1. ¹Department of Medicine, Lady Davis Institute of the Sir Mortimer B. Davis Jewish General Hospital, Segal Comprehensive Cancer Center, McGill University, Montréal, Canada
2. ²Department of Oncology, Lady Davis Institute of the Sir Mortimer B. Davis Jewish General Hospital, Segal Comprehensive Cancer Center, McGill University, Montréal, Canada

Correspondence: Professor MA Alaoui-Jamali, Lady Davis Institute for Medical Research and Segal Comprehensive Cancer Center, Room E534, 3755 Chemin de la Côte-Ste-Catherine, Montréal, Quebec, Canada H3T 1E2. E-mail: moulay.alaoui-jamali@mcgill.ca

³These authors contributed equally to this work.

⁴Current address: Department of Hepatobiliary Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510089, China

Revised 13 November 2008; Accepted 4 January 2009; Published online 3 February 2009.

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.