Zhang Ziyu, Zou Yang, Liang Meirong, Chen Yuanting, Luo Yong, Yang Bicheng, Liu Faying, Qin Yunna, He Deming, Wang Feng, Huang Ouping
Key Laboratory of Women's Reproductive Health of Jiangxi, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, P.R. China.
Graduate School of Nanchang University, Nanchang, Jiangxi 330031, P.R. China.
Oncotarget. 2017 Dec 11;8(69):114226-114238. doi: 10.18632/oncotarget.23176. eCollection 2017 Dec 26.
Suppressor of fused is essential for the maximal activation of Sonic Hedgehog signaling in development and tumorigenesis. However, the role of Sufu in cervical carcinoma remains unknown. Here, we report new findings of Sufu in regulating the epithelial-to-mesenchymal transition through the FoxM1 transcriptional modulation by 14-3-3ζ protein in cervical carcinoma. Sufu is overexpressed in cervical squamous cell carcinoma and its level in clinical tumor tissues is positively correlated with 14-3-3ζ. Functionanlly, siSufu remarkably prevents the cancer cell migration and invasion. We further demonstrate that the transcriptional activity of Sufu is increased by FoxM1, of which stability is promoted by 14-3-3ζ. Knockdown FoxM1 decreases the invasion of SiHa cells and reconstitution of Sufu rescues the invasion of these cells.Finally, overexpression of Sufu is significantly associated with differentiation grade, FIGO stage, Depth of stromal invasion and vascular cancer embolus. Our findings highlight a novel role for Sufu in cervical carcinogenesis.
融合抑制因子对于发育和肿瘤发生过程中 Sonic Hedgehog 信号通路的最大激活至关重要。然而，Sufu 在宫颈癌中的作用仍不清楚。在此，我们报告了 Sufu 在宫颈癌中通过 14-3-3ζ 蛋白对 FoxM1 转录调节来调控上皮-间质转化的新发现。Sufu 在宫颈鳞状细胞癌中过表达，其在临床肿瘤组织中的水平与 14-3-3ζ 呈正相关。功能上，siSufu 显著抑制癌细胞迁移和侵袭。我们进一步证明，FoxM1 增加了 Sufu 的转录活性，而 14-3-3ζ 促进了 Sufu 的稳定性。敲低 FoxM1 可降低 SiHa 细胞的侵袭，而恢复 Sufu 可挽救这些细胞的侵袭。最后，Sufu 的过表达与分化程度、国际妇产科联盟（FIGO）分期、间质浸润深度和血管癌栓显著相关。我们的发现突出了 Sufu 在宫颈癌发生中的新作用。
