Skip to Main content Skip to Navigation
Journal articles

Death Receptor-Induced Apoptosis Signalling Regulation by Ezrin Is Cell Type Dependent and Occurs in a DISC-Independent Manner in Colon Cancer Cells

Abstract : Ezrin belongs to the ERM (ezrin-radixin-moesin) protein family and has been demonstrated to regulate early steps of Fas receptor signalling in lymphoid cells, but its contribution to TRAIL-induced cell death regulation in adherent cancer cells remains unknown. In this study we report that regulation of FasL and TRAIL-induced cell death by ezrin is cell type depen-dant. Ezrin is a positive regulator of apoptosis in T-lymphoma cell line Jurkat, but a negative regulator in colon cancer cells. Using ezrin phosphorylation or actin-binding mutants, we provide evidence that negative regulation of death receptor-induced apoptosis by ezrin occurs in a cytoskeleton-and DISC-independent manner, in colon cancer cells. Remarkably, inhibition of apoptosis induced by these ligands was found to be tightly associated with regulation of ezrin phosphorylation on serine 66, the tumor suppressor gene WWOX and activation of PKA. Deficiency in WWOX expression in the liver cancer SK-HEP1 or the pancreatic Mia PaCa-2 cell lines as well as WWOX silencing or modulation of PKA activation by pharmacological regulators, in the colon cancer cell line SW480, abrogated regulation of TRAIL signalling by ezrin. Altogether our results show that death receptor pro-apoptotic signalling regulation by ezrin can occur downstream of the DISC in colon cancer cells.
Document type :
Journal articles
Complete list of metadatas

https://www.hal.inserm.fr/inserm-01158055
Contributor : Olivier Micheau <>
Submitted on : Tuesday, January 3, 2017 - 4:41:23 PM
Last modification on : Wednesday, September 16, 2020 - 5:11:59 PM
Long-term archiving on: : Tuesday, April 4, 2017 - 12:04:41 PM

Files

art 68 Plos One 2015 Ezrin Ies...
Publisher files allowed on an open archive

Licence


Public Domain

Identifiers

Citation

Elisabetta Iessi, Luciana Zischler, Aurélie Etringer, Marion Bergeret, Aymeric Morlé, et al.. Death Receptor-Induced Apoptosis Signalling Regulation by Ezrin Is Cell Type Dependent and Occurs in a DISC-Independent Manner in Colon Cancer Cells. PLoS ONE, Public Library of Science, 2015, PLoS ONE, 10 (5), pp.e0126526. ⟨10.1371/journal.pone.0126526.s009⟩. ⟨inserm-01158055⟩

Share

Metrics

Record views

293

Files downloads

348