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S-nitrosylation of Src kinase induced by increasing concentrations of nitric oxide (NO): Implications in cell death by loss of adhesion to the substrate (anoikis) induced by NO

Grant number: 11/24112-7
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): April 01, 2012
Effective date (End): March 31, 2016
Field of knowledge:Biological Sciences - Biochemistry - Metabolism and Bioenergetics
Principal Investigator:Hugo Pequeno Monteiro
Grantee:Paulo Eduardo da Costa
Host Institution: Centro de Terapia Celular e Molecular. Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil


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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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DA COSTA, PAULO E.; BATISTA, WAGNER L.; MORAES, MIRIAM S.; STERN, ARNOLD; MONTEIRO, HUGO P.. Src kinase activation by nitric oxide promotes resistance to anoikis in tumour cell lines. Free Radical Research, v. 52, n. 5, p. 592-604, . (11/24112-7, 10/19013-7)

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