Department of Gastroenterology, Second Xiangya Hospital, Central South University, Changsha 410011, China.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2023;48(9):1368-1376. doi: 10.11817/j.issn.1672-7347.2023.230083.
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.
铜与铁一样，是人体细胞必需的微量元素。铁过载和铁死亡在肿瘤中的作用已逐渐阐明，但铜过载和铜死亡的作用仍在探索中。铜死亡是一种新的细胞死亡方式，继发于铜过载引起的线粒体功能障碍，其特征是铜依赖性和程序性的。过量的铜通过与线粒体三羧酸 (TCA) 循环中的巯基蛋白结合，导致蛋白毒性应激，破坏细胞内稳态并引发铜死亡。铜积累对正常细胞具有致癌作用，对肿瘤细胞具有双重作用。肝癌是中国乃至全球最常见的恶性肿瘤之一，其中肝细胞癌 (HCC) 是最常见的组织学亚型。铜在 HCC 中表现出双重性，它既能促进 HCC 细胞的生长和侵袭，又能通过诱导铜死亡发挥抗癌作用。此外，铜死亡相关基因可以作为免疫治疗效果的评估和预后模型的构建。阐明铜死亡在肝癌中的作用有助于探索肝癌筛查、治疗和预后评估的新方法。
