Hypoxia, clonal selection, and the role of HIF-1 in tumor progression

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519 Scopus citations


Tumor progression occurs as a result of the clonal selection of cells in which somatic mutations have activated oncogenes or inactivated tumor suppressor genes leading to increased proliferation and/or survival within the hypoxic tumor microenvironment. Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that mediates adaptive responses to reduced O2 availability, including angiogenesis and glycolysis. Expression of the O2- regulated HIF-1α subunit and HIF-1 transcriptional activity are increased dramatically in hypoxic cells. Recent studies indicate that many common tumor-specific genetic alterations also lead to increased HIF-1α expression and/or activity. Thus, genetic and physiologic alterations within tumors act synergistically to increase HIF-1 transcriptional activity, which appears to play a critical role in the development of invasive and metastatic properties that define the lethal cancer phenotype.

Original languageEnglish (US)
Pages (from-to)71-103
Number of pages33
JournalCritical reviews in biochemistry and molecular biology
Issue number2
StatePublished - 2000


  • Angiogenesis
  • Cancer
  • Glycolysis p53
  • Ras
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology


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