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

Autor(es)

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

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: Free Radical Research; v. 52, n. 5, p. 592-604, 2018.
• Citações Web of Science: 5

Resumo

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)

• Processo FAPESP: 11/24112-7 - S-nitrosilação de Src quinase promovida por concentrações crescentes de óxido nítrico (NO): Implicações na morte por perda de adesão ao substrato (anoikis) induzida por NO
• Beneficiário: Paulo Eduardo da Costa
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 10/19013-7 - Participação da proteína tirosina quinase Src e do óxido nítrico nas vias de sinalização celular estimuladas por estrógeno em linhagens de tumores humanos de mama
• Beneficiário: Hugo Pequeno Monteiro
• Modalidade de apoio: Auxílio à Pesquisa - Regular