A SNAIL1–SMAD3/4 transcriptional repressor complex promotes TGF-β mediated epithelial–mesenchymal transition

@article{Vincent2009AST,
  title={A SNAIL1–SMAD3/4 transcriptional repressor complex promotes TGF-$\beta$ mediated epithelial–mesenchymal transition},
  author={Theresa Vincent and Etienne P. A. Neve and Jill R. Johnson and Alexander Kukalev and Federico Rojo and Joan Albanell and Kristian Pietras and Ismo Virtanen and L. Philipson and Philip L. Leopold and Ronald G. Crystal and Antonio Garc{\'i}a de Herreros and Aristidis Moustakas and RALF F. Pettersson and Jonas Fuxe},
  journal={Nature Cell Biology},
  year={2009},
  volume={11},
  pages={943-950}
}
Epithelial–mesenchymal transition (EMT) is essential for organogenesis and is triggered during carcinoma progression to an invasive state. Transforming growth factor-β (TGF-β) cooperates with signalling pathways, such as Ras and Wnt, to induce EMT, but the molecular mechanisms are not clear. Here, we report that SMAD3 and SMAD4 interact and form a complex with SNAIL1, a transcriptional repressor and promoter of EMT. The SNAIL1–SMAD3/4 complex was targeted to the gene promoters of CAR, a tight… Expand
JAK/STAT3 signaling is required for TGF-β-induced epithelial-mesenchymal transition in lung cancer cells.
TLDR
The findings show that the JAK/ STAT3 pathway is required for TGF-β-induced EMT and cancer cell migration and invasion via upregulation of the expression of p-Smad3 and Snail, and the IL-6/JAK/STAT3 and T GF-β/Smad signaling synergistically enhance EMT in lung carcinomas. Expand
JAK / STAT 3 signaling is required for TGF-β-induced epithelial-mesenchymal transition in lung cancer cells
Epithelial-mesenchymal transition (EMT), a key step in the early stages of cancer metastasis, is orchestrated by several signaling pathways, including IL-6/JAK/STAT3 and TGF-β/Smad signaling.Expand
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TLDR
EGCG inhibits TGF-β1-mediated EMT by suppressing the acetylation of Smad2 and Smad3 in human lung cancer cells by inhibiting the induction of p300/CBP activity by TGF -β1. Expand
The Role of Snail in EMT and Tumorigenesis.
TLDR
Emerging evidences indicate that Snail causes a metabolic reprogramming, bestows tumor cells with cancer stem cell-like traits, and additionally, promotes drug resistance, tumor recurrence and metastasis. Expand
Repression of Smad4 by miR‑205 moderates TGF-β-induced epithelial-mesenchymal transition in A549 cell lines.
TLDR
It is confirmed that overexpression of miR‑205 suppressed the expression of Smad4, in turn, weakened the TGF-β/Smad signaling pathway and inhibited TGF+Smad4-induced EMT, invasion and migration ultimately and shows that miR‐205 can serve as a promising therapeutic target of highly aggressive NSCLC. Expand
Smad4 and epithelial–mesenchymal transition proteins in colorectal carcinoma: an immunohistochemical study
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Smad4 could be considered as a central component of EMT transition in human colorectal cancer that combines with transcriptional factors to reduce E-cadherin and alter the expression of the epithelial phenotype. Expand
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TLDR
Current understanding of the mechanisms involved in the transcriptional crosstalk between TGF-β and stem cell pathways are reviewed and how a fundament for the activation of these mechanisms may lead to the induction of EMT in tumors is discussed. Expand
TGF-β-activated SMAD3/4 complex transcriptionally upregulates N-cadherin expression in non-small cell lung cancer.
TLDR
It is found that TGF-β-activated SMAD3/4 complex may upregulateCDH2 expression by directly interacting with a specific SMAD-binding element in CDH2 promoter. Expand
Targeted DNA oxidation by LSD1–SMAD2/3 primes TGF-β1/ EMT genes for activation or repression
TLDR
These data elucidate the early events elicited by TGF-β1 and the priming role of DNA oxidation that marks TGF -β1-induced and -repressed genes involved in the EMT. Expand
STAT3 aggravates TGF-β1-induced hepatic epithelial-to-mesenchymal transition and migration.
