Emerging Roles of the Copper-CTR1 Axis in Tumorigenesis

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.