HIF-1: Using two hands to flip the angiogenic switch

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195 Scopus citations


In brain, breast, and other common human tumors there is a correlation between expression of the transcriptional activator hypoxia-inducible factor 1 (HIF-1) and tumor grade and vascularization. HIF-1 stimulates angiogenesis by activating transcription of the gene encoding vascular endothelial growth factor (VEGF). HIF-1 is a heterodimer consisting of a constitutively-expressed HIF-1β subunit and an O2- and growth factor-regulated HIF-1α subunit. Recent studies have demonstrated that HIF-1α expression is increased in tumor relative to normal tissue by two mechanisms. First, decreased intratumoral O2 concentrations provide a physiological stimulus. Second, genetic alterations that activate oncogene products or inactivate tumor suppressor gene products increase HIF-1α expression and/or HIF-1 transcriptional activity independent of the O2 concentration. Taken together, these recent data suggest that increased HIF-1 activity provides a molecular basis for VEGF-induced angiogenesis and other adaptations of cancer cells to hypoxia that are critical for establishment of a primary tumor and its progression to the lethal phenotype.

Original languageEnglish (US)
Pages (from-to)59-65
Number of pages7
JournalCancer and Metastasis Reviews
Issue number1-2
StatePublished - 2000


  • AKT
  • MAP kinase
  • P53
  • PTEN
  • Phosphatidylinositol-3-kinase
  • SRC
  • Vascular endothelial growth factor
  • Von Hippel-Lindau protein

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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