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Updated: May 31, 2026

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex
07:17

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex

Published on: August 2, 2021

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

Ernst J A Steller1, Laila Ritsma, Danielle A E Raats

  • 1Department of Surgery, University Medical Center Utrecht, The Netherlands.

EMBO Reports
|July 16, 2011
PubMed

Insights

This study reveals a novel CD95 signaling pathway crucial for colorectal cancer cell invasion. It involves tyrosine kinase activation, leading to actin remodeling and enhanced tumor cell motility.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • The death receptor CD95 (Fas/APO-1) is known to induce apoptosis via established signaling cascades.
  • In colorectal cancer, CD95 also promotes cell migration and invasion, but the underlying mechanisms remain poorly understood.

Purpose of the Study:

  • To elucidate the novel CD95-activated signaling pathway responsible for promoting colorectal cancer cell invasion.
  • To identify key molecular players involved in CD95-mediated tumor cell motility.

Main Methods:

  • Investigated CD95 signaling in colorectal cancer cells using molecular biology techniques.
  • Analyzed protein phosphorylation, receptor interactions, and downstream signaling events.
  • Examined the role of identified pathway components in cell invasion assays.

Main Results:

  • Identified a new CD95-activated tyrosine kinase pathway essential for tumor cell invasion.
  • Demonstrated that CD95 induces phosphorylation of phospholipase C-γ1 (PLCγ1) at Tyr 783 via platelet-derived growth factor receptor-β (PDGFR-β).
  • Showed that PLCγ1 activation leads to phosphatidylinositol (4,5)-bisphosphate (PIP(2)) hydrolysis, liberating cofilin and initiating actin remodeling for invasion.

Conclusions:

  • A novel CD95-activated tyrosine kinase pathway, involving PDGFR-β, PLCγ1, and cofilin, drives colorectal cancer cell invasion.
  • Targeting this pathway could offer new therapeutic strategies for inhibiting tumor metastasis.

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