PhD School in Cellular and Molecular Biology, Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica 1, 00133 Rome, Italy.
Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica 1, 00133 Rome, Italy.
Life Sci. 2024 Oct 1;354:122972. doi: 10.1016/j.lfs.2024.122972. Epub 2024 Aug 13.
The complex process known as epithelial to mesenchymal transition (EMT) plays a fundamental role in several biological settings, encompassing embryonic development, wound healing, and pathological conditions such as cancer and fibrosis. In recent years, a bulk of research has brought to light the key role of copper, a trace element with essential functions in cellular metabolism, cancer initiation and progression. Indeed, copper, besides functioning as cofactor of enzymes required for essential cellular processes, such as energy production and oxidation reactions, has emerged as an allosteric regulator of kinases whose activity is required to fulfill cancer dissemination through the EMT. In this comprehensive review, we try to describe the intricate relationship between the transition metal copper and EMT, spanning from the earliest foundational studies to the latest advancements. Our aim is to shed light on the multifaceted roles undertaken by copper in EMT in cancer and to unveil the diverse mechanisms by which copper homeostasis exerts its influence over EMT regulators, signaling pathways, cell metabolic reprogramming and transcription factors ultimately contributing to the spread of cancer. Therefore, this review not only may contribute to a deeper comprehension of copper-mediated mechanisms in EMT but also supports the hypothesis that targeting copper may contribute to counteract the progression of EMT-associated pathologies.
上皮间质转化（EMT）是一个复杂的过程，在多种生物学环境中起着至关重要的作用，包括胚胎发育、创伤愈合以及癌症和纤维化等病理状况。近年来，大量研究揭示了铜的关键作用，铜是一种在细胞代谢、癌症发生和进展中具有重要功能的微量元素。事实上，铜除了作为必需细胞过程（如能量产生和氧化反应）所需酶的辅助因子外，还作为其活性对于通过 EMT 实现癌症扩散所必需的激酶的变构调节剂出现。在这篇全面的综述中，我们试图描述过渡金属铜与 EMT 之间的复杂关系，从最早的基础研究到最新的进展。我们的目的是阐明铜在癌症 EMT 中的多方面作用，并揭示铜稳态通过 EMT 调节剂、信号通路、细胞代谢重编程和转录因子发挥其影响的多种机制，最终促进癌症的扩散。因此，这篇综述不仅可以帮助我们更深入地理解 EMT 中铜介导的机制，还支持了这样一种假设，即靶向铜可能有助于对抗 EMT 相关病理的进展。
