HIF1α and HIF2α: sibling rivalry in hypoxic tumour growth and progression

Nat Rev Cancer. 2011 Dec 15;12(1):9-22. doi: 10.1038/nrc3183.


Hypoxia-inducible factors (HIFs) are broadly expressed in human cancers, and HIF1α and HIF2α were previously suspected to promote tumour progression through largely overlapping functions. However, this relatively simple model has now been challenged in light of recent data from various approaches that reveal unique and sometimes opposing activities of these HIFα isoforms in both normal physiology and disease. These effects are mediated in part through the regulation of unique target genes, as well as through direct and indirect interactions with important oncoproteins and tumour suppressors, including MYC and p53. As HIF inhibitors are currently undergoing clinical evaluation as cancer therapeutics, a more thorough understanding of the unique roles performed by HIF1α and HIF2α in human neoplasia is warranted.

Publication types

  • Review

MeSH terms

  • Acetylation
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / physiology*
  • Cell Hypoxia
  • Cell Proliferation
  • Disease Progression
  • Gene Expression Regulation
  • Genes, myc
  • Genes, p53
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / physiology*
  • Mechanistic Target of Rapamycin Complex 1
  • Multiprotein Complexes
  • Neoplasms / pathology*
  • Protein Processing, Post-Translational
  • Proteins / physiology
  • TOR Serine-Threonine Kinases


  • Basic Helix-Loop-Helix Transcription Factors
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Multiprotein Complexes
  • Proteins
  • endothelial PAS domain-containing protein 1
  • Mechanistic Target of Rapamycin Complex 1
  • TOR Serine-Threonine Kinases