Hypoxia-inducible factor 1 and cancer pathogenesis.
Hypoxia-inducible factor 1 (HIF-1) is a transcriptional activator that mediates adaptive responses to hypoxia. HIF-1 activity is increased in the majority of human cancers as a result of genetic alterations and intratumoral hypoxia. HIF-1 activates the transcription of genes that increase O(2) availability by stimulating angiogenesis or that reprogram cellular metabolism to adapt to reduced O(2) availability. Proof of principle studies in mouse models suggests that inhibition of HIF-1 activity may have therapeutic effects, especially in combination with other anticancer drugs.
Semenza
Gregg L
GL
Vascular Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. gsemenza@jhmi.edu
D000818:Animals; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism; D004734:Energy Metabolism; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D010100:Oxygen / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics / Q000378:metabolism
D051793:Hypoxia-Inducible Factor 1; D016271:Proto-Oncogene Proteins c-myc; D017382:Reactive Oxygen Species; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human; D005947:Glucose; D010100:Oxygen