铜是一种微量元素和重要的辅助因子，在维持生物功能中起着至关重要的作用。最近的证据表明铜水平、癌症发展和转移之间存在显着相关性。铜的强氧化还原活性特性对癌细胞既有好处也有坏处。主要负责铜的吸收和调节的肠道可能会遭受铜稳态失衡的影响。结直肠癌（CRC）是最常见的原发性肠道癌症，是一种侵袭性恶性疾病，治疗选择有限。目前的研究主要集中在铜和CRC之间的关系。人们正在探索诸如铜形成和铜凋亡等创新概念，以了解与铜相关的细胞增殖和死亡。铜质形成是由酶促和非酶促铜调节活性介导的细胞增殖调节。而铜凋亡是指过量铜通过促进三羧酸循环内硫酰化蛋白的异常寡聚以及降低铁硫簇蛋白的水平而诱导的细胞死亡。对铜相关细胞增殖和死亡机制的全面了解为结直肠癌的治疗提供了新途径。在这篇综述中，我们总结了不断演变的分子机制，从异常的细胞内铜浓度到正在发现的铜相关蛋白，并讨论了铜在结直肠癌发病机制、进展和潜在疗法中的作用。了解铜与 CRC 之间的关系将有助于为 CRC 管理中的创新治疗策略提供全面的理论基础。© 2024 作者。约翰·威利出版的《临床与转化医学》

Copper, a trace element and vital cofactor, plays a crucial role in the maintenance of biological functions. Recent evidence has established significant correlations between copper levels, cancer development and metastasis. The strong redox-active properties of copper offer both benefits and disadvantages to cancer cells. The intestinal tract, which is primarily responsible for copper uptake and regulation, may suffer from an imbalance in copper homeostasis. Colorectal cancer (CRC) is the most prevalent primary cancer of the intestinal tract and is an aggressive malignant disease with limited therapeutic options. Current research is primarily focused on the relationship between copper and CRC. Innovative concepts, such as cuproplasia and cuproptosis, are being explored to understand copper-related cellular proliferation and death. Cuproplasia is the regulation of cell proliferation that is mediated by both enzymatic and nonenzymatic copper-modulated activities. Whereas, cuproptosis refers to cell death induced by excess copper via promoting the abnormal oligomerisation of lipoylated proteins within the tricarboxylic acid cycle, as well as by diminishing the levels of iron-sulphur cluster proteins. A comprehensive understanding of copper-related cellular proliferation and death mechanisms offers new avenues for CRC treatment. In this review, we summarise the evolving molecular mechanisms, ranging from abnormal intracellular copper concentrations to the copper-related proteins that are being discovered, and discuss the role of copper in the pathogenesis, progression and potential therapies for CRC. Understanding the relationship between copper and CRC will help provide a comprehensive theoretical foundation for innovative treatment strategies in CRC management.© 2024 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.