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. 2004 Mar 1;378(Pt 2):559–567. doi: 10.1042/BJ20031392

Activated Src increases adhesion, survival and alpha2-integrin expression in human breast cancer cells.

Hee Boong Park 1, Vita Golubovskaya 1, Lihui Xu 1, Xihui Yang 1, Jin Woo Lee 1, Sean Scully 2nd 1, Rolf Joseph Craven 1, William G Cance 1
PMCID: PMC1223979  PMID: 14629195

Abstract

Focal adhesion kinase (FAK) is an intracellular kinase that localizes to focal adhesions. FAK is overexpressed in human tumours, and FAK regulates both cellular adhesion and anti-apoptotic survival signalling. Disruption of FAK function by overexpression of the FAK C-terminal domain [FAK-CD, analogous to the FRNK (FAK-related non-kinase) protein] leads to loss of adhesion and apoptosis in tumour cells. We have shown that overexpression of an activated form of the Src tyrosine kinase suppressed the loss of adhesion induced by dominant-negative; adenoviral FAK-CD and decreased the apoptotic response in BT474 and MCF-7 breast cancer cell lines. This adhesion-dependent apoptosis was increased by the Src-family kinase inhibitor PP2 [4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine]. We have also shown that expression of activated Src in breast cancer cells increased the expression of alpha2-integrin and that overexpression of alpha2-integrin suppressed FAK-CD-mediated loss of adhesion. Our results suggest a model in which Src regulates adhesion and survival through enhanced expression of the alpha2-integrin. This provides a mechanism through which Src promotes cellular adhesion and alters the adhesive function of FAK.

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Selected References

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