ArticleCancer letters2023
Claudin-1 interacts with EPHA2 to promote cancer stemness and chemoresistance in colorectal cancer.
Article in Cancer letters, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 46 citations in OpenAlex.
- Mechanisms and advances of drug resistance in colorectal cancer: A systematic overview of multi-layered regulatory networks.Translational oncology · 2026Review
- Primary cilia connect epithelial mesenchymal plasticity with anoikis resistance and cancer stemness.Discover oncology · 2026Review
- Structure-forward targeting of claudins with synthetic binders.FEBS letters · 2026Review
- EphA2/SHP2/SOX8 Axis: A Novel Target for Regulation of Migration and Cetuximab Treatment Sensitivity in Oral Squamous Cell Carcinoma.Molecular carcinogenesis · 2026Article
- The YAP1 and EPHA3 receptor tyrosine kinase axis regulates cellular plasticity and treatment response.Cellular signalling · 2026Article
- Claudin proteins as emerging therapeutic targets for solid tumours.Nature reviews. Cancer · 2026Review
- Establishment and validation of a novel anoikis-related prognostic signature of lung squamous cell carcinoma.Translational cancer research · 2026Article
- Article
- Prognostic prediction and immune microenvironment analysis in colorectal cancer using exosome-related lncRNA signatures.Discover oncology · 2026Article
- Screening and validation of potential molecular markers for colorectal cancer: based on bioinformatics analysis and machine learning.Clinical and experimental medicine · 2026Article
- A Claudin-1 Near-Infrared Fluorescent Antibody Conjugate for In Vivo Primary and Metastatic Colorectal Cancer Detection.Molecular imaging and biology · 2026Article
- Claudin-1 Interacts with CD81 and Promotes the Progression of Colorectal Cancer.Oncology research · 2026Article
- Resistance mechanisms and countermeasures in CLDN18.2-positive tumors: from molecular networks to clinical practice.Frontiers in oncology · 2026Review
- Single-Cell and Multi-Omics-Based Characterization of Gastric Cancer Identifies TPP1 as a Potential Target for Gastric Cancer Progression and Treatment.Oncology research · 2026Article
- Roles of anoikis in hepatocellular carcinoma therapy and the assessment of anoikis-regulatory molecules as therapeutic targets.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Claudin-1 Contributes to Gastrointestinal Stromal Tumors (GIST) Resistance to Imatinib Mesylate (IM) via Regulation of FGFR-Signaling.International journal of molecular sciences · 2025Article
- Development of an Anti-CD99 Antibody Enables Targeting of Diffuse Midline Glioma.Cancer research · 2025Article
- EPS8L2 drives colorectal cancer cell proliferation and migration via YBX1-dependent activation of G3BP2 transcription.Cell death & disease · 2025Article
- Anoikis resistance in Cancer: Mechanisms, therapeutic strategies, potential targets, and models for enhanced understanding.Cancer letters · 2025Review
- Epithelial-mesenchymal transition in colorectal cancer metastasis and progression: molecular mechanisms and therapeutic strategies.Cell death discovery · 2025Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Therapy resistance is the primary problem in treating late-stage colorectal cancer (CRC). Claudins are frequently dysregulated in cancer, and several are being investigated as novel therapeutic targets and biomarkers. We have previously demonstrated that Claudin-1 (CLDN1) expression in CRC promotes epithelial-mesenchymal transition, metastasis, and resistance to anoikis. Here, we hypothesize that CLDN1 promotes cancer stemness and chemoresistance in CRC. We found that high CLDN1 expression in CRC is associated with cancer stemness and chemoresistance signaling pathways in patient datasets, and it promotes chemoresistance both in vitro and in vivo. Using functional stemness assays, proteomics, biophysical binding assays, and patient-derived organoids, we found that CLDN1 promotes properties of cancer stemness including CD44 expression, tumor-initiating potential, and chemoresistance through a direct interaction with ephrin type-A receptor 2 (EPHA2) tyrosine kinase. This interaction is dependent on the CLDN1 PDZ-binding motif, increases EPHA2 protein expression by inhibiting its degradation, and enhances downstream AKT signaling and CD44 expression to promote stemness and chemoresistance. These results suggest CLDN1 is a viable target for pharmacological intervention and/or biomarker development.
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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.