The study of anoikis - cell death promoted by loss of adhesion to a substrate - is of major importance to understand how metastatic tumor cells develop resistance to this particular type of cell death. For many years, our research group provided experimental evidence on the signaling properties of nitric oxide (NO) . The radical can signal through protein tyrosine kinases and integrins. The cytoplasmic protein tyrosine kinases Src and Focal adhesion kinase (FAK) are key elements in the connections between proliferative and adhesive signaling events. Both proteins constitute the major components of the focal adhesion complex. We and others recently demonstrated that low (physiological concentrations) of NO promote cell migration, proliferation, and cell survival. Such low concentrations were inhibitory of apoptosis in general and of anoikis in particular. On the other hand, high (non-physiological) concentrations of NO can promote cell detachment and consequently cell death. We recently provided experimental evidence to prove this point.Therefore, with this proposal we aimed to characterize in tumor cell lines exposed to increasing concentrations of NO donors, the role of s-nitrosylation of Src kinase promoted by such concentrations in the putative changes on the focal adhesion complex. The consequences of these changes and their relationship with the occurrence of anoikis will be investigated.
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