The critical role of GRP78 in physiologic and pathologic stress.

The critical role of GRP78 in physiologic and pathologic stress.
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DOI:
10.1016/j.ceb.2010.09.007
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发表时间:
2011-04
影响因子:
7.5
通讯作者:
Lee AS
Lee AS
中科院分区:
生物学2区
文献类型:
--
作者:
Pfaffenbach KT;Lee AS

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GRP78 是主要的内质网伴侣,也是未折叠蛋白反应的主要调节因子。除了在早期胚胎发育中发挥重要作用外,最近的研究还特别表明 GRP78 和伴侣完整性在衰老过程和年龄相关疾病中的作用。另一个令人兴奋的发现是胰岛素/IGF-1 信号通路对 GRP78 的调节影响细胞增殖和存活。小鼠癌症模型与细胞培养研究相结合,验证了 GRP78 在肿瘤发生和肿瘤血管生成中的关键作用。此外,这些研究证明了 GRP78 抑制致癌 PI3K/AKT 信号传导的能力。在癌细胞和经历内质网应激的细胞中,细胞表面 GRP78 的发现提出了一种新的治疗策略。
GRP78 is a major endoplasmic reticulum chaperone as well as a master regulator of the unfolded protein response. In addition to playing an essential role in early embryonic development, recent studies have emerged specifically implicating GRP78 and chaperone integrity in the aging process and age-related diseases. Another exciting discovery is the regulation of GRP78 by insulin/IGF-1 signaling pathways impacting cell proliferation and survival. Mouse models of cancer, in combination with cell culture studies, validate the critical role of GRP78 in tumorigenesis and tumor angiogenesis. Further, these studies demonstrate the ability of GRP78 to suppress oncogenic PI3K/AKT signaling. The discovery of cell surface GRP78, in cancer cells and cells undergoing ER stress, presents a novel therapeutic strategy.
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