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Quantitative Measurement of Invadopodia-mediated Extracellular Matrix Proteolysis in Single and Multicellular Contexts
14:23

Quantitative Measurement of Invadopodia-mediated Extracellular Matrix Proteolysis in Single and Multicellular Contexts

Published on: August 27, 2012

19.1K

SNARE-dependent interaction of Src, EGFR and β1 integrin regulates invadopodia formation and tumor cell invasion

Karla C Williams1, Marc G Coppolino

  • 1Department of Molecular and Cellular Biology, University of Guelph, Guelph, ON N1G 2W1, Canada.

Journal of Cell Science
|February 6, 2014
PubMed

Insights

Tumor cell invasion relies on invadopodia formation, driven by Src, epidermal growth factor receptor (EGFR), and β1 integrin. SNARE proteins mediate trafficking of these molecules, crucial for cancer metastasis.

Area of Science:

  • Cell Biology
  • Cancer Research
  • Molecular Biology

Background:

  • Tumor metastasis requires an invasive phenotype, facilitated by invadopodia that degrade the extracellular matrix (ECM).
  • Invadosome formation depends on Src-mediated cytoskeletal rearrangements.

Purpose of the Study:

  • To investigate the association between Src, epidermal growth factor receptor (EGFR), and β1 integrin in invadopodia formation.
  • To elucidate the role of SNARE proteins (syntaxin13/STX12 and SNAP23) in mediating the trafficking of these components for tumor cell invasion.

Main Methods:

  • Investigated the association between Src, EGFR, and β1 integrin.
  • Examined the dependence of invadopodia formation and ECM degradation on syntaxin13 and SNAP23.
  • Assessed the impact of SNARE inhibition on the delivery of Src and EGFR to invadopodia.
  • Analyzed β1 integrin's role in regulating SNARE function and protein interactions.

Main Results:

  • Identified a Src-EGFR-β1 integrin association crucial for invadopodia formation.
  • Demonstrated that syntaxin13 and SNAP23 mediate the membrane traffic of Src and EGFR to invadopodia.
  • Showed that SNARE inhibition impairs Src/EGFR delivery and β1-integrin-dependent Src activation/EGFR phosphorylation.
  • Found that β1 integrin regulates SNARE-dependent trafficking, influencing Src and EGFR delivery for invasion.

Conclusions:

  • SNARE-dependent membrane trafficking is essential for delivering Src and EGFR to invadopodia formation sites.
  • β1 integrin plays a regulatory role in SNARE function, impacting tumor cell invasion.
  • Targeting this trafficking pathway could offer strategies to inhibit cancer metastasis.
Keywords:
EGFRIntegrinInvadopodiaSNARESrc

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