Department of Biochemistry and Molecular Biology, University of Southern California Keck School of Medicine, USC Norris Comprehensive Cancer Center, 1441 Eastlake Avenue, Los Angeles, CA 90089-9176, USA.
Curr Opin Cell Biol. 2011 Apr;23(2):150-6. doi: 10.1016/j.ceb.2010.09.007. Epub 2010 Oct 21.
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.
GRP78 是内质网的主要伴侣蛋白，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，最近的研究特别表明 GRP78 和伴侣蛋白的完整性与衰老过程和与年龄相关的疾病有关。另一个令人兴奋的发现是胰岛素/IGF-1 信号通路对细胞增殖和存活的调节作用。癌症的小鼠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，这些研究表明 GRP78 能够抑制致癌的 PI3K/AKT 信号。在癌细胞和经历内质网应激的细胞中发现细胞表面 GRP78，为一种新的治疗策略提供了依据。
