ArticleOncogene2017
Loss of claudin-3 expression induces IL6/gp130/Stat3 signaling to promote colon cancer malignancy by hyperactivating Wnt/β-catenin signaling.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
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Who cites it
89 citing papers in PubMed, 125 citations in OpenAlex.
- Trial
- Tight junction dysfunction and cytoskeletal remodeling in Hirschsprung‑associated enterocolitis: A decade of mechanistic insights and therapeutic prospects (Review).Molecular medicine reports · 2026Review
- Across Barriers: Blood-Brain and Gut Barrier Signaling in Psychiatric Disorders.Journal of neurochemistry · 2025Review
- PTEN Inactivation in Mouse Colonic Epithelial Cells Curtails DSS-Induced Colitis and Accelerates Recovery.Cancers · 2025Article
- Evaluation of Intestinal Permeability in Children Diagnosed With Bronchiolitis in Pediatric Emergency Department: A Cross-Sectional Study.Pediatric pulmonology · 2025Article
- Decoding the Tumor-Associated Microbiota: From Origins to Nanomedicine Applications in Cancer Therapy.Biology · 2025Review
- Guts for Self-Eating: Role of Autophagy in Gastrointestinal Health and Disease.Gastro hep advances · 2025Review
- Probing the Depths of Molecular Complexity: STAT3 as a Key Architect in Colorectal Cancer Pathogenesis.Current gene therapy · 2025Review
- Prevalence and clinical significance of Claudin-3 expression in cancer: a tissue microarray study on 14,966 tumor samples.Biomarker research · 2024Article
- IL-22 regulates MASTL expression in intestinal epithelial cells.American journal of physiology. Gastrointestinal and liver physiology · 2024Article
- A Review of the Use of Native and Engineered Probiotics for Colorectal Cancer Therapy.International journal of molecular sciences · 2024Review
- Activated fibroblasts modify keratinocyte stem niche through TET1 and IL-6 to promote their rapid transformation in a mouse model of prenatal arsenic exposure.Scientific reports · 2024Article
- The Expression of the Claudin Family of Proteins in Colorectal Cancer.Biomolecules · 2024Review
- Claudins: from gatekeepers of epithelial integrity to potential targets in hepato-pancreato-biliary cancers.Frontiers in oncology · 2024Review
- Article
- Claudin-2 protects against colitis-associated cancer by promoting colitis-associated mucosal healing.The Journal of clinical investigation · 2023Article
- Expression patterns of claudins in cancer.Heliyon · 2023Review
- Repeated Social Defeat Stress Induces an Inflammatory Gut Milieu by Altering the Mucosal Barrier Integrity and Gut Microbiota Homeostasis.Biological psychiatry global open science · 2023Article
- Exploring the complex role of gut microbiome in the development of precision medicine strategies for targeting microbial imbalance-induced colon cancer.Folia microbiologica · 2023Review
- Preliminary study on the mechanism of POFUT1 in colorectal cancer.Medical oncology (Northwood, London, England) · 2023Article
29 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 3 countries.
Funding
Abstract
The hyperactivated Wnt/β-catenin signaling acts as a switch to induce epithelial to mesenchymal transition and promote colorectal cancer. However, due to its essential role in gut homeostasis, therapeutic targeting of this pathway has proven challenging. Additionally, IL-6/Stat-3 signaling, activated by microbial translocation through the dysregulated mucosal barrier in colon adenomas, facilitates the adenoma to adenocarcinomas transition. However, inter-dependence between these signaling pathways and key mucosal barrier components in regulating colon tumorigenesis and cancer progression remains unclear. In current study, we have discovered, using a comprehensive investigative regimen, a novel and tissue-specific role of claudin-3, a tight junction integral protein, in inhibiting colon cancer progression by serving as the common rheostat of Stat-3 and Wnt-signaling activation. Loss of claudin-3 also predicted poor patient survival. These findings however contrasted an upregulated claudin-3 expression in other cancer types and implicated role of the epigenetic regulation. Claudin-3-/- mice revealed dedifferentiated and leaky colonic epithelium, and developed invasive adenocarcinoma when subjected to colon cancer. Wnt-signaling hyperactivation, albeit in GSK-3β independent manner, differentiated colon cancer in claudin-3-/- mice versus WT-mice. Claudin-3 loss also upregulated the gp130/IL6/Stat3 signaling in colonic epithelium potentially assisted by infiltrating immune components. Genetic and pharmacological studies confirmed that claudin-3 loss induces Wnt/β-catenin activation, which is further exacerbated by Stat-3-activation and help promote colon cancer. Overall, these novel findings identify claudin-3 as a therapeutic target for inhibiting overactivation of Wnt-signaling to prevent CRC malignancy.
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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.