SLC transporters as metalloptotic gatekeepers in tumorigenesis: From molecular mechanisms to clinical potential

Solute carrier (SLC) transporters exert a crucial effect on metalloptosis in tumors via governing the translocation of ions and amino acids across cellular and organelle membranes. Disruptions in metal ion homeostasis mediated by SLC transporters, along with the subsequent induction of metalloptosis, are pivotal factors in tumor initiation and progression. However, the precise biological roles and clinical implications of SLC transporters in cancer remain incompletely interpreted. This review systematically summarizes the structural and functional features of SLC transporters in mediating metalloptosis and underscores their significant roles in cancer biology. We further delineate the regulatory mechanisms of SLC transporters in metal ion flux and amino acid metabolism, emphasizing their dynamic interplay in modulating metalloptosis during tumorigenesis. Furthermore, we provide a detailed overview of the complex crosstalk among SLC transporters, metal ions, and metalloptosis pathways, and highlight the role of SLC transporters in cancer, paving novel avenues for innovative anticancer strategies.