title: The death receptor CD95 activates the cofilin pathway to stimulate tumour cell invasion.
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-γ1 through the platelet-derived growth factor receptor-β, 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.
authors.affiliation: Department of Surgery, University Medical Center Utrecht, The Netherlands.
authors.forename: Ernst J A
authors.initials: EJ
authors.lastname: Steller
authors.forename: Laila
authors.initials: L
authors.lastname: Ritsma
authors.forename: Danielle A E
authors.initials: DA
authors.lastname: Raats
authors.forename: Frederik J H
authors.initials: FJ
authors.lastname: Hoogwater
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Emmink
authors.forename: Klaas M
authors.initials: KM
authors.lastname: Govaert
authors.forename: Jamila
authors.initials: J
authors.lastname: Laoukili
authors.forename: Inne H M Borel
authors.initials: IH
authors.lastname: Rinkes
authors.forename: Jacco
authors.initials: J
authors.lastname: van Rheenen
authors.forename: Onno
authors.initials: O
authors.lastname: Kranenburg
mesh_terms: D051339:Actin Depolymerizing Factors / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D022081:Cell Surface Extensions; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009361:Neoplasm Invasiveness; D010716:Phosphatidylinositols / Q000378:metabolism*; D051966:Phospholipase C gamma / Q000378:metabolism; D010766:Phosphorylation; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D053218:Receptors, Death Domain / Q000378:metabolism; D015398:Signal Transduction; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D010716:Phosphatidylinositols; D053218:Receptors, Death Domain; D019014:fas Receptor; D020797:Receptor, Platelet-Derived Growth Factor beta; D051966:Phospholipase C gamma