SOX18 exerts tumor-suppressive functions in papillary thyroid carcinoma through inhibition of Wnt/β-catenin signaling

Abstract

Sex-determining region on the Y chromosome-related high mobility group box 18 (SOX18) has emerged as a key tumor-related protein in a wide range of human tumors. Yet, the involvement of SOX18 in papillary thyroid carcinoma has not been determined. This study aimed to explore the expression and biological function of SOX18 in papillary thyroid carcinoma. There was a significant decrease in SOX18 expression in papillary thyroid carcinoma tissues compared with that in normal tissues. Low expression of SOX18 was also detected in papillary thyroid carcinoma cell lines and upregulation of SOX18 effectively repressed the proliferative, colony-forming and invasive abilities of papillary thyroid carcinoma cells in vitro. In contrast, knockdown of SOX18 in papillary thyroid carcinoma cells was associated with a significant increase in cell proliferation and invasion. Further studies revealed that SOX18 upregulation was associated with the reduced nuclear accumulation of β-catenin and the downregulation of Wnt/β-catenin signaling in thyroid carcinoma cells. Moreover, inhibition of Wnt/β-catenin signaling markedly attenuated SOX18 knockdown-evoked oncogenic effects in papillary thyroid carcinoma cells. In addition, SOX18 overexpression remarkably retarded the tumor growth of papillary thyroid carcinoma cell-derived xenograft tumors in nude mice. Taken together, these results demonstrate that SOX18 suppresses the proliferation and invasion of papillary thyroid carcinoma by inhibiting Wnt/β-catenin signaling. Our study reveals a tumor-suppressive role of SOX18 in papillary thyroid carcinoma and suggests that SOX18 is an attractive candidate target for treatment of papillary thyroid carcinoma.