ArticleCell death & disease2024
Targeting TRAF6/IRF3 axis to inhibit NF-κB-p65 nuclear translocation enhances the chemosensitivity of 5-FU and reverses the proliferation of gastric cancer.
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 15 papers.
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Who cites it
15 citing papers in PubMed.
- CXCL11 secreted by cancer-associated fibroblasts promotes nasopharyngeal carcinoma progression via CXCR3/PD-L1 axis.Cell adhesion & migration · 2026Article
- The miR-302 family suppresses tumor growth in tongue squamous cell carcinoma by directly targeting P65.Oncogene · 2026Article
- Blockage of cuproplasia inhibits pancreatic tumour-associated neutrophils infiltration through TRAF6/STAT3/CCL2 pathway.British journal of cancer · 2026Article
- Dietary Polyphenols as Natural Modulators of NF-κB Signaling in Inflammation-Driven Non-Communicable Diseases: Focus on Cancer.Food science & nutrition · 2026Review
- Neural Crest-Derived Stem Cell Secretomes and Extracellular Vesicles Disrupt Glioblastoma through Dual-Pathway Inflammatory Rebalancing.Stem cell reviews and reports · 2026Article
- Review
- miRNA-146b TargetsAnimals : an open access journal from MDPI · 2026Article
- E3 ubiquitin ligases orchestrate chemo-resistance in gastrointestinal malignancies: from DNA damage response to therapeutic targeting.Frontiers in oncology · 2026Review
- Diabetic Kidney Disease Progression Alleviated in Mice by ALKBH5-Mediated UC-MSCs-Derived Exosomes That Inhibit TRAF6 m6A Modification and Promote M2 Macrophage Polarisation.Endocrinology, diabetes & metabolism · 2026Article
- From Antibody Drugs to RNA Interference and Nanotherapy: The Evolution and Integration of Targeted Strategies in Gastric Cancer.International journal of nanomedicine · 2026Review
- METTL10-Mediated PIAS3 Methylation Links Purine Metabolism to Gastric Cancer Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Decoding the functional roles of circular RNAs linked to NF-κB pathway in carcinogenesis.Discover oncology · 2025Review
- Anoikis resistance in Cancer: Mechanisms, therapeutic strategies, potential targets, and models for enhanced understanding.Cancer letters · 2025Review
- PRMT1-catalyzed NUSAP1 methylation enhances Notch2 signaling and 5-FU resistance in gastric cancer.Cell death & disease · 2025Article
- Ubiquitination regulation of mitochondrial homeostasis: a new sight for the treatment of gastrointestinal tumors.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Chemoresistance poses a significant clinical challenge in the treatment of gastric cancer (GC), while its underlying molecular mechanisms are still not fully understood. Post-translational protein modification and abnormal activation of nuclear factor-kappa B (NF-κB) are critical regulators of tumor chemoresistance. This study investigates the role of TNF receptors-associated factors 6 (TRAF6) in 5-Fluorouracil (5-FU) resistant GC. Utilizing short hairpin RNA (shRNA) to suppress TRAF6 expression in 5-FU resistant GC cells across both in vivo and in vitro models, we observed a marked reduction in cell proliferation and tumor growth. Low expression of TRAF6 inhibited nuclear translocation of NF-κB-p65, which was achieved by promoting the expression of Interferon regulatory factor 3 (IRF3). Importantly, TRAF6, an E3 ubiquitin ligase, bound to the IRF3-Δ (SR + IAD) (1-190aa) domain, inducing Lys70 ubiquitination of IRF3 to regulate its protein stability, with ubiquitin K48 residue playing a crucial role in this process. In conclusion, our study reveals the mechanism by which the TRAF6/IRF3 axis decreases GC's cells sensitivity to 5-FU by promoting nuclear translocation of NF-κB-p65, offering valuable insights into overcoming chemoresistance in GC.
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