TGF-β/smad signaling through DOCK4 facilitates lung adenocarcinoma metastasis

Jia Ray Yu, Yilin Tai, Ying Jin, Molly C. Hammell, J. Erby Wilkinson, Jae Seok Roe, Christopher R. Vakoc, Linda Van Aelst

Research output: Contribution to journalArticle

38 Citations (Scopus)

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-b-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.

Original languageEnglish
Pages (from-to)250-261
Number of pages12
JournalGenes and Development
Volume29
Issue number3
DOIs
Publication statusPublished - 2015 Jan 1

All Science Journal Classification (ASJC) codes

  • Genetics
  • Developmental Biology

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    Yu, J. R., Tai, Y., Jin, Y., Hammell, M. C., Wilkinson, J. E., Roe, J. S., Vakoc, C. R., & Van Aelst, L. (2015). TGF-β/smad signaling through DOCK4 facilitates lung adenocarcinoma metastasis. Genes and Development, 29(3), 250-261. https://doi.org/10.1101/gad.248963.114