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

28 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

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Neoplasm Metastasis
Epithelial-Mesenchymal Transition
Cell Movement
Neoplasms
Adenocarcinoma of lung

All Science Journal Classification (ASJC) codes

  • Genetics
  • Developmental Biology

Cite this

Yu, J. R., Tai, Y., Jin, Y., Hammell, M. C., Wilkinson, J. E., Roe, J-S., ... 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
Yu, Jia Ray ; Tai, Yilin ; Jin, Ying ; Hammell, Molly C. ; Wilkinson, J. Erby ; Roe, Jae-Seok ; Vakoc, Christopher R. ; Van Aelst, Linda. / TGF-β/smad signaling through DOCK4 facilitates lung adenocarcinoma metastasis. In: Genes and Development. 2015 ; Vol. 29, No. 3. pp. 250-261.
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Yu, JR, Tai, Y, Jin, Y, Hammell, MC, Wilkinson, JE, Roe, J-S, Vakoc, CR & Van Aelst, L 2015, 'TGF-β/smad signaling through DOCK4 facilitates lung adenocarcinoma metastasis', Genes and Development, vol. 29, no. 3, pp. 250-261. https://doi.org/10.1101/gad.248963.114

TGF-β/smad signaling through DOCK4 facilitates lung adenocarcinoma metastasis. / Yu, Jia Ray; Tai, Yilin; Jin, Ying; Hammell, Molly C.; Wilkinson, J. Erby; Roe, Jae-Seok; Vakoc, Christopher R.; Van Aelst, Linda.

In: Genes and Development, Vol. 29, No. 3, 01.01.2015, p. 250-261.

Research output: Contribution to journalArticle

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