  • Bin Wang, Ting Liu, +4 authors M. Xu
  • Chemistry, Medicine
  • Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
  • 2018
TLDR
Investigation of the underlying molecular mechanisms of STAT3 crosstalk with Snail-Smad3/transforming growth factor (TGF)-β1 signaling pathways during the EMT in hepatocellular carcinoma (HCC) finds STAT3 functions as a positive regulator to activate TGF-β1-induced EMT and metastasis of HCC. Expand
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References

SHOWING 1-10 OF 41 REFERENCES
Differential Regulation of Epithelial and Mesenchymal Markers by δEF1 Proteins in Epithelial–Mesenchymal Transition Induced by TGF-β
TLDR
It is suggested that the δEF1 family proteins, SIP1 and δ EF1, are necessary, but not sufficient, for TGF-β–induced EMT and that Ets1 induced by T GF-β may function as an upstream transcriptional regulator of SIP2 and εEF1. Expand
Dual regulation of Snail by GSK-3β-mediated phosphorylation in control of epithelial–mesenchymal transition
TLDR
It is shown that GSK-3β binds to and phosphorylates Snail at two consensus motifs to dually regulate the function of this protein and together function as a molecular switch for many signalling pathways that lead to EMT. Expand
The transcription factor Snail controls epithelial–mesenchymal transitions by repressing E-cadherin expression
TLDR
It is shown that mouse Snail is a strong repressor of transcription of the E-cadherin gene, opening up new avenues for the design of specific anti-invasive drugs. Expand
A Wnt–Axin2–GSK3β cascade regulates Snail1 activity in breast cancer cells
TLDR
It is demonstrated that canonical Wnt signalling engages tumour cell dedifferentiation and tissue-invasive activity through an Axin2-dependent pathway that stabilizes the Snail1 zinc-transcription factor, a key regulator of normal and neoplastic EMT programmes. Expand
Role of Smad Proteins and Transcription Factor Sp1 in p21Waf1/Cip1 Regulation by Transforming Growth Factor-β*
TLDR
Smad proteins play important roles in regulation of the p21 gene by TGF-β, and the functional cooperation of Smad proteins with Sp1 involves the physical interaction of these two types of transcription factors. Expand
TGFβ3 inhibits E-cadherin gene expression in palate medial-edge epithelial cells through a Smad2-Smad4-LEF1 transcription complex
TLDR
It is proved that TGFβ3 signaling induces EMT in MEE cells by forming activated transcription complexes of Smad2-P, Smad4 and LEF1 that directly inhibit E-cadherin gene expression. Expand
Transforming Growth Factor-β Signaling during Epithelial-Mesenchymal Transformation: Implications for Embryogenesis and Tumor Metastasis
TLDR
The biochemical signaling pathways of TGF-β and their potential cross-interaction with traditional Wnt signaling molecules to bring about EMT during embryogenesis and tumor metastasis are assessed. Expand
Regulation of tight junctions during the epithelium-mesenchyme transition: direct repression of the gene expression of claudins/occludin by Snail
TLDR
EMT was associated with the simultaneous repression of the genes encoding E-cadherin and claudins/occludin (i.e. the expression of adherens and tight junction adhesion molecules, respectively). Expand
Transforming Growth Factor-β Receptor Inhibition Enhances Adenoviral Infectability of Carcinoma Cells via Up-Regulation of Coxsackie and Adenovirus Receptor in Conjunction with Reversal of Epithelial-Mesenchymal Transition
TLDR
Findings show down-regulation of CAR in the context of EMT and suggest that combination of therapeutic adenoviruses and TGF-β receptor inhibitors could be an efficient anticancer strategy. Expand
Ras and TGFβ cooperatively regulate epithelial cell plasticity and metastasis
TLDR
EMT seems to be a close in vitro correlate of metastasis, both requiring synergism between TGFβ-R and Raf/MAPK signaling and a hyperactive Raf/mitogen-activated protein kinase (MAPK) is required for EMT. Expand
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