[GPER1 regulates M2 macrophage polarization through the MYC pathway to influence gastric cancer progression].

co-culture system was established to simulate tumor-macrophage interactions. Flow cytometry was used to quantify the proportion of M2 macrophages, and IL-10 secretion was measured via ELISA. Results GPER1 expression was significantly downregulated in GC tissues and showed a negative correlation with MYC signaling activity. Knockdown of GPER1 promoted malignant phenotypes in gastric cancer cells, whereas GPER1 overexpression exerted suppressive effects. Mechanistically, GPER1 inhibited M2 macrophage polarization and reduced GC cell proliferation, invasion, and migration by downregulating IL-10 expression via MYC suppression. Notably, the MYC inhibitor reversed the tumor-promoting effects induced by GPER1 knockdown and enhanced the antitumor effects of GPER1 overexpression. Conclusion GPER1 modulates macrophage M2 polarization through the MYC-IL-10 axis, thereby affecting gastric cancer progression. These findings indicate GPER1 as a potential therapeutic target for gastric cancer intervention.