ArticleCell death & disease2014
JWA reverses cisplatin resistance via the CK2-XRCC1 pathway in human gastric cancer cells.
Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 58 citations in OpenAlex.
- Autophagy as a therapeutic target for cisplatin-resistant gastric cancer.Genes & diseases · 2026Review
- Lnc00892 enhances cisplatin sensitivity by inducing apoptosis through the BTAF1/MDM2/STAT5B/XIAP axis in bladder cancer cells.Biology direct · 2026Article
- ARL6IP5 in cancers: bidirectional function and therapeutic value.Cancer gene therapy · 2025Review
- Comparison of CX-4945 and SGC-CK2-1 as inhibitors of CSNK2 using quantitative phosphoproteomics: Triple SILAC in combination with inhibitor-resistant CSNK2.Current research in chemical biology · 2023Article
- Review
- JAC4 Protects from X-ray Radiation-Induced Intestinal Injury by JWA-Mediated Anti-Oxidation/Inflammation Signaling.Antioxidants (Basel, Switzerland) · 2022Article
- Glucose Increases STAT3 Activation, Promoting Sustained XRCC1 Expression and Increasing DNA Repair.International journal of molecular sciences · 2022Article
- ARL6IP5 reduces cisplatin-resistance by suppressing DNA repair and promoting apoptosis pathways in ovarian carcinoma.Cell death & disease · 2022Article
- Chemical Genetic Validation of CSNK2 Substrates Using an Inhibitor-Resistant Mutant in Combination with Triple SILAC Quantitative Phosphoproteomics.Frontiers in molecular biosciences · 2022Article
- JWA suppresses proliferation in trastuzumab-resistant breast cancer by downregulating CDK12.Cell death discovery · 2021Article
- Exosomal microRNA-588 from M2 polarized macrophages contributes to cisplatin resistance of gastric cancer cells.World journal of gastroenterology · 2021Article
- Activated STAT3 Is a Novel Regulator of theInternational journal of molecular sciences · 2021Article
- CX-4945 and siRNA-Mediated Knockdown of CK2 Improves Cisplatin Response in HPV(+) and HPV(-) HNSCC Cell Lines.Biomedicines · 2021Article
- ALKBH5 Inhibited Cell Proliferation and Sensitized Bladder Cancer Cells to Cisplatin by m6A-CK2α-Mediated Glycolysis.Molecular therapy. Nucleic acids · 2021Article
- Application of gene polymorphisms to predict the sensitivity of patients with locally advanced non-small cell lung cancer undergoing chemoradiotherapy.American journal of translational research · 2021Article
- miR-338-5p-ZEB2 axis in Diagnostic, Therapeutic Predictive and Prognostic Value of Gastric Cancer.Journal of Cancer · 2021Article
- JP3 enhances the toxicity of cisplatin on drug-resistant gastric cancer cells while reducing the damage to normal cells.Journal of Cancer · 2021Article
- The long noncoding RNA CRAL reverses cisplatin resistance via the miR-505/CYLD/AKT axis in human gastric cancer cells.RNA biology · 2020Review
- PD-L1 monoclonal antibody-decorated nanoliposomes loaded with Paclitaxel and P-gp transport inhibitor for the synergistic chemotherapy against multidrug resistant gastric cancers.Nanoscale research letters · 2020Article
- Silencing of circRACGAP1 sensitizes gastric cancer cells to apatinib via modulating autophagy by targeting miR-3657 and ATG7.Cell death & disease · 2020Article
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Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gastric cancer is the third most common malignancy in China, with a median 5-year survival of only 20%. Cisplatin has been used in first-line cancer treatment for several types of cancer including gastric cancer. However, patients are often primary resistant or develop acquired resistance resulting in relapse of the cancer and reduced survival. Recently, we demonstrated that the reduced expression of base excision repair protein XRCC1 and its upstream regulator JWA in gastric cancerous tissues correlated with a significant survival benefit of adjuvant first-line platinum-based chemotherapy as well as XRCC1 playing an important role in the DNA repair of cisplatin-resistant gastric cancer cells. In the present study, we demonstrated the role of JWA in cisplatin-induced DNA lesions and aquired cisplatin resistance in five cell-culture models: gastric epithelial cells GES-1, cisplatin-sensitive gastric cancer cell lines BGC823 and SGC7901, and the cisplatin-resistant gastric cancer cell lines BGC823/DDP and SGC7901/DDP. Our results indicated that JWA is required for DNA repair following cisplatin-induced double-strand breaks (DSBs) via XRCC1 in normal gastric epithelial cells. However, in gastric cancer cells, JWA enhanced cisplatin-induced cell death through regulation of DNA damage-induced apoptosis. The protein expression of JWA was significantly decreased in cisplatin-resistant cells and contributed to cisplatin resistance. Interestingly, as JWA upregulated XRCC1 expression in normal cells, JWA downregulated XRCC1 expression through promoting the degradation of XRCC1 in cisplatin-resistant gastric cancer cells. Furthermore, the negative regulation of JWA to XRCC1 was blocked due to the mutation of 518S/519T/523T residues of XRCC1, and indicating that the CK2 activated 518S/519T/523T phosphorylation is a key point in the regulation of JWA to XRCC1. In conclusion, we report for the first time that JWA regulated cisplatin-induced DNA damage and apoptosis through the CK2-P-XRCC1-XRCC1 pathway, indicating a putative drug target for reversing cisplatin resistance in gastric cancer.
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