The following is a summary of “Ligand-independent signaling and migration of breast cancer cells expressing membrane androgen receptor, ZIP9 (SLC39A9),” published in the December 2023  issue of Endocrinology by Thomas, et al.

The transporter of zinc Furthermore, ZIP9 is a membrane androgen receptor responsible for mediating androgen-dependent zinc and G-protein signaling in cancer cells. It was done to modify tumorigenic responses. The potential for unliganded ZIP9 to elicit comparable reactions needs to be better understood. It suggested that these tumorigenic responses are zinc-dependent. ZIP9 overexpression in MDA-MB-231 breast cancer cells (ZIP9 cells) led to a rise in zinc levels, cell migration, and invasion. 

The phenomenon was duplicated using a zinc ionophore and inhibited with a zinc chelator. There was an increase in the expression of migratory markers MYL9 and CYR61 in ZIP9 cells. This rise was further accompanied by increased cell migration when forskolin was administered, and H-89 was used to prevent the migration. It suggested that these markers are mediated via an AC/PKA pathway. 

The expression of ZIP9 was knocked down in MDA-MB-468 cells, which reduced cell migration and invasion, migration markers, and zinc levels. The finding established that unliganded ZIP9 functions similarly in another breast cancer cell line. In ZIP9 cells, testosterone therapy increased migration, biomarker expression, and zinc levels, suggesting that testosterone may cause tumorigenic responses via mechanisms comparable to those already present.

Source: sciencedirect.com/science/article/abs/pii/S0303720723002113