Suppressor of fused (Sufu) promotes epithelial-mesenchymal transition (EMT) in cervical squamous cell carcinoma
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Ziyu Zhang1,*, Yang Zou1,*, Meirong Liang1, Yuanting Chen1,2, Yong Luo1, Bicheng Yang1, Faying Liu1, Yunna Qin3, Deming He3, Feng Wang1 and Ouping Huang1
1Key Laboratory of Women's Reproductive Health of Jiangxi, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, P.R. China
2Graduate School of Nanchang University, Nanchang, Jiangxi 330031, P.R. China
3Department of Pathology, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, P.R. China
*These authors have contributed equally to this work
Feng Wang, email: [email protected]
Ouping Huang, email: [email protected]
Keywords: cervical carcinoma; Sufu; 14-3-3ζ; EMT; FoxM1
Received: January 23, 2017 Accepted: November 13, 2017 Published: December 11, 2017
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.
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