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TRAIL promotes membrane blebbing, detachment and migration of cells displaying a dysfunctional intrinsic pathway of apoptosis

Somasekharan, Syam ; Koc, Michal ; Morizot, Alexandre ; Micheau, Olivier ; Sorensen, Poul ; Gaide, Olivier ; Andera, Ladislav ; Martinou, Jean-Claude

In: Apoptosis, 2013, vol. 18, no. 3, p. 324-336

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    Title
    • TRAIL promotes membrane blebbing, detachment and migration of cells displaying a dysfunctional intrinsic pathway of apoptosis
    Author
    • Somasekharan, Syam. Department of Cell Biology, University of Geneva, Sciences III, 30 quai Ernest Ansermet, 1211, Geneva 4, Switzerland
    • Koc, Michal. Institute of Molecular Genetics, Czech Academy of Sciences, Prague, Czech Republic
    • Morizot, Alexandre. INSERM, UMR866, 21079, Dijon, France
    • Micheau, Olivier. INSERM, UMR866, 21079, Dijon, France
    • Sorensen, Poul. Department of Pathology and Laboratory Medicine, University of British Columbia, V6T 1Z4, Vancouver, BC, Canada
    • Gaide, Olivier. Department of Dermatology-Venereology, Geneva University Hospital, Michel-Servet 1, Geneva, Switzerland
    • Andera, Ladislav. Institute of Molecular Genetics, Czech Academy of Sciences, Prague, Czech Republic
    • Martinou, Jean-Claude. Department of Cell Biology, University of Geneva, Sciences III, 30 quai Ernest Ansermet, 1211, Geneva 4, Switzerland
    Document Type
    • Postprint
    OAI-PMH Identifier
    • oai:doc.rero.ch:317690
    Summary
    Recently, tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL/Apo2L) has been shown to be a potential candidate for cancer therapy. TRAIL induces apoptosis in various cancer cells but not in normal tissues. Here we show that HCT116 and SW480 cells with a deficient mitochondrial apoptotic pathway were resistant to TRAIL-induced apoptosis, whereas HCT116 and SW480 cells with a functional mitochondrial apoptotic pathway underwent apoptosis upon exposure to TRAIL. Surprisingly, TRAIL induced phenotypic changes in cells with a dysfunctional mitochondrial apoptotic pathway, including membrane blebbing and a transient loss of adhesion properties to the substratum. Accordingly, TRAIL stimulated the ability of these cells to migrate. This behavior was the consequence of a transient TRAIL-induced ROCK1 cleavage. In addition, we report that Bax-deficient HCT116 cells exposed to TRAIL for a prolonged period lost their sensitivity to TRAIL as a result of downregulation of TRAIL receptor expression, and became resistant to combination of TRAIL and other drugs such as MG-132 and bortezomib. These findings may have important consequences for TRAIL anti-cancer therapy