The solute carrier family 11 transporters: a bridge between iron homeostasis and tumor biology.

Iron is an essential trace element in the human body, and its imbalance is closely linked to the initiation and progression of various malignancies. The solute carrier family 11 (SLC11) transporters, comprising SLC11A1 and SLC11A2, play pivotal roles in iron metabolism and cellular homeostasis, processes intricately linked to oncogenesis. SLC11A1, primarily expressed in macrophages, modulates immune responses and reshapes the tumor microenvironment, while SLC11A2, a ubiquitous iron transporter, regulates dietary iron absorption and ferroptosis, an iron-dependent form of programmed cell death. Dysregulation of these transporters is associated with tumor initiation, progression, metastasis, and therapy resistance. In this review, we provide an overview of the physiological functions of SLC11 transporters in iron metabolism and their pathological roles in cancer biology. Emerging evidence highlights their involvement in key oncogenic pathways, including p53, JAK/STAT, Wnt and HIF signaling. Pharmacological and genetic interventions targeting SLC11 transporters have shown the potential to disrupt tumor progression and enhance treatment efficacy. By exploring the intricate roles of SLC11A1 and SLC11A2 in cancer progression, this review offers insights into their potential as biomarkers and therapeutic targets, paving the way for innovative cancer treatment strategies.