ArticlePloS one2012
Caudal homeobox protein Cdx-2 cooperates with Wnt pathway to regulate claudin-1 expression in colon cancer cells.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 70 citations in OpenAlex.
- Reproducible processing of TCGA regulatory networks.GigaScience · 2025Article
- Near-Infrared In Vivo Imaging of Claudin-1 Expression by Orthotopically Implanted Patient-Derived Colonic Adenoma Organoids.Diagnostics (Basel, Switzerland) · 2024Article
- Expression patterns of claudins in cancer.Heliyon · 2023Review
- Tight Junction Claudins and Occludin Are Differentially Regulated and Expressed in Genomically Defined Subsets of Colon Cancer.Current issues in molecular biology · 2023Article
- Functions of the RIP kinase family members in the skin.Cellular and molecular life sciences : CMLS · 2023Review
- Article
- Negative elongation factor: a key factor in the maintenance of intestinal epithelial barrier integrity.Cellular & molecular immunology · 2022Article
- The role and mechanism of claudins in cancer.Frontiers in oncology · 2022Review
- CDX2 as a Predictive Biomarker Involved in Immunotherapy Response Suppresses Metastasis through EMT in Colorectal Cancer.Disease markers · 2022Article
- Resveratrol Downregulates miR-155-5p to Block the Malignant Behavior of Gastric Cancer Cells.BioMed research international · 2022Article
- Dysregulated expression of claudins in cancer.Oncology letters · 2021Review
- Epigenetic Regulation of Claudin-1 in the Development of Ovarian Cancer Recurrence and Drug Resistance.Frontiers in oncology · 2021Article
- CDX2 inhibits epithelial-mesenchymal transition in colorectal cancer by modulation of Snail expression and β-catenin stabilisation via transactivation of PTEN expression.British journal of cancer · 2021Article
- Claudin-1, A Double-Edged Sword in Cancer.International journal of molecular sciences · 2020Review
- Role of Claudin Proteins in Regulating Cancer Stem Cells and Chemoresistance-Potential Implication in Disease Prognosis and Therapy.International journal of molecular sciences · 2019Review
- Differential Expression Pattern of Epithelial Mesenchymal Transition Gens: AXL, GAS6, Claudin-1, and Cofilin-1, in Different Stages of Epithelial Ovarian Cancer.Iranian journal of public health · 2019Article
- Cocaine Induces Inflammatory Gut Milieu by Compromising the Mucosal Barrier Integrity and Altering the Gut Microbiota Colonization.Scientific reports · 2019Article
- Prognostic Role of Claudin-1 Immunohistochemistry in Malignant Solid Tumors: A Meta-Analysis.Journal of pathology and translational medicine · 2019Article
- Review
- Claudin Family Participates in the Pathogenesis of Inflammatory Bowel Diseases and Colitis-Associated Colorectal Cancer.Frontiers in immunology · 2019Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Dysregulation of tight junctions (TJs) is often associated with human diseases including carcinogenesis and recent studies support role of TJ integral proteins in the regulation of Epithelial-to-Mesenchymal Transition (EMT). In this regard, expression of claudin-1, a key constituent of TJs, is highly increased in colon cancer and is causally associated with the tumor growth and progression. However, mechanism/s underlying regulation of claudin-1 expression in intestinal epithelial cells remains poorly understood. In our studies, we have identified putative binding sites for intestinal transcription factors Cdx1, -2 and GATA4 in the 5'-flanking region of the claudin-1 gene. Our further studies using full length and/or deletion mutant constructs in two different human colon cancer cell lines, SW480 and HCT116, showed key role of Cdx1, Cdx2 and GATA4 in the regulation of claudin-1 mRNA expression. However, overexpression of Cdx2 had the most potent effect upon claudin-1 mRNA expression and promoter activity. Also, in colon cancer patient samples, we observed a significant and parallel correlation between claudin-1 and Cdx2 expressions. Chromatin immunoprecipitation (ChIP) assay confirmed the Cdx2 binding with claudin-1 promoter in vivo. Using Cdx2 deletion mutant constructs, we further mapped the Cdx2 C-terminus domain to be important in the regulation of claudin-1 promoter activity. Interestingly, co-expression of activated β-catenin further induced the Cdx2-dependent upregulation of claudin-1 promoter activity while expression of the dominant negative (dn)-TCF-4 abrogated this activation. Taken together, we conclude that homeodomain transcription factors Cdx1, Cdx2 and GATA4 regulate claudin-1 gene expression in human colon cancer cells. Moreover, a functional crosstalk between Wnt-signaling and transcriptional activation related to caudal-related homeobox (Cdx) proteins and GATA-proteins is demonstrated in the regulation of claudin-1 promoter-activation.
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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.