Differential effects of endoplasmic reticulum stress-induced autophagy on cell survival.

Abstract

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.

• Authors: Wen-Xing Ding, Hong-Min Ni, Wentao Gao, Yi-Feng Hou, Melissa A Melan, Xiaoyun Chen, Donna B Stolz, Zhi-Ming Shao, Xiao-Ming Yin
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 282 Issue 7 Pg. 4702-4710 (Feb 16 2007) ISSN: 0021-9258 [Print] United States
• PMID: 17135238 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Ubiquitin

Topics

• Animals
• Antineoplastic Agents (pharmacology, therapeutic use)
• Autophagy (drug effects)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Colonic Neoplasms (drug therapy, metabolism, ultrastructure)
• Endoplasmic Reticulum (metabolism, ultrastructure)
• Fibroblasts (metabolism, ultrastructure)
• Humans
• Male
• Mice
• Prostatic Neoplasms (drug therapy, metabolism, ultrastructure)
• Stress, Physiological
• Ubiquitin (metabolism)
• Vacuoles (metabolism, ultrastructure)