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

Genes & development (2015-02-04)
Jia-Ray Yu, Yilin Tai, Ying Jin, Molly C Hammell, J Erby Wilkinson, Jae-Seok Roe, Christopher R Vakoc, Linda Van Aelst
ABSTRACT

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 are fundamental to tumor cell extravasation, are driven by DOCK4-mediated Rac1 activation, unveiling a novel link between TGF-β and Rac1. Thus, our findings uncover the atypical Rac1 activator DOCK4 as a key component of the TGF-β/Smad pathway that promotes lung ADC cell extravasation and metastasis.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Trimesic acid, 95%
Sigma-Aldrich
Trimethylaluminum, 97%
Sigma-Aldrich
Trimethylaluminum solution, 2.0 M in toluene
Sigma-Aldrich
Trimethylaluminum solution, 2.0 M in hexanes
Sigma-Aldrich
Trimethylaluminum, packaged for use in deposition systems
Sigma-Aldrich
Trimethylaluminum solution, 2.0 M in heptane