IBSP Promotes Breast Cancer Bone Metastasis and Proliferation via BMP-SMAD Signaling Pathway.

BACKGROUND: Integrin-Binding Sialoprotein (IBSP) has been implicated in tumor progression across various cancers. However, the specific role of IBSP in breast cancer remains underexplored. There is a need to investigate the mechanisms by which IBSP influences breast cancer progression and its potential as a therapeutic target. AIMS: This study aims to elucidate the role of IBSP in breast cancer, particularly its impact on tumor progression and its relationship with prognosis. We also seek to understand the underlying mechanisms, including the involvement of the BMP-SMAD signaling pathway, and to explore the potential of targeting IBSP for therapeutic interventions. METHODS AND RESULTS: Overexpression of IBSP in breast cancer cells led to increased migration and invasion, whereas IBSP interference reduced these behaviors, indicating its role in enhancing tumor progression. Differentially expressed genes were significantly enriched in the BMP-SMAD signaling pathway, a critical pathway for osteogenic differentiation. Transcription Factor Binding: Dual luciferase reporter assays demonstrated that SMAD4 specifically binds to the IBSP promoter, establishing a regulatory link between SMAD4 and IBSP expression. Silencing IBSP (si-IBSP) mitigated the effects of SMAD4-induced tumor proliferation, confirming that IBSP acts as a downstream target of SMAD4 in the BMP signaling pathway. CONCLUSION: Our study reveals that IBSP plays a significant role in breast cancer progression through the BMP-SMAD4 signaling pathway. Targeting IBSP could be a promising therapeutic strategy for breast cancer treatment. Further research into IBSP inhibitors may offer new avenues for improving treatment outcomes and managing breast cancer more effectively.