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Amphiregulin Downregulates E-cadherin Expression by Activating YAP/Egr-1/Slug Signaling in SKOV3 Human Ovarian Cancer

Qiongqiong Jia1,2, Hailong Wang1, Beibei Bi1

  • 1Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Reproductive Sciences (Thousand Oaks, Calif.)
|August 14, 2024
PubMed

Insights

Amphiregulin (AREG) drives ovarian cancer invasion by reducing E-cadherin via YAP activation. This pathway, involving Egr-1 and Slug, highlights YAP as a therapeutic target for epithelial ovarian cancer (EOC).

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Amphiregulin (AREG) is implicated in epithelial ovarian cancer (EOC) progression.
  • Yeast-retroviral protein-associated (YAP) is a transcriptional cofactor involved in tumorigenesis.
  • AREG's role in YAP activation and its downstream effects in EOC remain unclear.

Purpose of the Study:

  • To investigate if AREG activates YAP in EOC cells.
  • To explore YAP's role in AREG-induced E-cadherin downregulation and cell invasion.
  • To elucidate the signaling pathway linking AREG, YAP, and EOC cell invasion.

Main Methods:

  • Analysis of The Cancer Genome Atlas (TCGA) data for AREG and EGFR correlations with EOC survival.
  • Treatment of SKOV3 EOC cells with AREG to assess YAP activation, E-cadherin, Egr-1, and Slug expression.
  • Gain- and loss-of-function experiments to determine YAP's necessity in AREG-mediated effects.

Main Results:

  • TCGA analysis revealed AREG and EGFR upregulation correlates with poor EOC survival.
  • AREG treatment activated YAP, downregulated E-cadherin, upregulated Egr-1 and Slug, and increased EOC cell invasion.
  • YAP was essential for AREG-induced Egr-1 and Slug expression, E-cadherin downregulation, and enhanced cell invasion.

Conclusions:

  • AREG activates YAP in human EOC cells.
  • AREG stimulates EOC cell invasion by downregulating E-cadherin.
  • The YAP/Egr-1/Slug signaling pathway mediates AREG-induced EOC cell invasion and E-cadherin suppression.
Keywords:
AmphiregulinE-cadherinEgr-1Ovarian cancerYAP

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