Nuclear Medicine Department, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.
Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.
Exp Cell Res. 2020 Nov 1;396(1):112249. doi: 10.1016/j.yexcr.2020.112249. Epub 2020 Aug 25.
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.
Y 染色体相关高迁移率族蛋白 18（SOX18）在广泛的人类肿瘤中已成为关键的肿瘤相关蛋白。然而，SOX18 与甲状腺乳头状癌的关系尚未确定。本研究旨在探讨 SOX18 在甲状腺乳头状癌中的表达及生物学功能。与正常组织相比，甲状腺乳头状癌组织中 SOX18 的表达显著降低。在甲状腺乳头状癌细胞系中也检测到 SOX18 的低表达，上调 SOX18 有效抑制了甲状腺乳头状癌细胞的体外增殖、集落形成和侵袭能力。相比之下，下调 SOX18 在甲状腺乳头状癌细胞中与细胞增殖和侵袭的显著增加相关。进一步的研究表明，SOX18 的上调与甲状腺癌细胞中β-catenin 的核积累减少和 Wnt/β-catenin 信号通路的下调有关。此外，抑制 Wnt/β-catenin 信号通路显著减弱了 SOX18 下调诱导的甲状腺乳头状癌细胞的致癌作用。此外，SOX18 的过表达显著延缓了裸鼠中甲状腺乳头状癌细胞来源的异种移植瘤的肿瘤生长。总之，这些结果表明 SOX18 通过抑制 Wnt/β-catenin 信号通路抑制甲状腺乳头状癌细胞的增殖和侵袭。我们的研究揭示了 SOX18 在甲状腺乳头状癌中的肿瘤抑制作用，并表明 SOX18 是治疗甲状腺乳头状癌的一个有吸引力的候选靶点。
