[HIF-1 activation during tumor progression: implications and consequences].
The transcription factor hypoxia-inducible factor 1 (HIF-1) regulates the expression of more than 70 genes in response to hypoxic stress. Composed of two subunits, HIF-1 activity is modulated by the availability of the HIF-1alpha protein subunit. The stability and transcriptional activity of this extremely labile protein is affected by post-translational modifications. Hypoxia and non-hypoxic stimuli allow the formation of an active HIF-1 complex in many types of human cancers. However, the exact implication of HIF-1 activation in tumor progression is still not precisely understood. The HIF-1 dependent genic products are involved in tumoral angiogenesis, in the metabolic switch to anaerobic glycolysis and in prosurvival, proliferative and apoptotic mechanisms. In this review, we will focus on the hypoxic and non-hypoxic stimuli leading to HIF-1 activation and in its implication in tumor processes. We will highlight the most recent developments in molecular and cellular signaling that are upstream and downstream of HIF-1.
Lauzier
Marie-Claude
MC
Centre de recherche de l'Hôtel-Dieu de Québec, Département de médecine, Université Laval, 10 rue McMahon, QC, Canada G1R 2J6.
Michaud
Maude D
MD
Déry
Marc-André C
MA
Richard
Darren E
DE
D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000235:genetics* / Q000378:metabolism; D015687:Cell Hypoxia; D018450:Disease Progression; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism*; D009369:Neoplasms / Q000503:physiopathology*; D010101:Oxygen Consumption; D014158:Transcription, Genetic
C497396:ARNT protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator