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. 2003 Jul 1;373(Pt 1):201–210. doi: 10.1042/BJ20021846

Focal adhesion kinase N-terminus in breast carcinoma cells induces rounding, detachment and apoptosis.

Lucia Beviglia 1, Vita Golubovskaya 1, LiHui Xu 1, XiHui Yang 1, Rolf J Craven 1, William G Cance 1
PMCID: PMC1223465  PMID: 12659633

Abstract

Focal adhesion kinase (FAK) has a central role in adhesion-mediated cell signalling. The N-terminus of FAK is thought to function as a docking site for a number of proteins, including the Src-family tyrosine kinases. In the present study, we disrupted FAK signalling by expressing the N-terminal domain of FAK (FAK-NT) in human breast carcinoma cells, BT474 and MCF-7 lines, and non-malignant epithelial cells, MCF-10A line. Expression of FAK-NT led to rounding, detachment and apoptosis in human breast cancer cells. Apoptosis was accompanied by dephosphorylation of FAK Tyr(397), degradation of the endogenous FAK protein and activation of caspase-3. Over-expression of FAK rescued FAK-NT-mediated cellular rounding. Expression of FAK-NT in non-malignant breast epithelial cells did not lead to rounding, loss of FAK phosphorylation or apoptosis. Thus FAK-NT contributes to cellular adhesion and survival pathways in breast cancer cells which are not required for survival in non-malignant breast epithelial cells.

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Selected References

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