SnoN/SkiL expression is modulated via arsenic trioxide-induced activation of the PI3K/AKT pathway in ovarian cancer cells.
FEBS Lett
; 587(1): 5-16, 2013 Jan 04.
Article
em En
| MEDLINE
| ID: mdl-23178716
ABSTRACT
SnoN/SkiL (TGFß regulator) is dysregulated in ovarian cancer, a disease associated with acquired drug-resistance. Arsenic trioxide (As2O3, used in treating APL) induces SnoN to oppose the apoptotic response in ovarian cancer cells. We now report that As2O3 increases phosphorylation of EGFR/p66ShcA and EGFR degradation. As2O3 activates Src(Y416) whose activity (inhibited by PP2) modulates EGFR activation, its interaction with Shc/Grb2, and p-AKT. Inhibition of PI3K reduces SnoN and cell survival. Although EGFR or MAPK1 siRNA did not alter SnoN expression, As2O3-induced cleaved PARP was reduced together with increased XIAP. Collectively, As2O3 mediates an initial rise in pY-Src(416) to regulate the PI3K/AKT pathway which increases SnoN and cell survival; these early events may counter the cell death response associated with increased pY-EGFR/MAPK activation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ovarianas
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Óxidos
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Arsenicais
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Transdução de Sinais
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Regulação Neoplásica da Expressão Gênica
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Proteínas Proto-Oncogênicas
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Fosfatidilinositol 3-Quinases
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Peptídeos e Proteínas de Sinalização Intracelular
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Antineoplásicos
Idioma:
En
Revista:
FEBS Lett
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos