PAK6 Promotes Apoptosis of Breast Cancer Cells by Affecting DNA Damage Repair

doi:10.3870/j.issn.1672-8009.2026.01.002

Abstract

Abstract: Objective To comprehensively analyze the expression,clinical significance,potential biological functions,and preliminary mechanisms of PAK6 in breast cancer,and to evaluate its feasibility as a prognostic biomarker and therapeutic target for breast cancer. Methods Breast cancer expression profile data from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)were utilized to analyze the expression of PAK6 and its relationship with patient prognosis.Potential biological functions of PAK6 were explored based on transcriptome data and single-cell RNA sequencing data.The overexpression and knockdown models of PAK6 were established in human breast cancer cell lines MCF7 and MDA-MB-231.JC-1 staining,apoptosis detection,and Western blotting were used to analyze the effects of PAK6 on cell apoptosis and DNA damage response. Results PAK6 was significantly overexpressed in breast cancer tissues,and its high expression was negatively correlated with overall survival,progression-free survival,disease-specific survival,and relapse-free survival in patients(P<0.05).GSEA results showed that the PAK6 high-expression group was enriched in pathways related to DNA replication,cell cycle regulation,and DNA damage repair.Single-cell analysis revealed that PAK6 was predominantly highly expressed in Malignant_C25,Malignant_C28,and Malignant_C3 malignant tumor cell subpopulations.Notably,the Malignant_C25 subpopulation showed enrichment for cell cycle and DNA replication-related pathways and exhibited the potential to transition to other cell types.In vitro experiments confirmed that PAK6 overexpression inhibited apoptosis and decreased the phosphorylation level of the DNA damage marker γH2AX in breast cancer cells,whereas PAK6 knockdown promoted apoptosis and increased γH2AX phosphorylation. Conclusion PAK6 is overexpressed in breast cancer and is associated with poor prognosis.It may play a pro-oncogenic role by promoting DNA replication,accelerating cell cycle progression,inhibiting apoptosis,and regulating DNA damage response.PAK6 shows promise as a potential prognostic biomarker and therapeutic target for breast cancer.

Key words: breast cancer, P21-activated kinase 6, DNA damage response, single-cell sequencing

CLC Number:

R737.9

WANG Xi, LU Li. PAK6 Promotes Apoptosis of Breast Cancer Cells by Affecting DNA Damage Repair[J]. Journal of Medical Molecular Biology, 2026, 23(1): 9-18.

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