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TGF-?/Smad signaling through DOCK4 facilitates lung adenocarcinoma metastasis.


ABSTRACT: The mechanisms by which TGF-? promotes lung adenocarcinoma (ADC) metastasis are largely unknown. Here, we report that in lung ADC cells, TGF-? potently induces expression of DOCK4, but not other DOCK family members, via the Smad pathway and that DOCK4 induction mediates TGF-?'s prometastatic effects by enhancing tumor cell extravasation. TGF-?-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-? and Rac1. Thus, our findings uncover the atypical Rac1 activator DOCK4 as a key component of the TGF-?/Smad pathway that promotes lung ADC cell extravasation and metastasis.

SUBMITTER: Yu JR 

PROVIDER: S-EPMC4318142 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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TGF-β/Smad signaling through DOCK4 facilitates lung adenocarcinoma metastasis.

Yu Jia-Ray JR   Tai Yilin Y   Jin Ying Y   Hammell Molly C MC   Wilkinson J Erby JE   Roe Jae-Seok JS   Vakoc Christopher R CR   Van Aelst Linda L  

Genes & development 20150201 3


The mechanisms by which TGF-β promotes lung adenocarcinoma (ADC) metastasis are largely unknown. Here, we report that in lung ADC cells, TGF-β potently induces expression of DOCK4, but not other DOCK family members, via the Smad pathway and that DOCK4 induction mediates TGF-β's prometastatic effects by enhancing tumor cell extravasation. TGF-β-induced DOCK4 stimulates lung ADC cell protrusion, motility, and invasion without affecting epithelial-to-mesenchymal transition. These processes, which a  ...[more]

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