中国普通外科杂志2024,Vol.33Issue(7):1172-1179,8.DOI:10.7659/j.issn.1005-6947.2024.07.016
铜死亡在肝细胞癌发病机制中的研究进展
Cuproptosis in the pathogenesis of hepatocellular carcinoma:a research progress review
摘要
Abstract
Copper is one of the essential trace elements for living organisms.Both copper deficiency and overload can damage cells,and maintaining intracellular copper levels within a reasonable range is crucial.Cuproptosis is a newly established distinct form of programmed cell death.It is primarily characterized by mitochondrial dysfunction.Copper overload in cells can lead to abnormal oligomerization of acylated proteins in the tricarboxylic acid cycle and loss of Fe-S cluster proteins,causing proteotoxic stress responses that disrupt intracellular homeostasis,triggering cuproptosis.One of the conditions for cuproptosis is the higher concentration of copper in hepatocellular carcinoma(HCC)cells compared to normal cells.Cuproptosis plays a crucial role in the development and progression of HCC,contributing significantly to angiogenesis promotion,immune evasion,regulation of classical signaling pathways,and induction of other cell death modalities.Cuproptosis impacts cellular homeostasis and participates in regulating various biological processes.In the immune microenvironment of HCC,bioinformatics analysis has revealed a correlation between cuproptosis and the infiltration of immune cells such as CD8+T cells,follicular dendritic cells,and helper T cells.Its molecular regulatory mechanisms hold the potential to overcome drug resistance,including resistance to anti-PD-L1 therapy and sorafenib.Copper ion carriers like disulfiram can activate other cell death programs,enhancing the sensitivity of HCC treatment and overcoming drug resistance.The anti-tumor strategy of combining copper nanoparticles with copper ion carriers shows promising prospects.Establishing HCC prognostic models based on cuproptosis-related genes offers advantages,but further mechanistic studies and clinical validation are required.In summary,this paper reviews and discusses the key advances and focal points of cuproptosis in the pathogenesis of HCC,aiming to provide a reference for related research.关键词
癌,肝细胞/铜死亡/肿瘤微环境/综述Key words
Carcinoma,Hepatocellular/Cuproptosis/Tumor Microenvironment/Review分类
医药卫生引用本文复制引用
董昌君,张先林..铜死亡在肝细胞癌发病机制中的研究进展[J].中国普通外科杂志,2024,33(7):1172-1179,8.基金项目
湖北省自然科学基金资助项目(2022CFB328). (2022CFB328)