Chu Ryan, Liu Shirley Y W, Vlantis Alexander C, van Hasselt C Andrew, Ng Enders K W, Fan Michael Dahua, Ng Siu Kwan, Chan Amy B W, Du Jing, Wei Wei, Liu Xiaoling, Liu Zhimin, Chen George G
Department of Otorhinolaryngology, Head and Neck Surgery, Prince of Wales Hospital, Shatin, NT, Hong Kong, China.
Department of Surgery, Prince of Wales Hospital, Shatin, NT, Hong Kong, China.
Mol Cell Endocrinol. 2015 Jan 5;399:228-34. doi: 10.1016/j.mce.2014.10.006. Epub 2014 Oct 12.
Foxp3+ regulatory T cells (Tregs) in lymphocytes facilitate the thyroid tumor growth and invasion. Very limited information is available on Foxp3 expression in thyroid cancer cells and its function is totally unknown. This study demonstrated that Foxp3 expression was increased in thyroid cancer cells. Inhibition of Foxp3 decreased cell proliferation and migration, but increased apoptosis, suggesting a positive role of Foxp3 in cancer growth. Interestingly, Foxp3 inhibition enhanced PPARγ expression and activity. In addition, Foxp3 inhibition downregulated NF-κB subunit p65 and cyclin D1 but upregulated caspase-3 levels. These molecular changes are in line with Foxp3 shRNA-mediated alteration of cell functions. Collectively, our study demonstrates that thyroid cancer cells express a high level of functional Foxp3 and that the inhibition of the Foxp3 suppresses the proliferation and migration but promotes apoptosis, suggesting that targeting Foxp3 in thyroid cancer cells may offer a novel therapeutic option for thyroid cancer.
淋巴细胞中的Foxp3 +调节性T细胞（Tregs）促进甲状腺肿瘤的生长和侵袭。关于甲状腺癌细胞中Foxp3表达的信息非常有限，其功能也完全未知。本研究表明，甲状腺癌细胞中Foxp3表达增加。抑制Foxp3可降低细胞增殖和迁移，但增加细胞凋亡，提示Foxp3在癌症生长中起积极作用。有趣的是，抑制Foxp3可增强PPARγ的表达和活性。此外，抑制Foxp3可下调NF-κB亚基p65和细胞周期蛋白D1，但上调caspase-3水平。这些分子变化与Foxp3 shRNA介导的细胞功能改变一致。总的来说，我们研究表明甲状腺癌细胞表达高水平的功能性Foxp3，抑制Foxp3可抑制增殖和迁移，但促进凋亡，提示靶向甲状腺癌细胞中的Foxp3可能为甲状腺癌提供一种新的治疗选择。
