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Gynecol Oncol. 2002 May;85(2):339-50.

Caspase 3-mediated focal adhesion kinase processing in human ovarian cancer cells: possible regulation by X-linked inhibitor of apoptosis protein.

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Reproductive Biology Unit, Department of Obstetrics and Gynecology, University of Ottawa, Ottawa, Ontario, Canada K1Y 4E9.



Cell adhesion is an important cell survival determinant and disruption of integrin-mediated signal transduction may be involved in anchorage-dependent cell death. We have examined the processing of focal adhesion kinase (FAK), a component of integrin-mediated signal transduction, in a cisplatin-sensitive human ovarian epithelial cancer cell line (OV2008), to test the possible role of FAK degradation in the control of apoptosis via regulation of cell attachment.


FAK processing after cisplatin treatment in the absence or presence of various caspase-inhibiting substances was analyzed by Western blot. Caspase-inhibiting activities were introduced using cell-permeable peptides or adenoviral vector.


Cisplatin-induced caspase 3 and FAK cleavage, cell detachment from the growth surface, and apoptosis in a temporally related and concentration-dependent manner. FAK fragments were detected exclusively in cells detached from the culture surface. Addition of active caspase 3 to the whole cell lysate elicited a similar pattern of FAK cleavage. Pretreatment of whole cell lysates and cells with tetrapeptide inhibitors of caspases significantly decreased FAK cleavage induced by exogenous active caspase 3 and cisplatin, respectively. Overexpression of X-linked inhibitor of apoptosis protein (Xiap), an endogenous caspase inhibitor, attenuated the cisplatin-induced FAK processing, morphologic changes, and apoptosis. The inhibitory action of Xiap was abolished with the deletion of a functional motif required for caspase inhibition.


These findings are consistent with our hypothesis that FAK processing is in part mediated by caspase 3, the activation of which is modulated by Xiap.

[Indexed for MEDLINE]

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