SLC39A10 drives M2 macrophage polarization and gastric cancer progression through the MAPK14(p38α) pathway.

The zinc transporter SLC39A10 serves as a risk factor for malignant progression in gastric cancer (GC), characterized by the formation of an immunosuppressive tumor microenvironment (TME). As key cellular components within this microenvironment, both malignant cells and macrophages are influenced by SLC39A10, yet its regulatory mechanisms at the subpopulation level remain unclear. Using single-cell RNA sequencing and functional experiments, we investigated the cell-type-specific role of SLC39A10 in GC. Results demonstrated that oeSLC39A10 tumor cells exhibit activated MAPK14 signaling pathway, while tumor-associated macrophages (TAMs) display a biased M2 polarization state. These two cell populations establish intercellular communication through secretory factors IL-10 and TGF-β, synergistically promoting tumor proliferation and angiogenesis. This study identifies an SLC39A10-MAPK14-M2 macrophage regulatory axis that critically influences immune microenvironment remodeling and GC progression. Targeting this signaling axis may provide a viable therapeutic approach to alter the TME and suppress disease advancement.