E2 -mediated EMT by activation of β-catenin/Snail signalling during the development of ovarian endometriosis

J Cell Mol Med. 2019 Dec;23(12):8035-8045. doi: 10.1111/jcmm.14668. Epub 2019 Sep 27.

Abstract

Endometriosis is an oestrogen-dependent disease, and epithelial-mesenchymal transition (EMT) is involved in the process of endometriosis. Whether oestrogen could induce EMT in endometriosis remains largely unknown. Here, we reported that up-regulated expression of EMT markers in ovarian chocolate cyst is accompanied by high expression 17β-hydroxysteroid dehydrogenase 1 (17β-HSD1), and exposure of primary human endometrial epithelial cells to oestradiol conditions could promote EMT occurrence and activate both β-catenin and Snail signalling. Furthermore, we found nuclear β-catenin and Snail expression was closely linked in ovarian endometriosis, and β-catenin knockdown abrogated oestrogen-induced Snail mediated EMT in vitro. This is due to that β-catenin/ TCF-3 could bind to Snail promoter and activate its transcription. These results suggested that β-catenin signalling functions as the Snail activator and plays a critical role in oestradiol-induced EMT in endometriosis.

Keywords: ICI; endometriosis; epithelial-mesenchymaltransition; oestrogen; β-catenin/Snail signalling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 17-Hydroxysteroid Dehydrogenases / metabolism
  • Adult
  • Cadherins / metabolism
  • Cell Movement / drug effects
  • Cells, Cultured
  • Chromatin Immunoprecipitation
  • Endometriosis / etiology
  • Endometriosis / metabolism*
  • Endometrium / cytology
  • Endometrium / drug effects
  • Endometrium / metabolism
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Epithelial-Mesenchymal Transition* / drug effects
  • Estradiol / pharmacology
  • Estradiol / physiology*
  • Estrogens / pharmacology
  • Female
  • Humans
  • Ovarian Cysts / metabolism*
  • RNA, Small Interfering
  • Receptors, Estrogen / antagonists & inhibitors
  • Signal Transduction / drug effects
  • Snail Family Transcription Factors / metabolism*
  • Up-Regulation
  • beta Catenin / metabolism*

Substances

  • Cadherins
  • Estrogens
  • RNA, Small Interfering
  • Receptors, Estrogen
  • Snail Family Transcription Factors
  • beta Catenin
  • Estradiol
  • 17-Hydroxysteroid Dehydrogenases