Lauzier Marie-Claude, Michaud Maude D, Déry Marc-André C, Richard Darren E
Centre de recherche de l'Hôtel-Dieu de Québec, Département de médecine, Université Laval, 10 rue McMahon, QC, Canada G1R 2J6.
Bull Cancer. 2006 Apr;93(4):349-56.
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.
转录因子缺氧诱导因子1（HIF-1）可响应缺氧应激调节70多个基因的表达。HIF-1由两个亚基组成，其活性受HIF-1α蛋白亚基可用性的调节。这种极不稳定的蛋白质的稳定性和转录活性受翻译后修饰的影响。缺氧和非缺氧刺激可在多种人类癌症中促使活性HIF-1复合物形成。然而，HIF-1激活在肿瘤进展中的确切意义仍未完全明确。HIF-1依赖性基因产物参与肿瘤血管生成、向无氧糖酵解的代谢转换以及促生存、增殖和凋亡机制。在本综述中，我们将聚焦于导致HIF-1激活的缺氧和非缺氧刺激及其在肿瘤进程中的意义。我们将重点介绍HIF-1上下游分子和细胞信号传导的最新进展。
