PADI4 Modulates the Invasion and Migration of Osteosarcoma Cells by Down-regulation of Epithelial-mesenchymal Transition

Osteosarcoma (OS) is the most common type of primary bone malignancy with high recurrence and metastasis. Peptidylarginine deiminase 4 (PADI4), as an important protein post-translational modification enzyme, has been identified as a potential regulator in the invasion and migration in several types of tumors. The role of PADI4 in osteosarcoma metastasis remains unknown. In this study, we revealed significant positive correlation between PADI4 and pulmonary metastasis of osteosarcoma. Wound-healing and transwell assay indicated that PADI4 induced invasion and migration of osteosarcoma cell in vitro while PADI4 inhibitor has repressive effect. PADI4 mutation with no deimination activity exhibited no significant effect on invasion and migration of osteosarcoma cells. Moreover, we evaluated the effect of PADI4 on expression of the markers of epithelial-mesenchymal transition and results showed that PADI4 promoted EMT while PADI4 inhibitor suppressed EMT in osteosarcoma cells. We also detected the expression of PADI4 and E-Cadherin in the tissues of osteosarcoma patients with or without pulmonary metastasis. Results showed positive relationship between the expression of PADI4 and osteosarcoma metastasis. In contrast, the expression of E-Cadherin exhibited negative correlation with PADI4 and osteosarcoma metastasis. Our research offered a novel link between PADI4 and osteosarcoma metastasis and demonstrated PADI4 as a promising target for treatment of osteosarcoma metastasis.