Department of Liver Surgery, Hepatobiliary Pancreatic Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Institute of Precision Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Mol Cancer Res. 2022 Sep 2;20(9):1339-1353. doi: 10.1158/1541-7786.MCR-22-0056.
Physiologic roles of copper in metabolic homeostasis have been well established; however, whether and how copper is dysregulated in tumors and contributes to tumorigenesis is not recapitulated. Here, we comprehensively summarize the potential origins of copper accumulation in diseases, especially in cancers, by dysregulating copper transporter 1 (CTR1) or ATPase copper transporting alpha/beta (ATP7A/B) and further demonstrate the underlying mechanism of copper contributing to tumorigenesis. Specifically, in addition to modulating reactive oxygen species (ROS), angiogenesis, immune response, and metabolic homeostasis, copper recently has drawn more attention by directly binding to oncoproteins such as MEK, ULK, Memo, and PDK1 to activate distinct oncogenic signals and account for tumorigenesis. In the end, we disclose the emerging applications of copper in cancer diagnosis and highlight the promising strategies to target the copper-CTR1 axis for cancer therapies.
铜在代谢稳态中的生理作用已得到充分证实；然而，铜在肿瘤中的失调情况及其对肿瘤发生的作用尚不清楚。在这里，我们通过调控铜转运蛋白 1 (CTR1) 或 ATP 酶铜转运 α/β (ATP7A/B) ，全面总结了铜在疾病中积累的潜在来源，特别是在癌症中，并进一步阐明了铜促进肿瘤发生的潜在机制。具体而言，除了调节活性氧 (ROS)、血管生成、免疫反应和代谢稳态外，铜最近通过直接与 MEK、ULK、Memo 和 PDK1 等癌蛋白结合，激活不同的致癌信号，从而引起更多关注，并解释了肿瘤发生的原因。最后，我们揭示了铜在癌症诊断中的新应用，并强调了针对铜-CTR1 轴的有前途的癌症治疗策略。
