Journal
EMBO REPORTS
Volume 12, Issue 9, Pages 931-937Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/embor.2011.129
Keywords
CD95; colorectal; cancer; invasion; platelet-derived growth factor receptor; phospholipase
Categories
Funding
- Dutch Cancer Society [2009-4367, -4621, -4417, -4367, -4608]
- PON foundation
- Dutch Organization for Scientific Research [ZON-Mw VIDI 91710330, NWO 175.010.2007.00]
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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-gamma 1 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.
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