ArticleBritish journal of cancer2024
TRIM21/USP15 balances ACSL4 stability and the imatinib resistance of gastrointestinal stromal tumors.
Article in British journal of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 17 citations in OpenAlex.
- Post-translational modifications in metabolic reprogramming: implications for metabolic therapy and immunotherapy in cancer.Signal transduction and targeted therapy · 2026Review
- eIF3 musketeers: loyal in health, rogue in disease, and redeemed by therapeutic targeting.The EMBO journal · 2026Review
- Targeting the FTO-ACSL4 Pathway: A Novel Mechanism for Sanguinarine Chloride-Induced Ferroptosis in Endometrial Cancer.Biomedicines · 2026Article
- The multifaceted roles of the ACSL family in cancer: Metabolic reprogramming, ferroptosis regulation and tumour immune microenvironment remodelling.Clinical and translational medicine · 2026Review
- Molecular Mechanisms and Clinical Implications ofCurrent issues in molecular biology · 2025Review
- β-elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1.Clinical and translational medicine · 2025Article
- Tyrosine Kinase Inhibitors for Gastrointestinal Stromal Tumor After Imatinib Resistance.Pharmaceutics · 2025Review
- The E3 Ubiquitin Ligase ARIH1 Facilitates Colorectal Cancer Progression by Promoting Oxidative Phosphorylation via the Mitochondrial Translocation of K63-Linked Ubiquitinated PHB1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- TRIM21 Promotes Tumor Growth and Gemcitabine Resistance in Pancreatic Cancer by Inhibiting EPHX1-Mediated Arachidonic Acid Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The effect of ubiquitination and deubiquitination to imatinib resistance in gastrointestinal stromal tumors.Frontiers in oncology · 2025Review
- TRIM21: a multifaceted regulator in cancer.Frontiers in cell and developmental biology · 2025Review
- Deubiquitinating enzymes: Key regulators of ferroptosis and pyroptosis and novel targets for cancer intervention.International journal of biological sciences · 2025Review
- The deubiquitinase USP15 drives malignant progression of gastric cancer through glucose metabolism remodeling.Journal of experimental & clinical cancer research : CR · 2024Article
- Targeting ferroptosis as a potential strategy to overcome the resistance of cisplatin in oral squamous cell carcinoma.Frontiers in pharmacology · 2024Review
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundImatinib has become an exceptionally effective targeted drug for treating gastrointestinal stromal tumors (GISTs). Despite its efficacy, the resistance to imatinib is common in GIST patients, posing a significant challenge to the effective treatment.
methodsThe expression profiling of TRIM21, USP15, and ACSL4 in GIST patients was evaluated using Western blot and immunohistochemistry. To silence gene expression, shRNA was utilized. Biological function of TRIM21, USP15, and ACSL4 was examined through various methods, including resistance index calculation, colony formation, shRNA interference, and xenograft mouse model. The molecular mechanism of TRIM21 and USP15 in GIST was determined by conducting Western blot, co-immunoprecipitation, and quantitative real-time PCR (qPCR) analyses.
resultsHere we demonstrated that downregulation of ACSL4 is associated with imatinib (IM) resistance in GIST. Moreover, clinical data showed that higher levels of ACSL4 expression are positively correlated with favorable clinical outcomes. Mechanistic investigations further indicated that the reduced expression of ACSL4 in GIST is attributed to excessive protein degradation mediated by the E3 ligase TRIM21 and the deubiquitinase USP15.
conclusionThese findings demonstrate that the TRIM21 and USP15 control ACSL4 stability to maintain the IM sensitive/resistant status of GIST.
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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.