Slc39a6, also known as ZIP6 or LIV-1, is a zinc-transporter protein belonging to the solute carrier (SLC)39A family. It plays a crucial role in zinc homeostasis, transferring zinc to the cytoplasm when cells are zinc-depleted. Zinc is essential for various biological processes, and thus Slc39a6 is likely involved in multiple pathways related to cell function, growth, and development. Genetic models, such as gene-knockout models, can be valuable for studying its function.

In liver cancer, knockdown of Slc39a6 in HepG2 and Hep3B cells inhibited the proliferation, migration, and invasion of liver cancer cells both in vitro and in vivo, suggesting it may be a prognostic biomarker and is associated with liver cancer progression [1]. In zebrafish, the loss-of-function of zip6 (the zebrafish ortholog of Slc39a6) led to significant T lymphocyte reduction, decreased intracellular Zn levels, and increased caspase-related cell apoptosis, indicating its importance in T-cell development [2]. In esophageal squamous cell carcinoma (ESCC), suppression of Slc39a6 expression promoted cell apoptosis, abrogated proliferation and invasion, and induced an epithelial-to-mesenchymal transition (EMT) phenotype [3]. In gastric adenocarcinoma cell lines, knockdown of Slc39a6 inhibited cell proliferation, migration, and invasion [4].

In conclusion, Slc39a6 is essential for zinc homeostasis and T-cell development. Its role in cancer, including liver, esophageal, and gastric cancer, has been revealed through loss-of-function experiments. These findings suggest that Slc39a6 may be a potential target for cancer diagnosis, prognosis, and therapy. Understanding the function of Slc39a6 in these disease conditions through model-based research provides insights into disease mechanisms and possible treatment strategies.