PAK6通过影响DNA损伤修复促进乳腺癌细胞凋亡

doi:10.3870/j.issn.1672-8009.2026.01.002

摘要/Abstract

摘要： 目的解析P21激活激酶6(P21-activated kinase 6,PAK6)在乳腺癌中的表达、临床意义、潜在的生物学功能和初步的作用机制,并评估其作为乳腺癌预后标志物和治疗靶点的可行性。方法利用癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)的乳腺癌表达谱数据,分析PAK6的表达及其与患者预后的关系。基于转录组数据和单细胞转录组测序数据分析探索PAK6的潜在生物学功能。在人乳腺癌细胞系MCF7和MDA-MB-231中构建PAK6过表达和敲低模型,利用JC-1染色、细胞凋亡检测和蛋白质印迹法分析PAK6对细胞凋亡和DNA损伤应答的影响。结果 PAK6在乳腺癌组织中显著高表达,且其高表达与患者的总生存期、无进展生存期、疾病特异性生存期和无复发生存期呈负相关(P<0.05)。GSEA结果显示PAK6高表达组富集于DNA复制、细胞周期调控和DNA损伤修复等相关通路。单细胞分析发现PAK6主要在Malignant_C25、Malignant_C28和Malignant_C3恶性肿瘤细胞亚群中高表达,且Malignant_C25亚群富集了细胞周期和DNA复制相关通路,并可能具有向其他细胞类型转变的潜能。体外实验证实,PAK6过表达抑制乳腺癌细胞凋亡,并升高DNA损伤标志物γH2AX的表达水平;而PAK6敲低则促进细胞凋亡并下调γH2AX的表达水平。结论 PAK6在乳腺癌中高表达并与不良预后相关,其可能通过促进DNA复制、加速细胞周期进程、抑制细胞凋亡和调控DNA损伤应答发挥促癌作用。PAK6有望成为乳腺癌的潜在预后标志物和治疗靶点。

关键词: 乳腺癌, PAK6, DNA损伤应答, 单细胞测序

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

中图分类号:

R737.9

王曦, 陆礼. PAK6通过影响DNA损伤修复促进乳腺癌细胞凋亡[J]. 医学分子生物学杂志, 2026, 23(1): 9-18.

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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