RASSF6-mediated inhibition of Mcl-1 through JNK activation improves the anti-tumor effects of sorafenib in renal cell carcinoma.
Cancer Lett
; 432: 75-83, 2018 09 28.
Article
em En
| MEDLINE
| ID: mdl-29864454
ABSTRACT
Ras association domain family member 6 (RASSF6) has been shown to act as a tumor suppressor and predictor of poor prognosis in renal cell carcinoma (RCC). However, little is known about the effects of RASSF6 on sorafenib resistance or the underlying mechanism. Here, we show that RASSF6 expression positively correlates with sorafenib sensitivity in RCC cells and human samples. Stable ectopic overexpression of RASSF6 in RCC cell lines reduces resistance to sorafenib in vitro and in vivo. At a molecular level, RASSF6 activates the JNK signaling pathway, which further contributes to Mcl-1 inhibition. Suppression of the JNK pathway can partially restore Mcl-1 expression and sorafenib resistance. Together, these findings suggest that RASSF6 inhibits sorafenib resistance by repressing Mcl-1 through the JNK-dependent pathway. RASSF6 may serve as a novel regulator for sorafenib therapy in RCC.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Carcinoma de Células Renais
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Regulação Neoplásica da Expressão Gênica
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Resistencia a Medicamentos Antineoplásicos
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Proteínas Monoméricas de Ligação ao GTP
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MAP Quinase Quinase 4
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Proteína de Sequência 1 de Leucemia de Células Mieloides
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Sorafenibe
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article