Src kinase activation by nitric oxide promotes resistance to anoikis in tumour cell lines

Author(s)

da Costa, Paulo E. ^[1] ; Batista, Wagner L. ^[2] ; Moraes, Miriam S. ^[3] ; Stern, Arnold ^[4] ; Monteiro, Hugo P. ^[1]

Affiliation

^[1] Univ Fed Sao Paulo, Escola Paulista Med, Dept Biochem, Ctr Cellular & Mol Therapy CTCMol, Campus Sao Paulo, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Dept Pharmaceut Sci, Campus Diadema, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Inst Biosci, Sao Paulo - Brazil

^[4] NYU, Sch Med, New York, NY - USA

• Document type: Journal article
• Source: Free Radical Research; v. 52, n. 5, p. 592-604, 2018.
• Web of Science Citations: 5

Abstract

Tumour progression involves the establishment of tumour metastases at distant sites. Resistance to anoikis, a form of cell death that occurs when cells lose contact with the extracellular matrix and with neighbouring cells, is essential for metastases. NO has been associated with anoikis. NO treated HeLa cells and murine melanoma cells in suspension triggered a nitric oxide (NO)-Src kinase signalling circuitry that enabled resistance to anoikis. Two NO donors, sodium nitroprusside (SNP) (500 mu m) and DETANO (125 mu M), protected against cell death derived from detachment of a growth permissive surface (experimental anoikis). Under conditions of NO-mediated Src activation the following were observed: (a) down-regulation of the pro-apoptotic proteins Bim and cleaved caspase-3 and the cell surface protein, E-cadherin, (b) up-regulation of caveolin-1, and (c) the dissociation of cell aggregates formed when cells are detached from a growth permissive surface. Efficiency of reattachment of tumour cells in suspension and treated with different concentrations of an NO donor, was dependent on the NO concentration. These findings indicate that NO-activated Src kinase triggers a signalling circuitry that provides resistance to anoikis, and allows for metastases. (AU)

• FAPESP's process: 11/24112-7 - 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
• Grantee: Paulo Eduardo da Costa
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 10/19013-7 - Participation of nitric oxide and Src kinase in the estrogen-stimulated cell signaling pathway in human mammary tumor cells
• Grantee: Hugo Pequeno Monteiro
• Support type: Regular Research Grants