Regulation of focal adhesion turnover by ErbB signalling in invasive breast cancer cells
Open Access
- 3 February 2009
- journal article
- Published by Springer Nature in British Journal of Cancer
- Vol. 100 (4), 633-643
- https://doi.org/10.1038/sj.bjc.6604901
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.Keywords
This publication has 46 references indexed in Scilit:
- Focal Adhesion Kinase-Related Proline-Rich Tyrosine Kinase 2 and Focal Adhesion Kinase Are Co-Overexpressed in Early-Stage and Invasive ErbB-2-Positive Breast Cancer and Cooperate for Breast Cancer Cell Tumorigenesis and InvasivenessThe American Journal of Pathology, 2008
- Antitumor Activity and Pharmacology of a Selective Focal Adhesion Kinase Inhibitor, PF-562,271Cancer Research, 2008
- Src SH2 Arginine 175 Is Required for Cell Motility: Specific Focal Adhesion Kinase Targeting and Focal Adhesion Assembly FunctionMolecular and Cellular Biology, 2006
- Akt Blocks Breast Cancer Cell Motility and Invasion through the Transcription Factor NFATMolecular Cell, 2005
- PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patientsCancer Cell, 2004
- FAK–Src signalling through paxillin, ERK and MLCK regulates adhesion disassemblyNature Cell Biology, 2004
- Combined trastuzumab and paclitaxel treatment better inhibits ErbB‐2‐mediated angiogenesis in breast carcinoma through a more effective inhibition of Akt than either treatment aloneCancer, 2003
- Structure of the extracellular region of HER2 alone and in complex with the Herceptin FabNature, 2003
- Src Catalytic but Not Scaffolding Function Is Needed for Integrin-Regulated Tyrosine Phosphorylation, Cell Migration, and Cell SpreadingMolecular and Cellular Biology, 2002
- Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient miceNature, 1995