HIF-1 and tumor progression: pathophysiology and therapeutics.
Hypoxia-inducible factor 1 (HIF-1) controls oxygen delivery (via angiogenesis) and metabolic adaptation to hypoxia (via glycolysis). HIF-1 consists of a constitutively expressed HIF-1 beta subunit and an oxygen- and growth-factor-regulated HIF-1 alpha subunit. In xenografts, tumor growth and angiogenesis are correlated with HIF-1 expression. In human cancers, HIF-1 alpha is overexpressed as a result of intratumoral hypoxia and genetic alterations affecting key oncogenes and tumor suppressor genes. HIF-1 alpha overexpression in biopsies of brain, breast, cervical, esophageal, oropharyngeal and ovarian cancers is correlated with treatment failure and mortality. Increased HIF-1 activity promotes tumor progression, and inhibition of HIF-1 could represent a novel approach to cancer therapy.
Semenza
Gregg L
GL
Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, 600 N. Wolfe Street, CMSC-1004, Baltimore, MD 21287-3914, USA. gsemenza@jhmi.edu
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015687:Cell Hypoxia; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D018450:Disease Progression; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009369:Neoplasms / Q000098:blood supply / Q000503:physiopathology* / Q000628:therapy; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D014157:Transcription Factors; D010100:Oxygen