Differential effects of endoplasmic reticulum stress-induced autophagy on cell survival.
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.
Ding
Wen-Xing
WX
Departments of University of Pittsburgh School of Medicine, Pennsylvania 15261.
Ni
Hong-Min
HM
Departments of University of Pittsburgh School of Medicine, Pennsylvania 15261.
Gao
Wentao
W
Departments of University of Pittsburgh School of Medicine, Pennsylvania 15261.
Hou
Yi-Feng
YF
Departments of University of Pittsburgh School of Medicine, Pennsylvania 15261; Department of Surgery, Cancer Hospital, Fudan University, Shanghai 200032, China.
Melan
Melissa A
MA
Departments of University of Pittsburgh School of Medicine, Pennsylvania 15261.
Chen
Xiaoyun
X
Departments of University of Pittsburgh School of Medicine, Pennsylvania 15261.
Stolz
Donna B
DB
Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pennsylvania 15261 and the.
Shao
Zhi-Ming
ZM
Department of Surgery, Cancer Hospital, Fudan University, Shanghai 200032, China.
Yin
Xiao-Ming
XM
Departments of University of Pittsburgh School of Medicine, Pennsylvania 15261; Pathology and University of Pittsburgh School of Medicine, Pennsylvania 15261. Electronic address: xmyin@pitt.edu.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001343:Autophagy / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000648:ultrastructure; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000648:ultrastructure; D005347:Fibroblasts / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000648:ultrastructure; D013312:Stress, Physiological; D025801:Ubiquitin / Q000378:metabolism*; D014617:Vacuoles / Q000378:metabolism* / Q000648:ultrastructure
D000970:Antineoplastic Agents; D025801:Ubiquitin