Increased DEF6 expression is correlated with metastasis and poor prognosis in human osteosarcoma

Abstract

Metastasis is the primary cause of high mortality in patients with osteosarcoma (OS). However, the molecular mechanisms underlying the regulation of metastatic disease are yet to be determined. Differentially expressed in FDCP 6 homolog (DEF6) has been demonstrated to be correlated with the metastatic behavior of several cancers, such as breast, ovarian and colorectal cancers. However, the role of DEF6 in OS remains unknown. Accordingly, the current study aimed to investigate the relationship between DEF6 expression and the malignant behavior of OS. The results revealed that high levels of DEF6 in OS tissues were associated with advanced clinical stage and metastases. Furthermore, immunohistochemistry results predicted a poor prognosis in 58 human OS specimens. Additionally, DEF6 expression was reported to be upregulated in human OS cell lines compared with a normal osteoblast cell line. small interfering RNA transfection, cell proliferation and colony formation assays, wound healing assays and Transwell assays were performed. DEF6 was not identified to be a major driver of OS cell proliferation, but it significantly contributed to metastatic potential in vitro. In addition, bioinformatics, western blotting and immunohistochemistry results indicated that MMP9 expression was positively correlated with DEF6 expression in human OS. To summarize, the results revealed that increased levels of DEF6 were associated with metastasis and poor prognosis in human OS and that DEF6 expression is positively correlated with MMP9 expression. The results indicated that DEF6 may serve as a potential antimetastatic target for OS.