Suppressor of fused (Sufu) promotes epithelial-mesenchymal transition (EMT) in cervical squamous cell carcinoma

Abstract

// Ziyu Zhang 1, * , Yang Zou 1, * , Meirong Liang 1 , Yuanting Chen 1, 2 , Yong Luo 1 , Bicheng Yang 1 , Faying Liu 1 , Yunna Qin 3 , Deming He 3 , Feng Wang 1 and Ouping Huang 1 1 Key Laboratory of Women's Reproductive Health of Jiangxi, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, P.R. China 2 Graduate School of Nanchang University, Nanchang, Jiangxi 330031, P.R. China 3 Department of Pathology, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, P.R. China * These authors have contributed equally to this work Correspondence to: Feng Wang, email: jxwangfeng@126.com Ouping Huang, email: jxhop59@126.com Keywords: cervical carcinoma; Sufu; 14-3-3ζ; EMT; FoxM1 Received: January 23, 2017      Accepted: November 13, 2017      Published: December 11, 2017 ABSTRACT 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.