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YAP1 inhibits ovarian endometriosis stromal cell invasion through ESR2

Cheng Zeng1, Pei-Li Wu1, Zhao-Tong Dong1

  • 1Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing, China.

Reproduction (Cambridge, England)
|June 17, 2020
PubMed

Insights

Decreased Yes-associated protein 1 (YAP1) in ovarian endometriosis enhances estrogen receptor 2 (ESR2) expression, promoting cell invasion. YAP1 normally inhibits endometriotic stromal cell invasion, but its reduced levels lead to increased ESR2, driving disease progression.

Area of Science:

  • Gynecology
  • Cell Biology
  • Molecular Biology

Background:

  • Endometriosis is an estrogen-dependent condition where estrogen receptor 2 (ESR2) promotes ovarian lesion invasion.
  • Yes-associated protein 1 (YAP1) typically suppresses tumor growth, but its role in endometriosis, particularly its interaction with ESR2, is unclear.

Purpose of the Study:

  • To investigate the regulatory relationship between YAP1 and ESR2 in ovarian endometriosis.
  • To elucidate the mechanism by which YAP1 influences endometriotic stromal cell (ECSC) invasion.

Main Methods:

  • Quantitative analysis of YAP1 and ESR2 in eutopic and ectopic endometrial tissues.
  • In vitro studies using small interfering RNA (siRNA) to knockdown YAP1 and ESR2 in ECSCs.
  • Co-immunoprecipitation (Co-IP) assays to identify YAP1-interacting protein complexes.
  • Chromatin immunoprecipitation (ChIP) assays to determine YAP1 binding sites on the ESR2 promoter.

Main Results:

  • YAP1 levels were lower in ectopic endometrial tissues compared to eutopic tissues.
  • Knockdown of YAP1 increased ESR2 expression and ECSC invasion, while YAP1 overexpression had opposite effects.
  • YAP1 formed a complex with NuRD components (CHD4, MTA1) and bound to specific sites on the ESR2 promoter.
  • YAP1 binding to the ESR2 promoter was reduced in ECSCs compared to eutopic endometrial stromal cells (EUSCs).

Conclusions:

  • Reduced YAP1 in ovarian endometriomas leads to increased ESR2 expression through YAP1-NuRD complex binding to ESR2 promoters.
  • YAP1 plays an inhibitory role in ECSC invasion, and its downregulation contributes to endometriosis pathogenesis.

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