Wip1 promotes RUNX2-dependent apoptosis in p53-negative tumors and protects normal tissues during treatment with anticancer agents.
Proc Natl Acad Sci U S A
; 109(2): E68-75, 2012 Jan 10.
Article
en En
| MEDLINE
| ID: mdl-22065775
ABSTRACT
The inactivation of the p53 tumor suppressor pathway in many cancers often increases their resistance to anticancer therapy. Here we show that a previously proposed strategy directed to Wip1 inhibition could be ineffective in tumors lacking p53. On the contrary, Wip1 overexpression sensitized these tumors to chemotherapeutic agents. This effect was mediated through interaction between Wip1 and RUNX2 that resulted, in response to anticancer treatment, in RUNX2-dependent transcriptional induction of the proapoptotic Bax protein. The potentiating effects of Wip1 overexpression on chemotherapeutic agents were directed only to tumor cells lacking p53. The overexpression of Wip1 in normal tissues provided protection from cisplatin-induced apoptosis through decreased strength of upstream signaling to p53. Thus, Wip1 phosphatase promotes apoptosis in p53-negative tumors and protects normal tissues during treatment with anticancer agents.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Regulación Neoplásica de la Expresión Génica
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Proteína p53 Supresora de Tumor
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Fosfoproteínas Fosfatasas
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Subunidad alfa 1 del Factor de Unión al Sitio Principal
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Neoplasias
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Antineoplásicos
Límite:
Animals
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Female
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Humans
Idioma:
En
Año:
2012
Tipo del documento:
Article