ArticleCell death & disease2024
TRIM59/RBPJ positive feedback circuit confers gemcitabine resistance in pancreatic cancer by activating the Notch signaling pathway.
Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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The trial behind it
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Who cites it
9 citing papers in PubMed.
- TRIM59 Drives Bladder Cancer Progression Through E3 Ligase-Dependent K48-Linked Degradation of PTRF.Cancer science · 2026Article
- Targeting the Notch signaling pathway in digestive system cancers: from bench to bedside.Cancer cell international · 2026Review
- Cancer drug response and resistance: molecular mechanisms and combating strategies.Signal transduction and targeted therapy · 2026Review
- UCHL1 promotes temozolomide resistance in glioblastoma by inhibiting the ubiquitination-mediated degradation of keratin 8.Translational oncology · 2026Article
- TRIM59 promotes immune evasion and tumor progression in lung adenocarcinoma via ubiquitin- proteasomal degradation of IRF3.Frontiers in immunology · 2026Article
- NOTCH3 attenuates cytotoxicity via RBPJ-dependent PVR upregulation to influence immunotherapy outcomes in colorectal cancer.Frontiers in immunology · 2026Article
- Post-Translational Modifications: Key "Regulators" of Pancreatic Cancer Malignant Phenotype-Advances in Mechanisms and Targeted Therapies.Biomedicines · 2025Review
- Gemcitabine resistance by CITED4 upregulation via the regulation of BIRC2 expression in pancreatic cancer.Journal of biomedical science · 2025Article
- Role of Ubiquitin-regulated EMT in Cancer Metastasis and Chemoresistance.International journal of biological sciences · 2025Review
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Pancreatic cancer (PC) is one of the most lethal malignant tumors that lacks effective treatment, and gemcitabine-based chemoresistance occurs frequently. Therefore, new therapeutic strategies for PC are urgently needed. Tripartite motif containing 59 (TRIM59) plays an important role in breast and lung cancer chemoresistance. However, the association between TRIM59 and gemcitabine resistance in PC remains unclear. We identified TRIM59 as an innovative E3 ubiquitin ligase that activated Notch signaling in PC. TRIM59 levels were increased in PC and positively correlated with poor prognosis and gemcitabine resistance in PC patients. TRIM59 facilitated gemcitabine resistance in PC cells in vitro and in vivo. TRIM59 interacted with recombination signal binding protein for immunoglobulin kappa J region (RBPJ) and stabilized it by promoting K63-linked ubiquitination. RBPJ transcriptionally upregulated TRIM59 expression, forming a positive feedback loop with TRIM59. We identified a novel TRIM59 inhibitor, catechin, and confirmed that it sensitized PC cells to gemcitabine. TRIM59 conferred gemcitabine resistance in PC by promoting RBPJ K63-linked ubiquitination, followed by activating Notch signaling. Therefore, our study provides a promising target for gemcitabine sensitization in PC treatment.
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