SOX18 exerts tumor-suppressive functions in papillary thyroid carcinoma through inhibition of Wnt/β-catenin signaling
SOX18 exerts tumor-suppressive functions in papillary thyroid carcinoma through inhibition of Wnt/β-catenin signaling
复制标题
SOX18 通过抑制 Wnt/β-catenin 信号传导在甲状腺乳头状癌中发挥肿瘤抑制功能
DOI：
10.1016/j.yexcr.2020.112249
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发表时间：
2020-11-01
影响因子：
3.7
通讯作者：
Cui, Feibo
中科院分区：
文献类型：
--
作者：
Geng, Qianqian;Deng, Huixing;Cui, Feibo
性别决定区Y染色体相关的高迁移率族蛋白18（SOX 18）已成为一个关键的肿瘤相关蛋白在广泛的人类肿瘤。然而，SOX 18在甲状腺乳头状癌中的参与尚未确定。本研究旨在探讨SOX 18在甲状腺乳头状癌中的表达及其生物学功能。SOX 18在甲状腺乳头状癌组织中的表达明显低于正常甲状腺组织。在甲状腺乳头状癌细胞系中也检测到SOX 18的低表达，并且SOX 18的上调有效地抑制了甲状腺乳头状癌细胞在体外的增殖、集落形成和侵袭能力。相反，甲状腺乳头状癌细胞中SOX 18的敲低与细胞增殖和侵袭的显著增加相关。进一步的研究表明，SOX 18上调与甲状腺癌细胞中β-catenin的核积累减少和Wnt/β-catenin信号转导的下调有关。此外，Wnt/β-连环蛋白信号的抑制显着减弱SOX 18敲低诱发的甲状腺乳头状癌细胞的致癌作用。此外，SOX 18过表达显著延缓了乳头状甲状腺癌细胞来源的裸鼠异种移植瘤的肿瘤生长。综上所述，这些结果表明，SOX 18通过抑制Wnt/β-连环蛋白信号传导抑制甲状腺乳头状癌的增殖和侵袭。我们的研究揭示了SOX 18在甲状腺乳头状癌中的肿瘤抑制作用，并表明SOX 18是治疗甲状腺乳头状癌的一个有吸引力的候选靶点。
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 beta-catenin and the downregulation of Wnt/beta-catenin signaling in thyroid carcinoma cells. Moreover, inhibition of Wnt/beta-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/beta-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.