Medical Research Center, The First Affiliated Hospital of Ningbo University, Ningbo, PR China; Department of Pathology, Health Science Center, Ningbo University, Ningbo, Ningbo, PR China.
Medical Research Center, The First Affiliated Hospital of Ningbo University, Ningbo, PR China.
Cancer Lett. 2023 May 1;561:216157. doi: 10.1016/j.canlet.2023.216157. Epub 2023 Apr 1.
Recent studies have established a strong link between copper and cancer biology, as copper is necessary for cancer growth and metastasis. Beyond the conventional concept of copper serving as a catalytic cofactor of metalloenzymes, emerging evidence demonstrates copper as a regulator for signaling transduction and gene expression, which are vital for tumorigenesis and cancer progression. Interestingly, strong redox-active properties make copper both beneficial and detrimental to cancer cells. Cuproplasia is copper-dependent cell growth and proliferation, whereas cuproptosis is copper-dependent cell death. Both mechanisms act in cancer cells, suggesting that copper depletion and copper supplementation may be viable approaches for developing novel anticancer therapies. In this review, we summarized the current understanding of copper's biological role and related molecular mechanisms in cancer proliferation, angiogenesis, metastasis, autophagy, immunosuppressive microenvironment development, and copper-mediated cancer cell death. We also highlighted copper-based strategies for cancer treatment. The current challenges of copper in cancer biology and therapy and their potential solutions were also discussed. Further investigation in this field will yield a more comprehensive molecular explanation for the causal relationship between copper and cancers. It will reveal a series of key regulators governing copper-dependent signaling pathways, thereby providing potential targets for developing copper-related anticancer drugs.
最近的研究已经确立了铜与癌症生物学之间的紧密联系，因为铜是癌症生长和转移所必需的。除了传统观念认为铜是金属酶的催化辅助因子之外，新出现的证据表明铜是信号转导和基因表达的调节剂，这对肿瘤发生和癌症进展至关重要。有趣的是，强大的氧化还原活性使铜对癌细胞既有益又有害。铜依赖性细胞生长和增殖是杯状增生，而铜依赖性细胞死亡是铜依赖性细胞死亡。这两种机制都在癌细胞中起作用，这表明铜耗竭和铜补充可能是开发新型抗癌疗法的可行方法。在这篇综述中，我们总结了目前对铜在癌症增殖、血管生成、转移、自噬、免疫抑制微环境发展以及铜介导的癌细胞死亡中的生物学作用及其相关分子机制的理解。我们还强调了基于铜的癌症治疗策略。还讨论了铜在癌症生物学和治疗中的当前挑战及其潜在解决方案。进一步研究这一领域将为铜与癌症之间的因果关系提供更全面的分子解释。它将揭示一系列控制铜依赖性信号通路的关键调节剂，从而为开发与铜相关的抗癌药物提供潜在目标。
