摘要Medulloblastoma(MB)is the most common malignant tumor of the cerebellum in children.The Sonic Hedgehog(SHH)subgroup of MB(SHH-MB)is driven by aberrant activation of the SHH pathway;however,mutations in genes related to this pathway are relatively rare,posing challenges for therapeutic development.Glypican-6(GPC6),a heparan sulfate proteoglycan,is highly expressed in SHH-MB.In this study,we demonstrate the synchronous expression of GPC6 with GLI family zinc finger 1(GLI1)in both the developing cerebellum and medulloblastoma.GPC6 promotes cell proliferation,migration,and invasion in SHH-MB cell lines(DAOY and ONS-76).Consistently,GPC6 enhances the SHH pathway activity by upregulating GLI1 expression,supports ciliogenesis essential for signal transduction,and facilitates SHH ligand expression via extracellular vesicles.These findings suggest that GPC6 acts as a key regulator of SHH signaling and represents a potential therapeutic target in SHH-MB.