Focal Adhesion Kinase N-terminus in Breast Carcinoma Cells Induces Rounding, Detachment and Apoptosis

Overview

Journal Biochem J

Specialty Biochemistry

Date 2003 Mar 28

PMID 12659633

Citations 23

Authors

Lucia Beviglia

Vita Golubovskaya

Lihui Xu

Xihui Yang

Rolf J Craven

William G Cance

Affiliations

Soon will be listed here.

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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