中国癌症杂志2025，Vol.35Issue(12)：1148-1153,6.DOI:10.19401/j.cnki.1007-3639.2025.12.007
着丝粒蛋白A驱动的染色体不稳定性与乳腺癌相关性研究的进展及展望:机制、预后及临床靶向治疗应用
Progress and prospects of CENPA-driven chromosomal instability in breast cancer:mechanisms,prognostic implications,and therapeutic perspectives
摘要
Abstract
Centromere protein A(CENPA),a specific variant of histone H3,plays a crucial role in maintaining the structure of centromeric chromatin and ensuring accurate chromosome segregation.Recent studies have shown that CENPA is highly expressed in various solid tumors,with particularly prominent upregulation in breast cancer.This aberrant elevation is closely associated with increased tumor aggressiveness and contributes to chromosomal instability and alterations in epigenetic regulatory networks,thereby promoting tumor initiation and progression.Based on a systematic review of the expression patterns,molecular mechanisms,prognostic relevance,and therapeutic research on CENPA in breast cancer,this paper summarized recent advances in four main areas:regarding expression profiles,CENPA is markedly elevated in different molecular subtypes,especially in estrogen receptor(ER)-negative and triple-negative breast cancers;in mechanistic studies,several key regulatory pathways have been identified,including pRb loss,the MBNL1-AS1/ZFP36 axis,FOXM1 with m6A modification,and the downstream PLA2R1/HHEX pathway;in clinical significance,CENPA and its chaperone HJURP have been recognized as prognostic indicators and are linked to endocrine and chemotherapy responses;in therapeutic exploration,potential strategies such as Plk1 inhibitors,anti-CENPA monoclonal antibodies,and RNA interference have been proposed.By integrating current findings,this review discussed the opportunities and challenges of targeting CENPA in precision therapy for breast cancer,providing a reference for developing individualized treatment approaches.关键词
着丝粒蛋白A/乳腺癌/染色体不稳定性/预后标志物/信号转导通路/靶向治疗Key words
CENPA/Breast cancer/Chromosomal instability/Prognostic biomarker/Signaling pathways/Targeted therapy分类
医药卫生引用本文复制引用
LU Ye,ZHANG Wenxiang,KONG Xiangyi,FANG Yi,WANG Jing,GAO Jidong..着丝粒蛋白A驱动的染色体不稳定性与乳腺癌相关性研究的进展及展望:机制、预后及临床靶向治疗应用[J].中国癌症杂志,2025,35(12):1148-1153,6.基金项目
国 家 自 然 科 学 基 金(82303464) （82303464）
中央高水平医院临床科研业务费及中国医学科学院肿瘤医院-深圳医院合作基金(CFA202202017). National Natural Science Foundation of China(82303464) （CFA202202017）
National High Level Hospital Clinical Research Funding and Cooperation Fund of CHCAMS and SZCH(CFA202202017). （CFA202202017）
