ASPSCR1 promotes osteosarcoma progression through the upregulation of glycolysis

Osteosarcoma (OS), the most common primary bone malignancy, is highly metastatic and difficult to treat. Although ASPSCR1 is implicated in multiple cancers, its role and mechanism in OS remain unclear. This study aims to clarify ASPSCR1 function in OS progression.ASPSCR1 expression and prognosis were evaluated via immunohistochemistry and statistics in clinical cohorts. Lentiviral shRNA-mediated ASPSCR1 knockdown in OS cells enabled functional assessments of proliferation, apoptosis, migration/invasion. Gene Set Enrichment Analysis (GSEA) identified pathways enrichment, further corroborated by glucose, lactate, and ATP assays. In vivo tumorigenicity was assessed using subcutaneous xenograft.ASPSCR1 was overexpressed in OS tissues and associated with poor survival. ASPSCR1 knockdown inhibited proliferation and migration while inducing apoptosis in OS cells. GSEA revealed significant enrichment of ASPSCR1-associated genes in the glycan biosynthesis. PKM2 inhibition (PKM2-IN-3) abolished ASPSCR1-driven glycolytic activity and proliferation. Consistent with in vitro findings, in vivo experiments robustly supported the pivotal role of ASPSCR1 knockdown in reducing glycolytic activity and inhibiting OS tumor growth. ASPSCR1 promotes OS progression via upregulating glycolysis, representing a potential therapeutic target.