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

Elisabetta Iessi (1, 2) , Luciana Zischler (1, 3) , Aurélie Etringer (1, 2) , Marion Bergeret (1, 2) , Aymeric Morlé (1, 2) , Guillaume Jacquemin (1, 2) , Alexandre Morizot (1, 2) , Sarah Shirley (1, 2) , Najoua Lalaoui (1, 2) , Selene L. Elifio-Esposito (3) , Stefano Fais (4) , Carmen Garrido (1, 5, 2) , Eric Solary (6) , Olivier Micheau (1, 5, 2)

1 LNC - Lipides - Nutrition - Cancer (U866)
2 UFR des Sciences de Santé (Université de Bourgogne)
3 Pós-graduação em Ciências da Saúde [Paraná, Brazil]
4 Antitumor Drugs Section - Department of Therapeutic Research and Medicines Evaluation [Rome, Italy]
5 UNICANCER/CRLCC-CGFL - Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon]
6 Hématopoïèse normale et pathologique

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.

Domaines: Biochimie, Biologie Moléculaire

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, 2015, PLoS ONE, 10 (5), pp.e0126526. ⟨10.1371/journal.pone.0126526.s009⟩. ⟨inserm-01158055⟩