ArticleJournal of experimental & clinical cancer research : CR2016
DNA methylation of claudin-6 promotes breast cancer cell migration and invasion by recruiting MeCP2 and deacetylating H3Ac and H4Ac.
Article in Journal of experimental & clinical cancer research : CR, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 74 citations in OpenAlex.
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- Mechanism of IL-4 mediated RPL19 promoting malignant progression in HER2 positive breast cancer.Breast cancer research : BCR · 2026Article
- Ethanol Alters DNMT1/3a/3b Expression Profile, Promotes Persistent DNA Hypomethylation in Human Brain Endothelial Cells and Impairs Late Cortical Angiogenesis.Journal of neurochemistry · 2026Article
- Oncofetal antigens as emerging targets in chimeric antigen receptor (CAR)-T cell-based immunotherapies: opportunities and challenges.Frontiers in cell and developmental biology · 2026Review
- Transcriptomic Association of COL3A1Pain research & management · 2026Article
- A Novel Tight Junction-Nuclear Receptor Signaling Pathway Regulating Cancer Progression.Pathology international · 2025Review
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- HBx Facilitates Drug Resistance in Hepatocellular Carcinoma via CD133-regulated Self-renewal of Liver Cancer Stem Cells.Journal of clinical and translational hepatology · 2025Article
- High-throughput methylation sequencing reveals novel biomarkers for the early detection of renal cell carcinoma.BMC cancer · 2025Article
- CLDN6 inhibits breast cancer growth and metastasis through SREBP1-mediated RAS palmitoylation.Cellular & molecular biology letters · 2024Article
- Epigenetic Modifiers in Cancer Metastasis.Biomolecules · 2024Review
- Expression patterns of claudins in cancer.Heliyon · 2023Review
- Binding of YY1/CREB to an Enhancer Region Triggers Claudin 6 Expression inInternational journal of molecular sciences · 2023Article
- The Epigenetic Reader Methyl-CpG-Binding Protein 2 (MeCP2) Is an Emerging Oncogene in Cancer Biology.Cancers · 2023Review
- Review
- Epigenomic reprogramming in iAs-mediated carcinogenesis.Advances in pharmacology (San Diego, Calif.) · 2023Article
- The expression and the tumor suppressor role of CLDN6 in colon cancer.Molecular and cellular biochemistry · 2022Article
- Article
- Estrogen Receptor and Claudin-6 Might Play Vital Roles for Long-Term Prognosis in Patients With Luminal A Breast Cancer Who Underwent Neoadjuvant Chemotherapy.Frontiers in oncology · 2022Article
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundClaudin-6 (CLDN6), a member of claudin transmembrane protein family, has recently been reported to be undetectable or at low levels in human breast cancer cell lines and tissues and plays a role in suppression of migration and invasion in breast cancer cells. In addition, it is reported that CLDN6 expression is regulated by DNA methylation in various human cancers and cell lines. However, it is unclear how DNA methylation regulates CLDN6 expression. Here we show the mechanism by which DNA methylation regulates CLDN6 expression in human breast cancer cell line MCF-7.
methodsRT-PCR, Western blot and immunofluorescent staining were utilized to investigate CLDN6 expression in breast cancer tissues and MCF-7 cells. Methylation-Specific PCR (MSP) was applied to determine DNA methylation status in CLDN6 gene promoter region. Wound-healing assay and invasion assay were utilized to test mobility of MCF-7 cells treated with 5-aza-dC (DNA methyltransferase inhibitor). MeCP2 binding, H3Ac and H4Ac in CLDN6 promoter region were analyzed by ChIP assay. Nuclease accessibility assay was performed for analysis of the chromatin conformation of CLDN6 gene. To study the role of CLDN6 in malignant progression, we used RNAi to knockdown CLDN6 expression in MCF-7 cells treated with 5-aza-dC, and examined the mobility of MCF-7 cells by wound-healing assay and invasion assay.
results5-aza-dC and TSA (histone deacetylase inhibitor) application induced CLDN6 expression in MCF-7 cells respectively and synergistically. 5-aza-dC treatment induced CLDN6 demethylation, inhibited MeCP2 binding to CLDN6 promoter and increased H3Ac and H4Ac in the promoter. In addition, TSA increased H4Ac, not H3Ac in the promoter. The chromatin structure of CLDN6 gene became looser than the control group after treating with 5-aza-dC in MCF-7 cells. 5-aza-dC up-regulated CLDN6 expression and suppressed migration and invasion in MCF-7 cells, whereas CLDN6 silence restored tumor malignance in MCF-7 cells.
conclusionsDNA methylation down-regulates CLDN6 expression through MeCP2 binding to the CLDN6 promoter, deacetylating H3 and H4, and altering chromatin structure, consequently promoting migratory and invasive phenotype in MCF-7 cells.
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