Cancer therapy by targeting hypoxia-inducible factor-1.
Tumors are invariably less well-oxygenated than the normal tissues from which they arose. Hypoxia-inducible factor-1 (HIF-1), a key transcriptional regulator, plays a central role in the adaptation of tumor cells to hypoxia by activating the transcription of genes, which regulate several biological processes including angiogenesis, cell proliferation, survival, glucose metabolism and migration. The expression, activity and stability of HIF-1 is not only induced in response to reduced oxygen availability but also modulated through PI-3K, MAPK, autocrine signaling pathways, E3 ubiquitin ligases, and other regulators. The regulators and effects of HIF-1 in cancer have intensively provided us a new clue for the HIF-1 targeting anticancer therapy. This review evaluates the HIF-1 structure, the regulation mechanisms, the functions in cancer and corresponding anticancer strategies.
Li
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Department of Pathophysiology, Tongji Medical College of Huazhong University of Science & Technology, Hangkong Road No.13, Wuhan 430030, China.
Ye
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D000818:Animals; D015687:Cell Hypoxia; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000378:metabolism* / Q000628:therapy; D054730:Protein Interaction Domains and Motifs; D015398:Signal Transduction / Q000187:drug effects
D051793:Hypoxia-Inducible Factor 1