ArticleInternational journal of molecular sciences2017
SMAD2 Inactivation Inhibits CLDN6 Methylation to Suppress Migration and Invasion of Breast Cancer Cells.
Article in International journal of molecular sciences, 2017. 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, 29 citations in OpenAlex.
- Involvement of claudins 6 and 9 in epithelial-mesenchymal transition and the metastatic process.Tissue barriers · 2026Review
- Vitamin D alleviates HFD-induced hepatic fibrosis by inhibiting DNMT1 to affect the TGFβ1/Smad3 pathway.iScience · 2024Article
- Expression patterns of claudins in cancer.Heliyon · 2023Review
- Review
- CLDN6 Suppresses Migration and Invasion of MCF-7 and SKBR-3 Breast Cancer Cells by Blocking the SMAD/Snail/MMP-2/9 Axis.Bulletin of experimental biology and medicine · 2023Article
- Review
- Research progress of Claudin-low breast cancer.Frontiers in oncology · 2023Review
- The role and mechanism of claudins in cancer.Frontiers in oncology · 2022Review
- Transforming growth factor-β in tumour development.Frontiers in molecular biosciences · 2022Review
- CLDN6: From Traditional Barrier Function to Emerging Roles in Cancers.International journal of molecular sciences · 2021Review
- Claudin 6: Therapeutic prospects for tumours, and mechanisms of expression and regulation (Review).Molecular medicine reports · 2021Review
- Identification of Claudin-6 as a Molecular Biomarker in Pan-Cancer Through Multiple Omics Integrative Analysis.Frontiers in cell and developmental biology · 2021Article
- The Expression of CLDN6 in Hepatocellular Carcinoma Tissue and the Effects of CLDN6 on Biological Phenotypes of Hepatocellular Carcinoma Cells.Journal of Cancer · 2021Article
- MicroRNA-27a inhibits trophoblast cell migration and invasion by targeting SMAD2: Potential role in preeclampsia.Experimental and therapeutic medicine · 2020Article
- Review
- CLDN6-mediates SB431542 action through MMPs to regulate the invasion, migration, and EMT of breast cancer cells.International journal of clinical and experimental pathology · 2020Article
- DOCK1 Regulates Growth and Motility through the RRP1B-Claudin-1 Pathway in Claudin-Low Breast Cancer Cells.Cancers · 2019Article
- Estrogen receptor β inhibits breast cancer cells migration and invasion through CLDN6-mediated autophagy.Journal of experimental & clinical cancer research : CR · 2019Article
- Bone Metastasis Phenotype and Growth Undergo Regulation by Micro-Environment Stimuli: Efficacy of Early Therapy with HGF or TGFβ1-Type I Receptor Blockade.International journal of molecular sciences · 2019Article
- Knockdown of CLDN6 inhibits cell proliferation and migration via PI3K/AKT/mTOR signaling pathway in endometrial carcinoma cell line HEC-1-B.OncoTargets and therapy · 2018Article
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The downregulation of tight junction protein CLDN6 promotes breast cancer cell migration and invasion; however, the exact mechanism underlying CLDN6 downregulation remains unclear. CLDN6 silence is associated with DNA methyltransferase 1 (DNMT1) mediated DNA methylation, and DNMT1 is regulated by the transforming growth factor beta (TGFβ)/SMAD pathway. Therefore, we hypothesized that TGFβ/SMAD pathway, specifically SMAD2, may play a critical role for CLDN6 downregulation through DNA methyltransferase 1 (DNMT1) mediated DNA methylation. To test this hypothesis, we blocked the SMAD2 pathway with SB431542 in two human breast cancer cell lines (MCF-7 and SKBR-3). Our results showed that treatment with SB431542 led to a decrease of DNMT1 expression and the binding activity for CLDN6 promoter. The methylation level of CLDN6 promoter was decreased, and simultaneously CLDN6 protein expression increased. Upregulation of CLDN6 inhibited epithelial to mesenchymal transition (EMT) and reduced the migration and invasion ability of both MCF-7 and SKBR-3 cells. Furthermore, knocked down of CLDN6 abolished SB431542 effects on suppression of EMT associated gene expression and inhibition of migration and invasion. Thus, we demonstrated that the downregulation of CLDN6 is regulated through promoter methylation by DNMT1, which depends on the SMAD2 pathway, and that CLDN6 is a key regulator in the SMAD2/DNMT1/CLDN6 pathway to inhibit EMT, migration and invasion of breast cancer cells.
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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.