Slc39a1, also known as ZIP1, is a zinc ion transport protein belonging to the zinc-iron permease family [3,6]. It is located on the cell membrane and functions as a zinc uptake transporter. It is involved in various biological processes, such as being part of a specialized metabolic pathway in osteoblasts that regulates citrate uptake, production, and deposition into bone, through its coordinated function with the citrate transporter SLC13A5 [7].

In multiple cancers, Slc39a1 shows diverse roles. In hepatocellular carcinoma, its overexpression promotes malignant progression, is associated with worse prognosis, and may lead to immunosuppression by increasing Th2 cell infiltration and reducing cytotoxic cell infiltration [1]. In gliomas, high expression of Slc39a1 predicts poor survival, promotes cell proliferation, inhibits apoptosis, and may affect immune cell infiltration into the microenvironment [2]. In gastric adenocarcinoma, high expression promotes cancer cell growth and invasion, and is an independent unfavorable prognostic factor [4]. In renal cell carcinoma, transfection of Slc39a1 impairs tumor metabolism and perturbs metabolism-related pathways [5]. In early-stage hepatocellular carcinoma, decreased Slc39a1 expression is associated with a poorer prognosis [3].

In conclusion, Slc39a1 is crucial in zinc transport and is involved in various biological and disease-related processes, especially in cancer. Studies on Slc39a1 in different disease models, especially in cancer, help us understand its role in disease development, which may provide potential prognostic and therapeutic targets.

References:

1. Ma, Xiaowu, Zhuang, Hongkai, Wang, Qingbin, Chen, Yajin, Shang, Changzhen. 2022. SLC39A1 Overexpression is Associated with Immune Infiltration in Hepatocellular Carcinoma and Promotes Its Malignant Progression. In Journal of hepatocellular carcinoma, 9, 83-98. doi:10.2147/JHC.S349966. https://pubmed.ncbi.nlm.nih.gov/35211427/

2. Wang, Peng, Zhang, Jingjing, He, Shuai, Xiao, Boan, Peng, Xiaobin. 2020. SLC39A1 contribute to malignant progression and have clinical prognostic impact in gliomas. In Cancer cell international, 20, 573. doi:10.1186/s12935-020-01675-0. https://pubmed.ncbi.nlm.nih.gov/33292262/

3. Zhang, Qinglin, Pan, Jiadong, An, Fangmei, Nie, He, Zhan, Qiang. . Decreased SLC39A1 (Solute carrier family 39 member 1) expression predicts unfavorable prognosis in patients with early-stage hepatocellular carcinoma. In Bioengineered, 12, 8147-8156. doi:10.1080/21655979.2021.1987131. https://pubmed.ncbi.nlm.nih.gov/34615436/

4. Yu, Dan, Chen, Yong, Luo, Ming, Peng, Yanjin, Yi, Shengen. 2022. Upregulated Solute Carrier SLC39A1 Promotes Gastric Cancer Proliferation and Indicates Unfavorable Prognosis. In Genetics research, 2022, 1256021. doi:10.1155/2022/1256021. https://pubmed.ncbi.nlm.nih.gov/36407082/

5. Yuan, Yulin, Liu, Zimeng, Li, Bohan, Zhang, Zhe, Dong, Xiao. 2022. Integrated analysis of transcriptomics, proteomics and metabolomics data reveals the role of SLC39A1 in renal cell carcinoma. In Frontiers in cell and developmental biology, 10, 977960. doi:10.3389/fcell.2022.977960. https://pubmed.ncbi.nlm.nih.gov/36407113/

6. Kambe, Taiho, Geiser, Jim, Lahner, Brett, Salt, David E, Andrews, Glen K. 2008. Slc39a1 to 3 (subfamily II) Zip genes in mice have unique cell-specific functions during adaptation to zinc deficiency. In American journal of physiology. Regulatory, integrative and comparative physiology, 294, R1474-81. doi:10.1152/ajpregu.00130.2008. https://pubmed.ncbi.nlm.nih.gov/18353881/

7. Dirckx, Naomi, Zhang, Qian, Chu, Emily Y, Schmidt-Rohr, Klaus, Clemens, Thomas L. 2022. A specialized metabolic pathway partitions citrate in hydroxyapatite to impact mineralization of bones and teeth. In Proceedings of the National Academy of Sciences of the United States of America, 119, e2212178119. doi:10.1073/pnas.2212178119. https://pubmed.ncbi.nlm.nih.gov/36322718/