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

被引:33
作者
Xu, Y. [1 ,2 ]
Benlimame, N. [1 ,2 ]
Su, J. [1 ,2 ]
He, Q. [1 ,2 ]
Alaoui-Jamali, M. A. [1 ,2 ]
机构
[1] McGill Univ, Dept Med, Sir Mortimer B Davis Jewish Hosp, Lady Davis Inst,Segal Comprehens Canc Ctr, Montreal, PQ, Canada
[2] McGill Univ, Dept Oncol, Sir Mortimer B Davis Jewish Hosp, Lady Davis Inst,Segal Comprehens Canc Ctr, Montreal, PQ, Canada
关键词
breast cancer; ErbB2/Her-2; focal adhesion; cell invasion; metastases; PAXILLIN TYROSINE PHOSPHORYLATION; SRC FAMILY KINASES; MONOCLONAL-ANTIBODY; ANTITUMOR-ACTIVITY; MATRIX ADHESIONS; GROWTH-FACTOR; HERCEPTIN; MOTILITY; FAK; INHIBITION;
D O I
10.1038/sj.bjc.6604901
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:633 / 643
页数:11
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