The expression of SIRT1 regulates the metastaticplasticity of chondrosarcoma cells by inducing epithelial-mesenchymal transition.

SIRT1 belongs to the mammalian sirtuin family and plays an important role in deacetylating histone and nonhistone proteins. It is reported that SIRT1 is associated with tumor metastasis in several kinds of tumors. However, the effect of SIRT1 on the metastasis of chondrosarcoma cells is still unknown. In this study, we demonstrated that up and down-regulation of SIRT1 expression could significantly change the invasive and metastatic potential in chondrosarcoma cell line. Besides that, the result from the nude mice confirmed the effect of SIRT1 on metastasis of chondrosarcoma cells. Furthermore, we also found that SIRT1 effectively enhanced the metastasis by inducing epithelial-mesenchymal transition (EMT) in chondrosarcoma cells. Inhibition the expression of SIRT1 could block the incidence of metastasis and EMT in chondrosarcoma cells. In addition, we also observed that SIRT1 could enhance the expression of Twist which is a key transcriptional factor of EMT. A clinicopathological analysis showed that SIRT1 expression was significantly correlated with the poor prognosis of pelvis chondrosarcoma. Kaplan-Meier survival curves revealed that positive SIRT1 expression was associated with poor prognosis in patients with pelvis chondrosarcoma. Taken together, these results indicate that SIRT1 may promote the metastasis of chondrosarcoma by inducing EMT and can be a potential molecular target for chondrosarcoma therapy.