Epsin is required for Dishevelled stability and Wnt signalling activation in colon cancer development.
Nat Commun
; 6: 6380, 2015 Mar 16.
Article
en En
| MEDLINE
| ID: mdl-25871009
ABSTRACT
Uncontrolled canonical Wnt signalling supports colon epithelial tumour expansion and malignant transformation. Understanding the regulatory mechanisms involved is crucial for elucidating the pathogenesis of and will provide new therapeutic targets for colon cancer. Epsins are ubiquitin-binding adaptor proteins upregulated in several human cancers; however, the involvement of epsins in colon cancer is unknown. Here we show that loss of intestinal epithelial epsins protects against colon cancer by significantly reducing the stability of the crucial Wnt signalling effector, dishevelled (Dvl2), and impairing Wnt signalling. Consistently, epsins and Dvl2 are correspondingly upregulated in colon cancer. Mechanistically, epsin binds Dvl2 via its epsin N-terminal homology domain and ubiquitin-interacting motifs and prohibits Dvl2 polyubiquitination and degradation. Our findings reveal an unconventional role for epsins in stabilizing Dvl2 and potentiating Wnt signalling in colon cancer cells to ensure robust colon cancer progression. The pro-carcinogenic role of Epsins suggests that they are potential therapeutic targets to combat colon cancer.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Fosfoproteínas
/
Adenocarcinoma
/
Regulación Neoplásica de la Expresión Génica
/
Neoplasias del Colon
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Proteínas Adaptadoras del Transporte Vesicular
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Proteínas Adaptadoras Transductoras de Señales
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Vía de Señalización Wnt
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos