Adaptor protein <scp>CIN85</scp> potentiates the motility of osteosarcoma cells via the Akt/ <scp>mTOR</scp> and <scp>MMP2</scp> ‐ <scp>COL3A1</scp> axis

Osteosarcoma is the most common malignant bone tumor, primarily affecting adolescents and young adults. Patients with metastases have a low survival rate, making the identification of prognostic markers crucial. The adaptor protein CIN85 is involved in various signaling pathways that regulate cell differentiation, adhesion, and motility. Its overexpression is associated with poor prognosis in multiple cancers. However, the role of CIN85 in osteosarcoma progression has not yet been explored. This study shows that CIN85 expression is higher in osteosarcoma than in normal bone tissue and further increased in metastatic lesions relative to primary tumors. CIN85 overexpression increases cell migration and Matrigel invasion, whereas silencing CIN85 suppresses these behaviors. Functional annotation and enrichment analyses of the CIN85-driven transcriptome suggest that CIN85 regulates migration, adhesion, and extracellular matrix organization in osteosarcoma. CIN85 affects MMP2 and COL3A1 gene expression and activates Akt/mTOR signaling. Knockdown of MMP2 and COL3A1 or pharmacological inhibion of Akt/mTOR signaling abrogates CIN85-induced motility. This study demonstrates that elevated CIN85 expression contributes to osteosarcoma migration and metastasis, highlighting its potential as a therapeutic target.