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The death receptor CD95 activates the cofilin pathway to stimulate tumour cell invasion
Author(s) -
Steller Ernst J A,
Ritsma Laila,
Raats Danielle A E,
Hoogwater Frederik J H,
Emmink Benjamin L,
Govaert Klaas M,
Laoukili Jamila,
Borel Rinkes Inne H M,
van Rheenen Jacco,
Kranenburg Onno
Publication year - 2011
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2011.129
Subject(s) - cofilin , fas receptor , microbiology and biotechnology , signal transduction , tyrosine phosphorylation , receptor tyrosine kinase , biology , actin remodeling , phosphatidylinositol , actin , apoptosis , programmed cell death , chemistry , actin cytoskeleton , cell , cytoskeleton , biochemistry
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.