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Cited by 66TGF-β signaling in diseasesMechanisms of cancer metastasisProtein Kinase Regulation and GTPase Signaling

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

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Yu, Jia-Ray, Tai, Yilin, Jin, Ying, Hammell, Molly C., Wilkinson, J. Erby, Roe, Jae-Seok, Vakoc, Christopher R., Van Aelst, Linda·2015·Genes & Development
DOI 10.1101/gad.248963.114PMC PMC4318142
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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.

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  • Upregulation of DOCK4 was found associated with metastases of breast and lung cancer.

    “Upregulation of DOCK4 was found associated with metastases of breast and lung cancer (39, 40).”

    From miR-33b-3p Acts as a Tumor Suppressor by Targeting DOCK4 in Prostate Cancer (2021) · cites this paper as [39]

    The Results and Discussion support the lung-cancer portion: DOCK4 is upregulated by TGF-β in lung adenocarcinoma cells, and the paper reports a role for DOCK4 in lung adenocarcinoma metastasis. They do not support the breast-cancer portion; the paper reports no TGF-β-induced DOCK4 expression in breast cancer cells and no correlation between DOCK4 expression and breast-cancer relapse. No page numbers are available in our copy. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Yu, J.-R., Tai, Y., Jin, Y., Hammell, M. C., Wilkinson, J. E., Roe, J.-S., Vakoc, C. R., & Van Aelst, L.
Affiliations
  • Cold Spring Harbor Laboratory (US)
  • University of Michigan (US)
ORCID
Venue
Genes & Development
Publisher
Cold Spring Harbor Laboratory
Published
2015-02-01
Volume
29
Issue
3
Pages
250-261
ISSN
  • 0890-9369 (ISSN-L)
  • 1549-5477
DOI
10.1101/gad.248963.114
PMC
PMC4318142
OpenAlex
W1967801503
Cited by
66
References
1
Citations by year
2026: 1 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 5 · 2021: 11 · 2020: 9 · 2019: 12 · 2018: 5 · 2017: 9 · 2016: 6 · 2015: 1
Type
posted content
Language
en
Open access
Licence
cc-by-nc
Locations
  • Genes & Development (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
  • Academic Commons (Stony Brook University) (submittedVersion)
Funders
  • National Institutes of Health (CA135053)
  • New York STARR Foundation (14-A415/STARR)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
TGF-β/Smad signaling, DOCK4, lung adenocarcinoma, metastasis, tumor cell extravasation, Rac1 activation, cell motility, cell invasion, cell protrusions, epithelial-mesenchymal transition
MeSH terms
Adenocarcinoma of Lung, Adenocarcinoma, Animals, Humans, Lung Neoplasms, Neoplasm Metastasis, Signal Transduction, Gene Expression Regulation, Neoplastic, Transforming Growth Factor beta, GTPase-Activating Proteins, Cell Line, Tumor, Mice, Smad Proteins

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