Differential Effects of Endoplasmic Reticulum Stress-induced Autophagy on Cell Survival

• Published in: The Journal of biological chemistry Vol. 282; no. 7; pp. 4702 - 4710
• Main Authors: Ding, Wen-Xing, Ni, Hong-Min, Gao, Wentao, Hou, Yi-Feng, Melan, Melissa A., Chen, Xiaoyun, Stolz, Donna B., Shao, Zhi-Ming, Yin, Xiao-Ming
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16.02.2007; American Society for Biochemistry and Molecular Biology
• Subjects: Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Autophagy - drug effects; Cell Line, Tumor; Cell Survival - drug effects; Colonic Neoplasms - drug therapy; Colonic Neoplasms - metabolism; Colonic Neoplasms - ultrastructure; Endoplasmic Reticulum - metabolism; Endoplasmic Reticulum - ultrastructure; Fibroblasts - metabolism; Fibroblasts - ultrastructure; Humans; Male; Mice; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - ultrastructure; Stress, Physiological; Ubiquitin - metabolism; Vacuoles - metabolism; Vacuoles - ultrastructure
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M609267200

Autophagy is a cellular response to adverse environment and stress, but its significance in cell survival is not always clear. Here we show that autophagy could be induced in the mammalian cells by chemicals, such as A23187, tunicamycin, thapsigargin, and brefeldin A, that cause endoplasmic reticulum stress. Endoplasmic reticulum stress-induced autophagy is important for clearing polyubiquitinated protein aggregates and for reducing cellular vacuolization in HCT116 colon cancer cells and DU145 prostate cancer cells, thus mitigating endoplasmic reticulum stress and protecting against cell death. In contrast, autophagy induced by the same chemicals does not confer protection in a normal human colon cell line and in the non-transformed murine embryonic fibroblasts but rather contributes to cell death. Thus the impact of autophagy on cell survival during endoplasmic reticulum stress is likely contingent on the status of cells, which could be explored for tumor-specific therapy.