By analyzing 18 pairs of GC tissues and establishing in vitro models (combining GLIS2 knockdown/BGN overexpression with Wnt pathway modulators), we demonstrated that GLIS2 directly binds to the BGN promoter to enhance its transcription, thereby activating Wnt/β-catenin signaling and significantly promoting GC cell migration, invasion, and EMT. The gene discussed is BGN; the disease is gastric cancer.