ArticlePloS one2014
SMAD4 regulates cell motility through transcription of N-cadherin in human pancreatic ductal epithelium.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 47 citations in OpenAlex.
- Article
- Histone acetyltransferase CSRP2BP promotes the epithelial-mesenchymal transition and metastasis of cervical cancer cells by activating N-cadherin.Journal of experimental & clinical cancer research : CR · 2023Article
- A pancreatic adenocarcinoma mimicking hepatoid carcinoma of uncertain histogenesis: A case report and literature review.Oncology letters · 2023Article
- YAP1 controls the N-cadherin-mediated tumor-stroma interaction in melanoma progression.Research square · 2023Article
- Histone Modifications Represent a Key Epigenetic Feature of Epithelial-to-Mesenchyme Transition in Pancreatic Cancer.International journal of molecular sciences · 2023Review
- Potential role of TGFΒ and autophagy in early crebellum development.Biochemistry and biophysics reports · 2022Article
- The Role ofCancers · 2022Review
- SMAD4 contributes to chondrocyte and osteocyte development.Journal of cellular and molecular medicine · 2022Review
- Article
- TGFβ Signaling in the Pancreatic Tumor Microenvironment.Cancers · 2021Review
- SMAD4 activates Wnt signaling pathway to inhibit granulosa cell apoptosis.Cell death & disease · 2020Article
- Antineoplastic effects of auranofin in human pancreatic adenocarcinoma preclinical models.Surgery open science · 2019Article
- Article
- Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Disulfiram combined with copper inhibits metastasis and epithelial-mesenchymal transition in hepatocellular carcinoma through the NF-κB and TGF-β pathways.Journal of cellular and molecular medicine · 2018Article
- TGF-β signaling controls FSHR signaling-reduced ovarian granulosa cell apoptosis through the SMAD4/miR-143 axis.Cell death & disease · 2016Article
- Transforming Growth Factor-β Limits Secretion of Lumican by Activated Stellate Cells within Primary Pancreatic Adenocarcinoma Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Article
- Activation of TGF-β1-CD147 positive feedback loop in hepatic stellate cells promotes liver fibrosis.Scientific reports · 2015Article
- Elevated GRP78 expression is associated with poor prognosis in patients with pancreatic cancer.Scientific reports · 2015Article
- SMAD4 and its role in pancreatic cancer.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Review
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Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
Abstract
Expression of the cellular adhesion protein N-cadherin is a critical event during epithelial-mesenchymal transition (EMT). The SMAD4 protein has been identified as a mediator of transforming growth factor-β (TGF-β) superfamily signaling, which regulates EMT, but the mechanisms linking TGF-β signaling to N-cadherin expression remain unclear. When the TGF-β pathway is activated, SMAD proteins, including the common mediator SMAD4, are subsequently translocated into the nucleus, where they influence gene transcription via SMAD binding elements (SBEs). Here we describe a mechanism for control of CDH2, the gene encoding N-cadherin, through the canonical TGFβ-SMAD4 pathway. We first identified four previously undescribed SBEs within the CDH2 promoter. Using telomerase immortalized human pancreatic ductal epithelium, we found that TGF-β stimulation prompted specific SMAD4 binding to all four SBEs. Luciferase reporter and SMAD4-knockdown experiments demonstrated that specific SMAD4 binding to the SBE located at -3790 bp to -3795 bp within the promoter region of CDH2 was necessary for TGF-β-stimulated transcription. Expression of N-cadherin on the surface of epithelial cells facilitates motility and invasion, and we demonstrated that knockdown of SMAD4 causes decreased N-cadherin expression, which results in diminished migration and invasion of human pancreatic ductal epithelial cells. Similar reduction of cell motility was produced after CDH2 knockdown. Together, these findings suggest that SMAD4 is critical for the TGF-β-driven upregulation of N-cadherin and the resultant invasive phenotype of human pancreatic ductal epithelial cells during EMT.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.