Oncotarget

Research Papers:

EFEMP1 is repressed by estrogen and inhibits the epithelial-mesenchymal transition via Wnt/β-catenin signaling in endometrial carcinoma

Tingting Yang _, Huilin Zhang, Haifeng Qiu, Bilan Li, Jingyun Wang, Guiqiang Du and Xiaoping Wan

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Oncotarget. 2016; 7:25712-25725. https://doi.org/10.18632/oncotarget.8263

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Abstract

Tingting Yang1,3,*, Huilin Zhang1,4,*, Haifeng Qiu1, Bilan Li2, Jingyun Wang2, Guiqiang Du2, Chune Ren3, Xiaoping Wan1,2

1Department of Obstetrics and Gynecology, Shanghai First People’s Hospital Affiliated to Nanjing Medical University, Nanjing, China

2Department of Obstetrics and Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China

3Center for Reproductive Medicine, Affiliated Hospital of Weifang Medical University, Weifang, China

4Department of Gynecology and Obstetrics, Nanjing Maternal and Children Care Hospital Affiliated to Nanjing Medical University, Nanjing, China

*These authors have contributed equally to this work

Correspondence to:

Xiaoping Wan, e-mail: [email protected]

Keywords: EFEMP1, endometrial carcinoma (EC), estrogen receptor α (ERα), epithelial-mesenchymal transition (EMT), Wnt/β-catenin

Received: December 09, 2015    Accepted: March 02, 2016    Published: March 22, 2016

ABSTRACT

Epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) acted as a tumor suppressor in endometrial carcinoma (EC). However, the correlation between EFEMP1 and estrogen is unknown. Here, we reported that the expression of EFEMP1 was conversely associated with ERα in endometrial carcinoma tissues. In endometrial carcinoma cells, estrogen/ERα signaling significantly suppressed the expression of EFEMP1. Moreover, chromatin immunoprecipitation (CHIP) and dual-luciferase reporter assays demonstrate that estrogen/ERα bound to the estrogen response element (ERE) located in EFEMP1 promoter and repressed its expression. Besides, in vitro and in vivo, EFEMP1 could remarkably suppress the expression of epithelial-mesenchymal transition (EMT) markers such as Vimentin, Snail and the Wnt/β-catenin target genes like Cyclin-D1 and c-Myc, which could be restored when EFEMP1 was silenced. In addition, XAV93920 (the inhibitor of the Wnt/β-catenin pathway) blocked and LiCl (the activator of the Wnt/β-catenin pathway) enhanced the effect of EFEMP1 on EMT. In conclusion, we demonstrated that estrogen/ERα signal suppresses EFEMP1. Besides, EFEMP1 inhibits EMT via interfering the Wnt/β-catenin signaling.


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