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

doi:10.1038/embor.2011.129

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

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

43 Citations (Scopus)

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 language	English
Pages (from-to)	931-937
Journal	EMBO Reports
Volume	12
Issue number	9
DOIs	https://doi.org/10.1038/embor.2011.129
Publication status	Published - 2011

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10.1038/embor.2011.129

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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-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.",

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

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T1 - The death receptor CD95 activates the cofilin pathway to stimulate tumour cell invasion

AU - Steller, E.J.

AU - Ritsma, L.

AU - Raats, D.A.

AU - Hoogwater, F.J.

AU - Emmink, B.L.

AU - Govaert, K.M.

AU - Laoukili, J.

AU - Rinkes, I.H.

AU - van Rheenen, J.

AU - Kranenburg, O.

N1 - Reporting year: 2011 Metis note: 3166455;

PY - 2011

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AB - 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.

U2 - 10.1038/embor.2011.129

DO - 10.1038/embor.2011.129

M3 - Article

SN - 1469-221X

VL - 12

SP - 931

EP - 937

JO - EMBO Reports

JF - EMBO Reports

IS - 9

ER -

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

Abstract

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