ZIP6-centered zinc regulatory and malignant characteristics of breast cancer cells

Abstract

Zinc (Zn) is an essential trace element for numerous biological events in mammals. Zn functions as a signaling mediator, leading to the regulation of physiological cell actions and, therefore, has therapeutic potential. Recent breast cancer research has shown that Zn transporters contribute to malignancy processes; thus, elucidating the roles of Zn and Zn transporters in breast cancer may lead to the development of novel strategies for breast cancer diagnosis and therapy. The Zn transporter ZIP6 mediates the acquisition of malignant phenotypes such as hypoxic resistance and epithelial-mesenchymal transition (EMT), which determine breast tumor grade and prognosis. ZIP6 expression contributes to the efficacy of anticancer therapy through Zn-induced autophagy. The maintenance of breast cancer stem-like cells requires Zn modulation through the cooperative function of ZIP6 and ZIP7. These findings suggest that the ZIP6-mediated Zn network is a potent driving force toward malignancy. In this review, we summarize recent progress in understanding the emerging roles of Zn and ZIP6 in the regulation of malignant characteristics related to hypoxic adaptive response, drug therapy, and stemness. We also discuss the possibility and future challenges of innovative breast cancer therapies using ZIP6 and Zn-related molecules.

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