TGF-beta/Smad signaling through DOCK4 facilitates lung adenocarcinoma metastasis

Yu, J. R., Tai, Y., Jin, Y., Hammell, M. C., Wilkinson, J. E., Roe, J. S., Vakoc, C. R., Van Aelst, L. (February 2015) TGF-beta/Smad signaling through DOCK4 facilitates lung adenocarcinoma metastasis. Genes Dev, 29 (3). pp. 250-61. ISSN 0890-9369

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URL: http://www.ncbi.nlm.nih.gov/pubmed/25644601

DOI: 10.1101/gad.248963.114

Abstract

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

Item Type:	Paper
Subjects:	bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > DOCK proteins diseases & disorders > cancer > cancer types > lung cancer diseases & disorders > cancer > metastasis bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > TGF-beta
CSHL Authors:	Hammell, Molly Jin, Ying Roe, Jae Seok Tai, Yilin Vakoc, Christopher R. Van Aelst, Linda Yu, Jia-Ray
Communities:	CSHL Cancer Center Program > Gene Regulation and Cell Proliferation CSHL Cancer Center Program > Signal Transduction CSHL Cancer Center Shared Resources > Animal Services CSHL Cancer Center Shared Resources > Animal Tissue and Imaging Service CSHL Cancer Center Shared Resources > Bioinformatics Service CSHL Cancer Center Shared Resources > Functional Genomics and Genetics Service CSHL Cancer Center Shared Resources > Microscopy Service CSHL labs > Hammell M. lab CSHL labs > Vakoc lab CSHL labs > Van Aelst lab CSHL Cancer Center Shared Resources > DNA Sequencing Service
Depositing User:	Matt Covey
Date:	1 February 2015
Date Deposited:	17 Feb 2015 19:50
Last Modified:	03 Nov 2017 19:57
PMCID:	PMC4318142
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/31221

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