Abnormal expression of p63 has been well identified in multiple malignancies. However, little study has been done on the association between p63 and chondro sarcoma. In the current study, we mainly explored the expression of p63 in different grades of chondrosarcoma. Our data showed that p63 was significantly decreased in grade II and III chondrosarcoma compared with that of grade I chondrosarcoma and normal control. As the characteristic of grade II and III chondrosarcoma is metastasis, we then searched the function of p63 chondrosarcoma. In vitro study showed that overexpression of p63 significantly suppressed chondrosarcoma cell viability, migration and invasion. Meanwhile, upregualtion of p63 induced chondrosarcoma cell apoptosis. Furthermore, we showed that overexpression of p63 could significantly increase the protein expression of PTEN. In contrast, silencing of PTEN markedly reduced the protein levels of Bax, and enhanced the expression of PCNA and p27, even in cells transfected with p-p63. These data showed that p63 was a tumor suppressor mainly through regulating PTEN in chondrosarcoma cells. In summary, reduction of p63 in grade II and III chondrosarcoma enhances the malignant phenotype mainly through modulating the expression of PTEN.

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