ArticleJournal of experimental & clinical cancer research : CR2021
Claudin-2 inhibits renal clear cell carcinoma progression by inhibiting YAP-activation.
Article in Journal of experimental & clinical cancer research : CR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- Circulating PDIA4, MMP-2, MMP-9, and Claudin-2 in Vitamin D-Deficient Patients with Brain Tumors: An Exploratory Clinical Pilot Study.Journal of clinical medicine · 2026Article
- The research trends and hotspots of claudins in the field of cancer.Cell adhesion & migration · 2025Review
- HnRNPR-mediated UPF3B mRNA splicing drives hepatocellular carcinoma metastasis.Journal of advanced research · 2025Article
- Claudin-12: guardian of the tissue barrier or friend of tumor cells.Tissue barriers · 2025Review
- Research progress of the Hippo signaling pathway in renal cell carcinoma.Asian journal of urology · 2024Review
- Review
- Expression and Targeted Application of Claudins Family in Hepatobiliary and Pancreatic Diseases.Journal of hepatocellular carcinoma · 2024Review
- Inflammatory Networks in Renal Cell Carcinoma.Cancers · 2023Review
- Claudin 4 enhances the malignancy of glioma cells via NNAT/Wnt signaling.American journal of cancer research · 2023Article
- Review
- The Regulation of the Hippo Pathway by Intercellular Junction Proteins.Life (Basel, Switzerland) · 2022Review
- The role and mechanism of claudins in cancer.Frontiers in oncology · 2022Review
- The critical role of the Hippo signaling pathway in kidney diseases.Frontiers in pharmacology · 2022Review
- Identification of a claudin-low subtype in clear cell renal cell carcinoma with implications for the evaluation of clinical outcomes and treatment efficacy.Frontiers in immunology · 2022Article
- Renal cell carcinoma-derived exosomes deliver lncARSR to induce macrophage polarization and promote tumor progression via STAT3 pathway.International journal of biological sciences · 2022Article
- Claudin-10 overexpression suppresses human clear cell renal cell carcinoma growth and metastasis by regulating ATP5O and causing mitochondrial dysfunction.International journal of biological sciences · 2022Article
- CLDN6 Suppresses c-MYC-Mediated Aerobic Glycolysis to Inhibit Proliferation by TAZ in Breast Cancer.International journal of molecular sciences · 2021Article
- Claudin-2 promotes colorectal cancer growth and metastasis by suppressing NDRG1 transcription.Clinical and translational medicine · 2021Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundClaudin-2 expression is upregulated in multiple cancers and promotes cancer malignancy. Remarkably, the regulation of claudin-2 expression in kidney cell lines contrasts its reported regulation in other organs. However, claudin-2 role in renal clear cell carcinoma (RCC) remains unknown despite its predominant expression in the proximal tubular epithelium (PTE), the site of RCC origin.
methodsPublicly available and independent patient databases were examined for claudin-2 association with RCC. The novel protein function was validated in vitro and in vivo by gain or loss of function assays. Mechanistic results were concluded by Mass spectroscopy, immunoprecipitation and mutational studies, and functional evaluations.
resultsWe show that the significant decrease in claudin-2 expression characterized PTE cells and Ex-vivo cultured mouse kidney subjected to dedifferentiation. Inhibition of claudin-2 was enough to induce mesenchymal plasticity and invasive mobility in these models. Further, a progressive loss of claudin-2 expression associated with the RCC progression and poor patient survival. Overexpression of claudin-2 in RCC-derived cancer cells inhibited tumorigenic abilities and xenograft tumor growth. These data supported a novel tumor-suppressive role of claudin-2 in RCC. Mechanistic insights further revealed that claudin-2 associates with YAP-protein and modulates its phosphorylation (S127) and nuclear expression. The tumor suppressive effects of claudin-2 expression were lost upon deletion of its PDZ-binding motif emphasizing the critical role of the PDZ-domain in claudin-2 interaction with YAP in regulating RCC malignancy.
conclusionsOur results demonstrate a novel kidney specific tumor suppressive role for claudin-2 protein and further demonstrate that claudin-2 co-operates with the YAP signaling in regulating the RCC malignancy.
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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.