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 B. Mills

    Research output: Contribution to journalArticle

    19 Scopus citations

    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

    ASJC Scopus subject areas

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

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    Claerhout, S., Dutta, B., Bossuyt, W., Zhang, F., Nguyen-Charles, C., Dennison, J. B., Yu, Q., Yu, S., Balázsi, G., Lu, Y., & Mills, G. B. (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