FOXQ1 activates GLT8D2 to enhance CCL2 N-glycosylation and promote prostate cancer bone metastasis.

Prostate cancer (PCa) is a common malignancy in men, and bone metastasis is a leading cause of mortality in advanced-stage PCa. This study aims to identify critical genes involved in PCa bone metastasis, exploring biomarkers for prognosis and precision treatment. Forkhead Box Q1 (FOXQ1) was identified as a potential key gene through screening of public databases, and was found to be markedly upregulated in bone metastatic PCa compared to primary PCa. FOXQ1 promotes PCa cell proliferation and metastasis while inhibiting apoptosis. Additionally, FOXQ1 recruits macrophages, promotes M2 polarization, and enhances osteoclast differentiation in the tumor microenvironment. Mechanistically, FOXQ1 activates the transcription of Glycosyltransferase 8 Domain Containing 2 (GLT8D2) by directly binding to its promoter, and GLT8D2 upregulates the expression of C-C Motif Chemokine Ligand 2 (CCL2) by enhancing its N-glycosylation, thereby promoting PCa bone metastasis. Collectively, these findings establish FOXQ1 as a key regulator of PCa bone metastasis through the GLT8D2/CCL2 axis, and suggest that targeting this pathway may hold therapeutic promise for bone metastatic PCa.