title: Hypoxia-Inducible Factor-1: A Critical Player in the Survival Strategy of Stressed Cells.
abstract: HIF-1 activation has been well known as an adaptive strategy to hypoxia. Recently it became clear that hypoxia was often accompanied by insufficient supply of glucose or amino acids as a common result of poor circulation that frequently occurs in solid tumors and ischemic lesions, creating a mixed nutrient insufficiency. In response to nutrient insufficiency, stressed cells elicit survival strategies including activation of AMPK and HIF-1 to cope with the stress. Particularly, in solid tumors, HIF-1 promotes cell survival and migration, stimulates angiogenesis, and induces resistance to radiation and chemotherapy. Interestingly, radiation and some chemotherapeutics are reported to trigger the activation of AMPK. Here we discuss the recent advances that may potentially link the stress responsive mechanisms including AMPK activation, ATF4 activation and the enhancement of Hsp70/Hsp90 function to HIF-1 activation. Potential implication and application of the stress-facilitated HIF-1 activation in solid tumors and ischemic disorders will be discussed. A better understanding of HIF-1 activation in cells exposed to stresses is expected to facilitate the design of therapeutic approaches that specifically modulate cell survival strategy.
authors.affiliation: Department of Biology and Graduate Program of Biological Sciences, College of Arts and Sciences, Drexel University, Philadelphia, Pennsylvania.
authors.forename: Shuyang
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Biology and Graduate Program of Biological Sciences, College of Arts and Sciences, Drexel University, Philadelphia, Pennsylvania.|Department of Pathology and Laboratory Medicine, Drexel University College of Medicine, Philadelphia, Pennsylvania.|Sydney Kimmel Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Nianli
authors.initials: N
authors.lastname: Sang
mesh_terms: D000107:Acetylation; D000818:Animals; D015687:Cell Hypoxia; D006655:Histone Deacetylases / Q000502:physiology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology*; D007511:Ischemia / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D013312:Stress, Physiological; D015533:Transcriptional Activation
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D006655:Histone Deacetylases
keywords: AMPK; HDAC4; HDAC5; HIF-1; HYPOXIA; Hsp70; Hsp90; STRESS RESPONSE