EGF-induced nuclear localization of SHCBP1 activates ß-catenin signaling and promotes cancer progression.
Oncogene
; 38(5): 747-764, 2019 01.
Article
en En
| MEDLINE
| ID: mdl-30177836
ABSTRACT
Aberrant activation of EGFR represents a common event in non-small cell lung carcinoma (NSCLC) and activates various downstream signaling pathways. While EGFR activation of ß-catenin signaling was previously reported, the mediating mechanism remains unclear. Our current study found that EGFR activation in NSCLC cells releases SHC-binging protein 1 (SHCBP1) from SHC adaptor protein 1 (SHC1), which subsequently translocates into the nucleus and directly promotes the transactivating activity of ß-catenin, consequently resulting in development of NSCLC cell stemness and malignant progression. Furthermore, SHCBP1 promotes ß-catenin activity through enhancing the CBP/ß-catenin interaction, and most interestingly, a candidate drug that blocks the CBP/ß-catenin binding effectively abrogates the aforementioned biological effects of SHCBP1. Clinically, SHCBP1 level in NSCLC tumors was found to inversely correlate with patient survival. Together, our study establishes a novel convergence between EGFR and ß-catenin pathways and highlights a potential significance of SHCBP1 as a prognostic biomarker and a therapeutic target.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Núcleo Celular
/
Carcinoma de Pulmón de Células no Pequeñas
/
Factor de Crecimiento Epidérmico
/
Beta Catenina
/
Proteínas Adaptadoras de la Señalización Shc
/
Neoplasias Pulmonares
/
Proteínas de Neoplasias
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Oncogene
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2019
Tipo del documento:
Article
País de afiliación:
China