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WFDC2 contributes to epithelial–mesenchymal transition (EMT) by activating AKT signaling pathway and regulating MMP-2 expression

Authors Chen Y, Huang L, Wang S, Li JL, Li M, Wu Y, Liu T

Received 31 October 2018

Accepted for publication 31 January 2019

Published 27 March 2019 Volume 2019:11 Pages 2415—2424

DOI https://doi.org/10.2147/CMAR.S192950

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 3

Editor who approved publication: Dr Antonella D'Anneo


Yao Chen,1,2 Liping Huang,3 Suihai Wang,4 Ji-Liang Li,4,5 Ming Li,1 Yingsong Wu,4 Tiancai Liu4

1School of Medical Laboratory and Biotechnology, Southern Medical University, Guangzhou 510515, People’s Republic of China; 2State Key Laboratory of Organ Failure, Guangdong Provincial Key Laboratory of Tropical Disease Research, Southern Medical University, Guangzhou 510515, People’s Republic of China; 3Obstetrics and Gynecology Centre, Nanfang Hospital, Guangzhou 510515, People’s Republic of China; 4School of Biotechnology, Southern Medical University, Guangzhou 510515, People’s Republic of China; 5Faculty of Medicine and Dentistry, Institute of Translational and Stratified Medicine, University of Plymouth, Plymouth, PL6 8BU, UK

Objective: To understand the role of WFDC2 in metastasis of ovarian cancer.
Methods: By knockdown or overexpression of WFDC2, we demonstrated the role of WFDC2 in epithelial–mesenchymal transition (EMT).
Results: We demonstrated that stable knockdown of WFDC2 suppressed EMT along with the upregulation of E-cadherin and the downregulation of Vimentin. In addition, WFDC2 knockdown decreases matrix metalloproteinase-2 (MMP-2) expression in in vitro cell model and in in vivo nude mice xenografts. The correlation of WFDC2 and MMP-2 expression in the clinical sample confirmed that WFDC2 was tightly correlated with the development of tumor. More importantly, the EMT phenotype and cell invasion induced by WFDC2 overexpressing can be reversed by the siMMP-2 and P13K/AKT signaling inhibitor.
Conclusion: WFDC2 contributed to ovarian cancer metastasis and EMT as a positive regulator by activating AKT signaling pathway and inducing MMP-2 expression.

Keywords: WFCD2, ovarian cancer, metastasis, cell migration and invasion, epithelial-mesenchymal transition

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