title: EFEMP1 is repressed by estrogen and inhibits the epithelial-mesenchymal transition via Wnt/β-catenin signaling in endometrial carcinoma.
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.
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai First People's Hospital Affiliated to Nanjing Medical University, Nanjing, China.|Center for Reproductive Medicine, Affiliated Hospital of Weifang Medical University, Weifang, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai First People's Hospital Affiliated to Nanjing Medical University, Nanjing, China.|Department of Gynecology and Obstetrics, Nanjing Maternal and Children Care Hospital Affiliated to Nanjing Medical University, Nanjing, China.
authors.forename: Huilin
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai First People's Hospital Affiliated to Nanjing Medical University, Nanjing, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Qiu
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Bilan
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Jingyun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Guiqiang
authors.initials: G
authors.lastname: Du
authors.affiliation: Center for Reproductive Medicine, Affiliated Hospital of Weifang Medical University, Weifang, China.
authors.forename: Chune
authors.initials: C
authors.lastname: Ren
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai First People's Hospital Affiliated to Nanjing Medical University, Nanjing, China.|Department of Obstetrics and Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Wan
mesh_terms: D000818:Animals; D016889:Endometrial Neoplasms / Q000378:metabolism / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D064593:Heterografts; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D060449:Wnt Signaling Pathway / Q000502:physiology*
chemical_list: C119630:EFEMP1 protein, human; D047628:Estrogen Receptor alpha; D004967:Estrogens; D016326:Extracellular Matrix Proteins
keywords: EFEMP1; Wnt/β-catenin; endometrial carcinoma (EC); epithelial-mesenchymal transition (EMT); estrogen receptor α (ERα)