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Curr Opin Cell Biol. 2011 Apr;23(2):150-6. doi: 10.1016/ Epub 2010 Oct 21.

The critical role of GRP78 in physiologic and pathologic stress.

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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.


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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