ArticleJCI insight2021
CMTM6 drives cisplatin resistance by regulating Wnt signaling through the ENO-1/AKT/GSK3β axis.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 55 citations in OpenAlex.
- Role of CMTM6 in disease pathogenesis and clinical translation potential (Review).Molecular medicine reports · 2026Review
- CMTM6 maintains B cell-intrinsic membrane CD40 stability to regulate anti-tumor immunity.Acta pharmaceutica Sinica. B · 2026Article
- ENO1 as an Immunoregulatory Hub in Cancer: Mechanisms and Translational Implications.Biomolecules · 2026Review
- Enolase 1: A paradigm of metabolic enzyme moonlighting in tumorigenesis (Review).International journal of oncology · 2026Review
- CMTM6 promotes synovial proliferation and macrophage polarization by preventing ubiquitination of TAK1 in rheumatoid arthritis.Journal of orthopaedic translation · 2026Article
- CMTM6/PD-L1-targeted AAV promotes anti-tumor immune responses and chemotherapy responsiveness.Frontiers in immunology · 2026Article
- RAS mutation status and immune microenvironment define distinct prognostic landscapes and predict chemotherapy benefit in pMMR colorectal cancer.Frontiers in immunology · 2026Article
- Identification and validation of key biomarkers for chemoresistance in oral squamous cell carcinoma.BMC cancer · 2025Article
- Metabolic enzyme-associated protein-protein interactions (mPPIs) in cancer: potential vulnerability for cancer treatment?Acta pharmacologica Sinica · 2025Review
- Graph attention networks-based prediction of MicroRNA-disease causality in head and neck neoplasms.Scientific reports · 2025Article
- PRELP regulated by GAS5/miR-3127-5p suppresses cisplatin resistance in oral squamous cell carcinoma.Cytotechnology · 2025Article
- Warburg effect and lactylation in cancer: mechanisms for chemoresistance.Molecular medicine (Cambridge, Mass.) · 2025Review
- WGCNA and ferroptosis genes in OSCC: unraveling prognostic biomarkers and therapeutic targets.Discover oncology · 2025Article
- Profiling genetic mutations in the DNA damage repair genes of oral squamous cell carcinoma patients from Pakistan.Scientific reports · 2025Article
- Dinaciclib Interrupts Cell Cycle and Induces Apoptosis in Oral Squamous Cell Carcinoma: Mechanistic Insights and Therapeutic Potential.International journal of molecular sciences · 2025Article
- Exploring the therapeutic potential of "Zhi-Zhen" formula for oxaliplatin resistance in colorectal cancer: an integrated study combining UPLC-QTOF-MS/MS, bioinformatics, network pharmacology, and experimental validation.Frontiers in medicine · 2025Article
- DLGAP5 enhances bladder cancer chemoresistance by regulating glycolysis through MYC stabilization.Theranostics · 2025Article
- Comprehensive analysis of CMTM family and immune infiltration in esophageal carcinoma.PloS one · 2025Article
- Gallic acid suppresses esophageal squamous cell carcinoma progression and enhances cisplatin chemosensitivity through IL-6/STAT3/Notch pathway.Oncology research · 2025Article
- The role and therapeutic potential of glucose metabolism in multidrug resistance of cancer.Frontiers in cell and developmental biology · 2025Review
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rewiring tumor cells to undergo drug-induced apoptosis is a promising way to overcome chemoresistance. Therefore, identifying causative factors for chemoresistance is of high importance. Unbiased global proteome profiling of sensitive, early, and late cisplatin-resistant oral squamous cell carcinoma (OSCC) lines identified CMTM6 as a top-ranked upregulated protein. Analyses of OSCC patient tumor samples demonstrated significantly higher CMTM6 expression in chemotherapy (CT) nonresponders as compared with CT responders. In addition, a significant association between higher CMTM6 expression and poorer relapse-free survival in esophageal squamous cell carcinoma, head and neck squamous cell carcinoma, and lung squamous cell carcinoma was observed from Kaplan-Meier plot analysis. Stable knockdown (KD) of CMTM6 restored cisplatin-mediated cell death in chemoresistant OSCC lines. Upon CMTM6 overexpression in CMTM6-KD lines, the cisplatin-resistant phenotype was rescued. The patient-derived cell xenograft model of chemoresistant OSCC displaying CMTM6 depletion restored the cisplatin-induced cell death and tumor burden substantially. The transcriptome analysis of CMTM6-KD and control chemoresistant cells depicted enrichment of the Wnt signaling pathway. We demonstrated that CMTM6 interaction with membrane-bound Enolase-1 stabilized its expression, leading to activation of Wnt signaling mediated by AKT-glycogen synthase kinase-3β. CMTM6 has been identified as a stabilizer of programmed cell death ligand 1. Therefore, as CMTM6 facilitates tumor cells for immune evasion and mediates cisplatin resistance, it could be a promising therapeutic target for treating therapy-resistant OSCC.
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