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Cited by 262TGF-β signaling in diseasesCancer Cells and MetastasisKruppel-like factors research

Dual roles of myocardin-related transcription factors in epithelial–mesenchymal transition via slug induction and actin remodeling

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Morita, Tsuyoshi, Mayanagi, Taira, Sobue, Kenji·2007·The Journal of Cell Biology
DOI 10.1083/jcb.200708174PMC PMC2099179
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Abstract

Epithelial–mesenchymal transition (EMT) is a critical process occurring during embryonic development and in fibrosis and tumor progression. Dissociation of cell–cell contacts and remodeling of the actin cytoskeleton are major events of the EMT. Here, we show that myocardin-related transcription factors (MRTFs; also known as MAL and MKL) are critical mediators of transforming growth factor β (TGF-β) 1–induced EMT. In all epithelial cell lines examined here, TGF-β1 triggers the nuclear translocation of MRTFs. Ectopic expression of constitutive-active MRTF-A induces EMT, whereas dominant-negative MRTF-A or knockdown of MRTF-A and -B prevents the TGF-β1–induced EMT. MRTFs form complexes with Smad3. Via Smad3, the MRTF–Smad3 complexes bind to a newly identified cis-element GCCG-like motif in the promoter region of Canis familiaris and the human slug gene, which activates slug transcription and thereby dissociation of cell–cell contacts. MRTFs also increase the expression levels of actin cytoskeletal proteins via serum response factor, thereby triggering reorganization of the actin cytoskeleton. Thus, MRTFs are important mediators of TGF-β1–induced EMT.

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  • MRTFB protein is essential for EMT because it is the principal activator of SNAI1 and it cooperates with MRTFA protein to regulate SNAI2.

    “MRTFB protein is essential for EMT because it is the principal activator of SNAI1 and it cooperates with MRTFA protein to regulate SNAI2 [37, 65].”

    From Mechanical stiffness orchestrates distinct regulation of <scp>MRTFs</scp> and <scp>YAP</scp> / <scp>TAZ</scp> transcriptional cofactors in hepatocytes (2026) · cites this paper as [65]

    The Results sections on TGF-β1-induced EMT and slug promoter activity report that MRTF-A/B depletion suppresses EMT and reduces slug (SNAI2) promoter activation. They do not establish that MRTF-B cooperates specifically with MRTF-A. The Discussion says snail (SNAI1) regulation varies by cell type and that its transient induction in HK-2 cells was MRTF independent, rather than identifying MRTF-B as its principal activator. Page numbers are unavailable in our copy. (LLM, conf=0.87)

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Authors
Morita, T., Mayanagi, T., & Sobue, K.
Affiliations
  • 1Department of Neuroscience
  • The University of Osaka (JP)
Corresponding author
Sobue, Kenji
ORCID
Venue
The Journal of Cell Biology
Publisher
Rockefeller University Press
Published
2007-12-03
Volume
179
Issue
5
Pages
1027-1042
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
DOI
10.1083/jcb.200708174
PMC
PMC2099179
OpenAlex
W2139602514
Cited by
262
References
0
Citations by year
2026: 8 · 2025: 3 · 2024: 9 · 2023: 13 · 2022: 13 · 2021: 10 · 2020: 16 · 2019: 15 · 2018: 15 · 2017: 18 · 2016: 20 · 2015: 20 · 2014: 18 · 2013: 21 · 2012: 12
FWCI
4.50
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • The Journal of Cell Biology (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Kruppel-like factors research
Keywords
MRTF, MRTF-A, MRTF-B, epithelial-mesenchymal transition, TGF-β1 signaling, Smad3, actin cytoskeleton remodeling, serum response factor, nuclear translocation, fibrosis, tumor progression
MeSH terms
Snail Family Transcription Factors, Actins, Animals, Cytoskeleton, Dogs, Epithelial Cells, Gene Expression Regulation, Humans, Mesoderm, Promoter Regions, Genetic, Protein Binding, Subcellular Fractions, Transcription Factors, Protein Structure, Tertiary, rho GTP-Binding Proteins, Gene Expression Profiling, Protein Transport, Mice, Smad3 Protein, Transforming Growth Factor beta1

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