Abortive autophagy induces endoplasmic reticulum stress and cell death in cancer cells

Sofie Claerhout, Bhaskar Dutta, Wouter Bossuyt, Fan Zhang, Catherine Nguyen-Charles, Jennifer B. Dennison, Qinghua Yu, Shuangxing Yu, Gábor Balázsi, Yiling Lu, Gordon Mills

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere39400
JournalPLoS One
Volume7
Issue number6
DOIs
StatePublished - Jun 26 2012
Externally publishedYes

Fingerprint

Endoplasmic Reticulum Stress
autophagy
Autophagy
Cell death
endoplasmic reticulum
cell death
Cell Death
Cells
Neoplasms
Tissue
cell lines
Cell Line
Cell signaling
cell communication
neoplasms
Modulators
Small Interfering RNA
small interfering RNA
neoplasm cells
Intercellular Signaling Peptides and Proteins

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Claerhout, S., Dutta, B., Bossuyt, W., Zhang, F., Nguyen-Charles, C., Dennison, J. B., ... Mills, G. (2012). Abortive autophagy induces endoplasmic reticulum stress and cell death in cancer cells. PLoS One, 7(6), [e39400]. https://doi.org/10.1371/journal.pone.0039400

Abortive autophagy induces endoplasmic reticulum stress and cell death in cancer cells. / Claerhout, Sofie; Dutta, Bhaskar; Bossuyt, Wouter; Zhang, Fan; Nguyen-Charles, Catherine; Dennison, Jennifer B.; Yu, Qinghua; Yu, Shuangxing; Balázsi, Gábor; Lu, Yiling; Mills, Gordon.

In: PLoS One, Vol. 7, No. 6, e39400, 26.06.2012.

Research output: Contribution to journalArticle

Claerhout, S, Dutta, B, Bossuyt, W, Zhang, F, Nguyen-Charles, C, Dennison, JB, Yu, Q, Yu, S, Balázsi, G, Lu, Y & Mills, G 2012, 'Abortive autophagy induces endoplasmic reticulum stress and cell death in cancer cells', PLoS One, vol. 7, no. 6, e39400. https://doi.org/10.1371/journal.pone.0039400
Claerhout S, Dutta B, Bossuyt W, Zhang F, Nguyen-Charles C, Dennison JB et al. Abortive autophagy induces endoplasmic reticulum stress and cell death in cancer cells. PLoS One. 2012 Jun 26;7(6). e39400. https://doi.org/10.1371/journal.pone.0039400
Claerhout, Sofie ; Dutta, Bhaskar ; Bossuyt, Wouter ; Zhang, Fan ; Nguyen-Charles, Catherine ; Dennison, Jennifer B. ; Yu, Qinghua ; Yu, Shuangxing ; Balázsi, Gábor ; Lu, Yiling ; Mills, Gordon. / Abortive autophagy induces endoplasmic reticulum stress and cell death in cancer cells. In: PLoS One. 2012 ; Vol. 7, No. 6.
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