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PMID: 19190626 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Regulation of focal adhesion turnover by ErbB signalling in invasive breast cancer cells.

British journal of cancer ·Vol. 100 ·No. 4 ·2009-02-24 ·Pages 633-43

Xu Y, Benlimame N, Su J, He Q, Alaoui-Jamali MA

Abstract

A crucial early event by which cancer cells switch from localised to invasive phenotype is initiated by the acquisition of autonomous motile properties; a process driven by dynamic assembly and disassembly of multiple focal adhesion (FA) proteins, which mediate cell-matrix attachments, extracellular matrix degradation, and serve as traction sites for cell motility. We have reported previously that cancer cell invasion induced by overexpression of members of the ErbB tyrosine kinase receptors, including ErbB2, is dependent on FA signalling through FA kinase (FAK). Here, we show that ErbB2 receptor signalling regulates FA turnover, and cell migration and invasion through the Src-FAK pathway. Inhibition of the Src-FAK signalling in ErbB2-positive cells by Herceptin or RNA interference selectively regulates FA turnover, leading to enhanced number and size of peripherally localised adhesions and inhibition of cell invasion. Inhibition of ErbB2 signalling failed to regulate FA and cell migration and invasion in cells lacking FAK or Src but gains this activity after restoration of these proteins. Taken together, our results show a regulation of FA turnover by ErbB2 signalling.

MeSH Terms
Breast Neoplasms/genetics,metabolism,pathology Cell Line, Tumor Cell Movement Focal Adhesion Protein-Tyrosine Kinases/genetics,metabolism Focal Adhesions/genetics,metabolism Gene Expression Regulation Humans Neoplasm Invasiveness Receptor, ErbB-2/genetics,metabolism Signal Transduction
Chemicals
Receptor, ErbB-2 Focal Adhesion Protein-Tyrosine Kinases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Xu Y
Department of Medicine, Lady Davis Institute of the Sir Mortimer B. Davis Jewish General Hospital, Segal Comprehensive Cancer Center, McGill University, Montréal, Canada.
Benlimame N
Su J
He Q
Alaoui-Jamali M A
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Article Info
Journal
British journal of cancer
Abbr.
Br J Cancer
ISSN
1532-1827
DOI
10.1038/sj.bjc.6604901
Published
2009-02-24
Epub
2009-00-03
Pages
633-43
Language
English
Region
England
NLM ID
0370635
PMCID
PMC2653743
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.bjc.6604901 PMC Full Text View journal details
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