Slc39a1, also known as ZIP1, is a zinc ion transport protein. It is involved in zinc homeostasis and is associated with various biological processes. It has been linked to pathways like the cell cycle, Wnt signaling pathway, and is crucial for processes such as cell proliferation, invasion, and migration. Genetic models, especially knockout (KO) mouse models, can help in understanding its functions [1,2,3,4,5,6].

Triple-knockout mice lacking Slc39a1-3 genes showed no overt phenotypic effect when fed a zinc-adequate diet. However, when on a zinc-deficient diet, these mice had more severely reduced embryonic membrane-bound alkaline phosphatase activity, a higher proportion of abnormally developing embryos, and impaired accumulation/retention of zinc in the liver and pancreas compared to wild-type mice, indicating the importance of these genes, including Slc39a1, in adaptation to zinc deficiency [6]. In cancer research, knockdown of Slc39a1 in hepatocellular carcinoma (HCC) cells repressed their proliferation, invasion, and migration abilities, and decreased the expression of tumor-progression and Wnt-signaling-related proteins [1]. In glioma cells, knockdown experiments in vitro showed that Slc39a1 promotes cell proliferation, inhibits apoptosis, and affects the expression of MMP2/MMP9 [2]. In gastric cancer, overexpressing Slc39a1 promoted growth and invasion in vitro and in vivo, while silencing had opposite effects [3].

In conclusion, Slc39a1 is essential for zinc homeostasis, especially during zinc deficiency. In cancer, it plays a role in promoting the malignant progression of various tumors such as HCC, glioma, and gastric cancer. The study of Slc39a1 knockout mouse models has provided insights into its functions in zinc-related physiological processes and its role in cancer development, which may contribute to the discovery of new prognostic and therapeutic targets for cancer [1,2,3,6].