Attenuation of the expression of the focal adhesion kinase induces apoptosis in tumor cells

The focal adhesion kinase (FAK) is a nonreceptor protein tyrosine kinase implicated in integrin-mediated signal transduction pathways, oncogenic transformation by v-src, and the invasion of human tumors, The overexpression of p125(FAK) in a variety of human tumors and tumor cell lines in comparison to their nontransformed counterparts suggested that attenuation of p125(FAK) expression might have an effect on tumor cell proliferation, In this study, we have treated tumor cell lines that expressed high levels of p125(FAK) With different antisense oligonucleotides to FAK, and have specifically attenuated p125(FAK) expression, The cells treated with antisense oligonucleotides not only lost their attachment, but also underwent apoptosis, Extensive control oligonucleotide experiments suggested that this attenuation was highly FAK specific, Furthermore, normal human fibroblasts, which did not express high levels of p125(FAK), did not lose their attachment or become apoptotic with FAK antisense treatment, These results suggested that FAK is involved in adhesion-mediated growth in tumor cells and that FAK may be a rational gene-directed target for disrupting tumor cell growth.