TGF-ß/Smad signaling through DOCK4 facilitates lung adenocarcinoma metastasis.
Genes Dev
; 29(3): 250-61, 2015 Feb 01.
Article
en En
| MEDLINE
| ID: mdl-25644601
ABSTRACT
The mechanisms by which TGF-ß promotes lung adenocarcinoma (ADC) metastasis are largely unknown. Here, we report that in lung ADC cells, TGF-ß potently induces expression of DOCK4, but not other DOCK family members, via the Smad pathway and that DOCK4 induction mediates TGF-ß's prometastatic effects by enhancing tumor cell extravasation. TGF-ß-induced DOCK4 stimulates lung ADC cell protrusion, motility, and invasion without affecting epithelial-to-mesenchymal transition. These processes, which are fundamental to tumor cell extravasation, are driven by DOCK4-mediated Rac1 activation, unveiling a novel link between TGF-ß and Rac1. Thus, our findings uncover the atypical Rac1 activator DOCK4 as a key component of the TGF-ß/Smad pathway that promotes lung ADC cell extravasation and metastasis.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Adenocarcinoma
/
Transducción de Señal
/
Factor de Crecimiento Transformador beta
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Proteínas Activadoras de GTPasa
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Proteínas Smad
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Neoplasias Pulmonares
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Genes Dev
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2015
Tipo del documento:
Article