The death receptor CD95 activates the cofilin pathway to stimulate tumour cell invasion

E.J. Steller, L. Ritsma, D.A. Raats, F.J. Hoogwater, B.L. Emmink, K.M. Govaert, J. Laoukili, I.H. Rinkes, J. van Rheenen, O. Kranenburg

Research output: Contribution to journal/periodicalArticleScientificpeer-review

Abstract

The death receptor CD95 promotes apoptosis through well-defined signalling pathways. In colorectal cancer cells, CD95 primarily stimulates migration and invasion through pathways that are incompletely understood. Here, we identify a new CD95-activated tyrosine kinase pathway that is essential for CD95-stimulated tumour cell invasion. We show that CD95 promotes Tyr 783 phosphorylation of phospholipase C-gamma1 through the platelet-derived growth factor receptor-beta, resulting in ligand-stimulated phosphatidylinositol (4,5)-bisphosphate (PIP(2)) hydrolysis. PIP(2) hydrolysis liberates the actin-severing protein cofilin from the plasma membrane to initiate cortical actin remodelling. Cofilin activation is required for CD95-stimulated formation of membrane protrusions and increased tumour cell invasion.
Original languageEnglish
Pages (from-to)931-937
JournalEMBO Reports
Volume12
Issue number9
DOIs
Publication statusPublished - 2011

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