ER stress and cancer.

摘要

Due to inadequate vascularizarion and rapid growth, tumor cells experience hypoxia and receive reduced amounts of nutrients including both amino acids and glucose. Inadequate supplies of glucose affect the glycosylation of secretory pathway proteins and ATP production, both of which lead to the accumulation of unfolded proteins in the endoplasmic reticulum (ER), resulting in ER stress. This activates a cytoprotective signal transduction pathway known as die "unfolded protein response" or UPR. A number of studies point to UPR activation in a variety of tumor types. Most significantly, several recent studies have demonstrated that interfering with the activation of different arms of the UPR or altering the levels of the ER molecular chaperone GRP78/BiP, a master regulator of ER function and die UPR, can inhibit tumor growth in vivo, arguing that not only is the UPR activated in tumors but that it contributes to survival or growth of the cancer cells. The hypoxia and the unfolded protein responses are often studied separately in cultured cells and in in vivo model systems, even though some common elements exist in the two pathways and that there might be synergy in the activation of some downstream effects when both pathways are activated simultaneously in a tumor. The reviews in this issue were assembled to provide an overview of these important issues in the development, survival and metastasis of cancer cells. Amy S-Lee; Undo M. Hendershot; Deportment of Biochemist ond Molaulor Biology; USC/Norris Comprehensive Cancer Center; University of Souihem California Keck School of Medicine; Los Angeles, California USA