ArticleCell death & disease2022
PAK6 promotes homologous-recombination to enhance chemoresistance to oxaliplatin through ATR/CHK1 signaling in gastric cancer.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 37 citations in OpenAlex.
- Artificial Intelligence in Gastric Cancer: Diagnostic, Prognostic, and Predictive Developments, Evidence Maturity, and Translational Challenges.Cancer reports (Hoboken, N.J.) · 2026Review
- Targeting KIF18B overcomes oxaliplatin resistance in esophageal squamous cell carcinoma via suppression of the ATR/CHK1 axis.Molecular genetics and genomics : MGG · 2026Article
- AZD6738 overcomes acquired olaparib resistance in BRCA1 mutation triple-negative breast cancer through down-regulation of BRCA2 and RAD51.Scientific reports · 2026Article
- Elevated NDRG1 Expression Drives Oxaliplatin Chemoresistance in Bladder Cancer Cells by Promoting Homologous Recombination Repair and Inhibiting GCell biochemistry and biophysics · 2026Article
- Metallic elements and their molecular roles in gastric cancer: Pathogenic mechanisms and therapeutic implications.World journal of gastrointestinal oncology · 2026Review
- NSMF modulates replication stress to facilitate colorectal cancer progression.Nucleic acids research · 2026Article
- Molecular Subtypes of Mixed Gastric Cancer Defined by Machine Learning for Predicting Prognosis and Treatment Response.Current medicinal chemistry · 2026Article
- Prognostic and Immunomodulatory Roles of PAK6 in Colorectal Cancer Through Integrative Transcriptomic and Clinical Analysis.Cancers · 2025Article
- ATR-CHK1 Axis Inhibitors in Gastric Cancer Treatment.International journal of molecular sciences · 2025Review
- Identification of a PAK6-Mediated MDM2/p21 Axis That Modulates Survival and Cell Cycle Control of Drug-Resistant Stem/Progenitor Cells in Chronic Myeloid Leukemia.International journal of molecular sciences · 2025Article
- The Role of the p21-Activated Kinase Family in Tumor Immunity.International journal of molecular sciences · 2025Review
- Multi-Pathway Study for Oxaliplatin Resistance Reduction.Current issues in molecular biology · 2025Review
- Uridine-cytidine kinase 2 is correlated with immune, DNA damage repair and promotion of cancer stemness in pan-cancer.Frontiers in oncology · 2025Article
- Article
- MD-Syn: synergistic drug combination prediction based on a multidimensional feature fusion method and attention mechanisms.Frontiers in pharmacology · 2025Article
- Transcriptomic response of overexpression ZNF32 in breast cancer cells.Scientific reports · 2024Article
- EZH1/2 plays critical roles in oocyte meiosis prophase I in mice.Biological research · 2024Article
- Ethanol extract of Vanilla planifolia stems reduces PAK6 expression and induces cell death in glioblastoma cells.Journal of cellular and molecular medicine · 2024Article
- Screening of gastric cancer diagnostic biomarkers in the homologous recombination signaling pathway and assessment of their clinical and radiomic correlations.Cancer medicine · 2024Article
- Urinary exosome proteins PAK6 and EGFR as noninvasive diagnostic biomarkers of diabetic nephropathy.BMC nephrology · 2023Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chemoresistance remains the primary challenge of clinical treatment of gastric cancer (GC), making the biomarkers of chemoresistance crucial for treatment decision. Our previous study has reported that p21-actived kinase 6 (PAK6) is a prognostic factor for selecting which patients with GC are resistant to 5-fluorouracil/oxaliplatin chemotherapy. However, the mechanistic role of PAK6 in chemosensitivity remains unknown. The present study identified PAK6 as an important modulator of the DNA damage response (DDR) and chemosensitivity in GC. Analysis of specimens from patients revealed significant associations between the expression of PAK6 and poorer stages, deeper invasion, more lymph node metastases, higher recurrence rates, and resistance to oxaliplatin. Cells exhibited chemosensitivity to oxaliplatin after knockdown of PAK6, but showed more resistant to oxaliplatin when overexpressing PAK6. Functionally, PAK6 mediates cancer chemoresistance by enhancing homologous recombination (HR) to facilitate the DNA double-strand break repair. Mechanistically, PAK6 moves into nucleus to promote the activation of ATR, thereby further activating downstream repair protein CHK1 and recruiting RAD51 from cytoplasm to the DNA damaged site to repair the broken DNA in GC. Activation of ATR is the necessary step for PAK6 mediated HR repair to protect GC cells from oxaliplatin-induced apoptosis, and ATR inhibitor (AZD6738) could block the PAK6-mediated HR repair, thereby reversing the resistance to oxaliplatin and even promoting the sensitivity to oxaliplatin regardless of high expression of PAK6. In conclusion, these findings indicate a novel regulatory mechanism of PAK6 in modulating the DDR and chemoresistance in GC and provide a reversal suggestion in clinical decision.
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