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Updated: Aug 30, 2026

Analysis of Cell Migration within a Three-dimensional Collagen Matrix
08:02

Analysis of Cell Migration within a Three-dimensional Collagen Matrix

Published on: October 5, 2014

Multiple G-protein-coupled receptor signals converge on the epidermal growth factor receptor to promote migration and

Beatrix Schäfer1, Andreas Gschwind, Axel Ullrich

  • 1Department of Molecular Biology, Max-Planck Institute of Biochemistry, Martinsried D-82152, Germany.

Oncogene
|December 3, 2003
PubMed

Insights

G-protein-coupled receptor (GPCR) signaling activates epidermal growth factor receptor (EGFR) transactivation, promoting cancer cell migration and invasion. This metalloproteinase-dependent pathway offers a novel target for cancer intervention strategies.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signalling

Background:

  • G-protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs) regulate cellular processes; their deregulation is linked to tumorigenesis.
  • Understanding GPCR pathway regulation in kidney and bladder cancers is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate pathophysiological processes regulated by GPCR pathways in human kidney and bladder cancer cell lines.
  • To elucidate the role of EGFR transactivation in GPCR-mediated signaling and cancer cell behavior.

Main Methods:

  • Analysis of GPCR ligand-induced signaling in cancer cell lines.
  • Assessment of epidermal growth factor receptor (EGFR) phosphorylation and downstream mitogen-activated protein kinase (MAPK) activation.
  • Identification of EGFR ligands and metalloproteinases involved in transactivation.

Main Results:

  • GPCR ligands induced EGFR tyrosine phosphorylation and downstream signaling, including Shc recruitment and MAPK activation (ERK1/2, JNK, p38).
  • EGFR transactivation involved specific EGFR ligands (amphiregulin, HB-EGF, TGFα) and metalloproteinases (ADAM 10, 15, 17).
  • EGFR transactivation modulated the migratory and invasive behavior of kidney and bladder cancer cells.

Conclusions:

  • Metalloproteinase-mediated EGFR transactivation is a key mechanism in GPCR signaling networks.
  • This pathway promotes MAPK activation and enhances tumor cell migration and invasion.
  • EGFR transactivation represents a novel therapeutic target for cancer intervention.

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