ArticleOncogene2022
CRISPR-based kinome-screening revealed MINK1 as a druggable player to rewire 5FU-resistance in OSCC through AKT/MDM2/p53 axis.
Article in Oncogene, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- NEK9-mediated Wnt signalling repressor TLE3 rewires Docetaxel resistance in cancer cells by inducing pyroptosis.British journal of cancer · 2025Article
- Decoding NLRP3 Inflammasome Activation in Alzheimer's Disease: A Focus on Receptor Dynamics.Molecular neurobiology · 2025Review
- The CRISPR-Cas revolution in head and neck cancer: a new era of targeted therapy.Functional & integrative genomics · 2025Review
- Dinaciclib Interrupts Cell Cycle and Induces Apoptosis in Oral Squamous Cell Carcinoma: Mechanistic Insights and Therapeutic Potential.International journal of molecular sciences · 2025Article
- Integrative multi-omics analysis and experimental validation identify molecular subtypes, prognostic signature, and CA9 as a therapeutic target in oral squamous cell carcinoma.Frontiers in cell and developmental biology · 2025Article
- Longikaurin A, a natural ent-kaurane, suppresses proliferation, invasion and tumorigenicity in oral squamous cell carcinoma cell by via inhibiting PI3K/Akt pathwayJournal of Cancer · 2025Article
- Resveratrol contributes to NK cell-mediated breast cancer cytotoxicity by upregulating ULBP2 through miR-17-5p downmodulation and activation of MINK1/JNK/c-Jun signaling.Frontiers in immunology · 2025Article
- Acetyltransferase NAT10 promotes an immunosuppressive microenvironment by modulating CD8Molecular biomedicine · 2024Article
- Clinical Potential of Misshapen/NIKs-Related Kinase (MINK) 1-A Many-Sided Element of Cell Physiology and Pathology.Current issues in molecular biology · 2024Review
- The role of prickle proteins in vertebrate development and pathology.Molecular and cellular biochemistry · 2024Review
- Head and neck cancer care: advanced molecular and genetic diagnostics.EXCLI journal · 2024Article
- Proximal TubularInternational journal of molecular sciences · 2023Article
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11 authors.
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Abstract
Cisplatin, 5FU and docetaxel (TPF) are the most common chemotherapy regimen used for advanced OSCC. However, many cancer patients experience relapse, continued tumor growth, and spread due to drug resistance, which leads to treatment failure and metastatic disease. Here, using a CRISPR/Cas9 based kinome knockout screening, Misshapen-like kinase 1 (MINK1) is identified as an important mediator of 5FU resistance in OSCC. Analysis of clinical samples demonstrated significantly higher MINK1 expression in the tumor tissues of chemotherapy non-responders as compared to chemotherapy responders. The nude mice and zebrafish xenograft experiments indicate that knocking out MINK1 restores 5FU mediated cell death in chemoresistant OSCC. An antibody based phosphorylation array screen revealed MINK1 as a negative regulator of p53. Mechanistically, MINK1 modulates AKT phosphorylation at Ser473, which enables p-MDM2 (Ser 166) mediated degradation of p53. We also identified lestaurtinib as a potent inhibitor of MINK1 kinase activity. The patient derived TPF resistant cell based xenograft data suggest that lestaurtinib restores 5FU sensitivity and facilitates a significant reduction of tumor burden. Overall, our study suggests that MINK1 is a major driver of 5FU resistance in OSCC. The novel combination of MINK1 inhibitor lestaurtinib and 5FU needs further clinical investigation in advanced OSCC.
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