SMARCE1 suppresses EGFR expression and controls responses to MET and ALK inhibitors in lung cancer.
Cell Res
; 25(4): 445-58, 2015 Apr.
Article
em En
| MEDLINE
| ID: mdl-25656847
ABSTRACT
Recurrent inactivating mutations in components of SWI/SNF chromatin-remodeling complexes have been identified across cancer types, supporting their roles as tumor suppressors in modulating oncogenic signaling pathways. We report here that SMARCE1 loss induces EGFR expression and confers resistance to MET and ALK inhibitors in non-small cell lung cancers (NSCLCs). We found that SMARCE1 binds to regulatory regions of the EGFR locus and suppresses EGFR transcription in part through regulating expression of Polycomb Repressive Complex component CBX2. Addition of the EGFR inhibitor gefitinib restores the sensitivity of SMARCE1-knockdown cells to MET and ALK inhibitors in NSCLCs. Our findings link SMARCE1 to EGFR oncogenic signaling and suggest targeted treatment options for SMARCE1-deficient tumors.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
1_ASSA2030
/
2_ODS3
Base de dados:
MEDLINE
Assunto principal:
Proteínas Cromossômicas não Histona
/
Carcinoma Pulmonar de Células não Pequenas
/
Proteínas de Ligação a DNA
/
Receptores ErbB
/
Neoplasias Pulmonares
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Cell Res
Ano de publicação:
2015
Tipo de documento:
Article