,Wheaton WW,Margaryan NV,Sullivan R,Jansen MK,Csiszar K,Hendrix MJ,Kirschmann DA. Hypoxia/reoxygenation: a dynamic regulator of lysyl oxidase-facilitated breast cancer migration. J Cell Biochem 2008; 103: 136978.
  • 28
    Xu Q,Briggs J,Park S,Niu G,Kortylewski M,Zhang S,Gritsko T,Turkson J,Kay H,Semenza GL,Cheng JQ,Jove R, et al. Targeting Stat3 blocks both HIF-1 and VEGF expression induced by multiple oncogenic growth signaling pathways. Oncogene 2005; 24: 555260.
  • 29
    Lee MY,Joung YH,Lim EJ,Park JH,Ye SK,Park T,Zhang Z,Park DK,Lee KJ,Yang YM. Phosphorylation and activation of STAT proteins by hypoxia in breast cancer cells. Breast 2006; 15: 18795.
  • 30
    Yang XP,Irani K,Mattagajasingh S,Dipaula A,Khanday F,Ozaki M,Fox-Talbot K,Baldwin WM,III,Becker LC. Signal transducer and activator of transcription 3alpha and specificity protein 1 interact to upregulate intercellular adhesion molecule-1 in ischemic-reperfused myocardium and vascular endothelium. Arterioscler Thromb Vasc Biol 2005; 25: 1395400.
  • 31
    Hiscox S,Jordan NJ,Morgan L,Green TP,Nicholson RI. Src kinase promotes adhesion-independent activation of FAK and enhances cellular migration in tamoxifen-resistant breast cancer cells. Clin Exp Metastasis 2007; 24: 15767.