ArticleJournal of advanced research2024
CDK2-activated TRIM32 phosphorylation and nuclear translocation promotes radioresistance in triple-negative breast cancer.
Article in Journal of advanced research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Meta-analysis of cellular phosphoproteome datasets exploring phospho-signaling associated with the RNA-binding protein RAVER1.Scientific reports · 2026Pooled it
- TRIM32-mediated ubiquitination of STING promotes glycolysis and tumor progression.Cell death and differentiation · 2026Article
- TRIM Protein Superfamily in Breast Cancer: Yin and Yang.Biochemical genetics · 2026Review
- TRIM32 drives head and neck squamous cell carcinoma progression via TP53 suppression and lysosomal/autophagy dysregulation.Translational cancer research · 2026Article
- Pin1 targets phosphorylated NCOA4 for K29/K48-linked ubiquitination to suppress ferritinophagy and ferroptosis in anaplastic thyroid cancer.Cell death & disease · 2026Article
- Article
- Nuclear-Cytoplasmic Axis in Cancer: From Protein Mislocalization to Anticancer Drug Resistance.Oncology research · 2026Review
- Activation of sphingosine-1-phosphate receptor 2 (S1PR2) upregulates dihydropyrimidine dehydrogenase (DPD) expression in colon cancer cells.Journal of advanced research · 2025Article
- Clinical features, treatment and prognosis analysis of distant metastatic esophageal cancer.Scientific reports · 2025Article
- The role and therapeutic value of NUSAP1 in human cancers.Journal of translational medicine · 2025Review
- Urea cycle dysregulation: a new frontier in cancer metabolism and immune evasion.Cell communication and signaling : CCS · 2025Review
- Identification of RASL11A as a gene conferring radiosensitivity in glioblastoma.Journal of neuro-oncology · 2025Article
- FAM50A as a novel prognostic marker modulates the proliferation of colorectal cancer cells via CylinA2/CDK2 pathway.PloS one · 2025Article
- Curcumin inhibits colorectal cancer progression by targeting PTBP1 and CDK2-mediated pathways.Frontiers in oncology · 2025Article
- Discovery of a DNA repair-associated radiosensitivity index for predicting radiotherapy efficacy in breast cancer.Frontiers in oncology · 2025Article
- Pentosan polysulfate alleviates interstitial cystitis/bladder pain syndrome by modulating bile acid metabolism and activating the TGR5 receptor through gut microbiota regulation.Bladder (San Francisco, Calif.) · 2025Article
- Targeting CDK2 to combat drug resistance in cancer therapy.Future oncology (London, England) · 2024Review
- Sanguinarine identified as a natural dual inhibitor of AURKA and CDK2 through network pharmacology and bioinformatics approaches.Scientific reports · 2024Article
- Emerging roles of tripartite motif family proteins (TRIMs) in breast cancer.Cancer medicine · 2024Review
- Pin1-catalyzed conformational regulation after phosphorylation: A distinct checkpoint in cell signaling and drug discovery.Science signaling · 2024Review
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Authors and funding
17 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionDespite radiotherapy being one of the major treatments for triple-negative breast cancer (TNBC), new molecular targets for its treatment are still required due to radioresistance. CDK2 plays a critical role in TNBC. However, the mechanism by which CDK2 promotes TNBC radioresistance remains to be clearly elucidated.
objectivesWe aimed to elucidate the relationship between CDK2 and TRIM32 and the regulation mechanism in TNBC.
methodsWe performed immunohistochemical staining to detect nuclear TRIM32, CDK2 and STAT3 on TNBC tissues. Western blot assays and PCR were used to detect the protein and mRNA level changes. CRISPR/Cas9 used to knock out CDK2. shRNA-knockdown and transfection assays also used to knock out target genes. GST pull-down analysis, immunoprecipitation (IP) assay and in vitro isomerization analysis also used. Tumorigenesis studies also used to verify the results in vitro.
resultsHerein, tripartite motif-containing protein 32 (TRIM32) is revealed as a substrate of CDK2. Radiotherapy promotes the binding of CDK2 and TRIM32, thus leading to increased CDK2-dependent phosphorylation of TRIM32 at serines 328 and 339. This causes the recruitment of PIN1, involved in cis-trans isomerization of TRIM32, resulting in importin α3 binding to TRIM32 and contributing to its nuclear translocation. Nuclear TRIM32 inhibits TC45-dephosphorylated STAT3, Leading to increased transcription of STAT3 and radioresistance in TNBC. These results were validated by clinical prognosis confirmed by the correlative expressions of the critical components of the CDK2/TRIM32/STAT3 signaling pathway.
conclusionsOur findings demonstrate that regulating the CDK2/TRIM32/STAT3 pathway is a promising strategy for reducing radioresistance in TNBC.
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