铜死亡在肝癌中的研究进展

Research progress in cuproptosis in liver cancer

铜和铁是人体细胞必需的金属元素。铁过载与铁死亡在肿瘤中的研究已逐步深入,但铜过载与铜死亡在肿瘤中的相关作用仍处在探索阶段。铜死亡是一种铜依赖的、程序性的、新型的细胞死亡方式,继发于铜过载诱发的线粒体功能受损。过量的铜通过结合线粒体三羧酸(tricarboxylic acid,TCA)循环中的硫辛酰化蛋白,造成蛋白毒性应激反应,破坏细胞内稳态,诱发铜死亡。铜堆积对正常细胞有致癌作用,对肿瘤细胞具有双重作用。肝癌是中国乃至全球常见恶性肿瘤之一,组织学亚型以肝细胞癌最为多见。铜在肝癌中具有两面性,既参与肝肿瘤细胞的生长与侵袭,又通过诱发铜死亡发挥抗癌作用;铜死亡相关基因具有评估免疫治疗效果和构建预后模型的潜能。阐明铜死亡在肝癌中的作用有助于发掘新的肝癌筛查、治疗及预后评估手段。

Copper,like iron,is an essential trace metal element for human cells.The role of iron overload and ferroptosis has been gradually clarified in tumors,but the role of copper overload and cuproptosis is still being explored.Cuproptosis is a novel mode of cell death,secondary to impaired mitochondrial function induced by copper overload,and characterized by copper-dependent and programmed.The excessive copper leads to protein toxicity stress by binding to sulfhydryl proteins in the tricarboxylic acid(TCA)cycle of mitochondria,disrupting cellular homeostasis and triggering cuproptosis.Copper accumulation has carcinogenic effects on normal cells,dual effects on tumor cells.Liver cancer is one of the most common malignant tumors in China and even globally,with hepatocellular carcinoma(HCC)being the most common histological subtype.Copper exhibits dualism in HCC,as it both contributes to the growth and invasion of HCC cells,and exerts anticancer effects by inducing cuproptosis.Also,cuproptosis-related genes can be the evaluation of immunotherapy effect and the construction of prognostic models.Clarifying the role of copper death in liver cancer can help explore new methods for liver cancer screening,treatment,and prognosis evaluation.