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

• Published in: Biochemical journal 2003-07, Vol.373 (Pt 1), p.201-210
• Main Authors: Beviglia, Lucia, Golubovskaya, Vita, Xu, LiHui, Yang, XiHui, Craven, Rolf J, Cance, William G
• Format: Article
• Language: English
• Subjects: Apoptosis - physiology; Base Sequence; Breast Neoplasms - enzymology; Breast Neoplasms - pathology; Caspase 3; Caspases - metabolism; Cell Size; DNA Primers; DNA, Complementary; Enzyme Activation; Female; Focal Adhesion Kinase 1; Focal Adhesion Protein-Tyrosine Kinases; Humans; Peptide Fragments - metabolism; Polymerase Chain Reaction; Protein-Tyrosine Kinases - chemistry; Protein-Tyrosine Kinases - genetics; Protein-Tyrosine Kinases - metabolism; Recombinant Fusion Proteins - metabolism; Transfection; Tumor Cells, Cultured
• ISSN: 0264-6021; 1470-8728
• DOI: 10.1042/bj20021846

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.