title: HIF1α and HIF2α: sibling rivalry in hypoxic tumour growth and progression.
abstract: 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.
authors.affiliation: Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Keith
authors.forename: Randall S
authors.initials: RS
authors.lastname: Johnson
authors.forename: M Celeste
authors.initials: MC
authors.lastname: Simon
mesh_terms: D000107:Acetylation; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology*; D015687:Cell Hypoxia; D049109:Cell Proliferation; D018450:Disease Progression; D005786:Gene Expression Regulation; D016259:Genes, myc; D016158:Genes, p53; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology*; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D009369:Neoplasms / Q000473:pathology*; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000502:physiology; D058570:TOR Serine-Threonine Kinases; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D011506:Proteins; D058570:TOR Serine-Threonine Kinases; D000099162:Endothelial PAS Domain-Containing Protein 1