TGF-ß/Smad signaling through DOCK4 facilitates lung adenocarcinoma metastasis.
Genes Dev
; 29(3): 250-61, 2015 Feb 01.
Article
em 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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Adenocarcinoma
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Transdução de Sinais
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Fator de Crescimento Transformador beta
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Proteínas Ativadoras de GTPase
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Proteínas Smad
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Neoplasias Pulmonares
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article