Regulation of focal adhesion turnover by ErbB signalling in invasive breast cancer cells.
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.
Xu
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Department of Medicine, Lady Davis Institute of the Sir Mortimer B. Davis Jewish General Hospital, Segal Comprehensive Cancer Center, McGill University, Montréal, Canada.
Benlimame
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N
Su
J
J
He
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Alaoui-Jamali
M A
MA
D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D022001:Focal Adhesions / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D009361:Neoplasm Invasiveness; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D051416:Focal Adhesion Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases