title: Abortive autophagy induces endoplasmic reticulum stress and cell death in cancer cells.
abstract: Autophagic cell death or abortive autophagy has been proposed to eliminate damaged as well as cancer cells, but there remains a critical gap in our knowledge in how this process is regulated. The goal of this study was to identify modulators of the autophagic cell death pathway and elucidate their effects on cellular signaling and function. The result of our siRNA library screenings show that an intact coatomer complex I (COPI) is obligatory for productive autophagy. Depletion of COPI complex members decreased cell survival and impaired productive autophagy which preceded endoplasmic reticulum stress. Further, abortive autophagy provoked by COPI depletion significantly altered growth factor signaling in multiple cancer cell lines. Finally, we show that COPI complex members are overexpressed in an array of cancer cell lines and several types of cancer tissues as compared to normal cell lines or tissues. In cancer tissues, overexpression of COPI members is associated with poor prognosis. Our results demonstrate that the coatomer complex is essential for productive autophagy and cellular survival, and thus inhibition of COPI members may promote cell death of cancer cells when apoptosis is compromised.
authors: Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America. SAClaerhout@mdanderson.org
authors: Sofie
authors: S
authors: Claerhout
authors: Bhaskar
authors: B
authors: Dutta
authors: Wouter
authors: W
authors: Bossuyt
authors: Fan
authors: F
authors: Zhang
authors: Catherine
authors: C
authors: Nguyen-Charles
authors: Jennifer B
authors: JB
authors: Dennison
authors: Qinghua
authors: Q
authors: Yu
authors: Shuangxing
authors: S
authors: Yu
authors: Gábor
authors: G
authors: Balázsi
authors: Yiling
authors: Y
authors: Lu
authors: Gordon B
authors: GB
authors: Mills
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D001343:Autophagy / Q000235:genetics / Q000502:physiology*; D015153:Blotting, Western; D016923:Cell Death / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D004591:Electrophoresis, Polyacrylamide Gel; D059865:Endoplasmic Reticulum Stress / Q000235:genetics / Q000502:physiology*; D005260:Female; D006801:Humans; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D034741:RNA, Small Interfering
chemical_list: D034741:RNA, Small Interfering