Distinct roles of parafibromin in the extracellular environment, cytoplasm and nucleus of osteosarcoma cells.

Osteosarcoma (OS) is the most common primary malignant bone tumor. Parafibromin-inactivating mutations have been reported in various malignancies. In this study, the effects and relevant mechanisms of ectopic parafibromin expression were identified in the extracellular environment, cytoplasm and nucleus of OS cells. Our results indicate that parafibromin located in the nucleus can induce apoptosis and G1 phase arrest in OS cells. Parafibromin was found to suppress the MEK/ERK and PI3K/AKT signaling pathways, leading to activation of caspase 3 and caspase 9. Overall, these studies demonstrate the anti-tumor activity of parafibromin in the OS cell line, and provide insight into relevant mechanisms that may lead to novel treatments for OS.