Hypoxia-Inducible Factor-1: A Critical Player in the Survival Strategy of Stressed Cells.
Hypoxia-Inducible Factor-1: A Critical Player in the Survival Strategy of Stressed Cells.
复制标题
DOI：
10.1002/jcb.25283
复制
发表时间：
2016-02
影响因子：
4
通讯作者：
Sang N
中科院分区：
文献类型：
--
作者：
Chen S;Sang N
HIF-1 激活已被公认为是缺氧的适应性策略。最近发现，缺氧常常伴随着葡萄糖或氨基酸供应不足，这是循环不良的常见结果，这种情况经常发生在实体瘤和缺血性病变中，从而造成混合营养不足。为了应对营养不足，应激细胞会引发生存策略，包括激活 AMPK 和 HIF-1 以应对应激。特别是，在实体瘤中，HIF-1 促进细胞存活和迁移，刺激血管生成，并诱导对放射和化疗的抵抗。有趣的是，据报道辐射和一些化疗药物会触发 AMPK 的激活。在这里，我们讨论可能将应激反应机制（包括 AMPK 激活、ATF4 激活以及 Hsp70/Hsp90 功能增强与 HIF-1 激活）联系起来的最新进展。将讨论应激促进的 HIF-1 激活在实体瘤和缺血性疾病中的潜在意义和应用。更好地了解暴露于压力的细胞中 HIF-1 的激活有望促进专门调节细胞生存策略的治疗方法的设计。
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.