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Updated: Apr 23, 2026

Modeling the Early Steps of Ovarian Cancer Dissemination in an Organotypic Culture of the Human Peritoneal Cavity
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Amphiregulin induces human ovarian cancer cell invasion by down-regulating E-cadherin expression

Wai-Kin So1, Qianlan Fan1, Man-Tat Lau1

  • 1Department of Obstetrics and Gynecology, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada.

FEBS Letters
|September 28, 2014
PubMed

Insights

Amphiregulin (AREG) drives ovarian cancer cell invasion by reducing E-cadherin. This EGFR ligand activates SNAIL, SLUG, and ZEB1, promoting cancer cell migration and metastasis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Aberrant epidermal growth factor receptor (EGFR) signaling is implicated in ovarian cancer progression.
  • EGFR ligands play crucial roles in cancer cell behavior.

Purpose of the Study:

  • To investigate the role of the EGFR ligand amphiregulin (AREG) in ovarian cancer cell invasion and E-cadherin expression.
  • To elucidate the molecular mechanisms underlying AREG-mediated effects.

Main Methods:

  • Utilized human ovarian cancer cell lines (SKOV3, OVCAR5).
  • Assessed cell invasion, E-cadherin expression, and transcriptional repressor levels (SNAIL, SLUG, ZEB1).
  • Employed siRNA to target SNAIL and SLUG; investigated ERK1/2 and AKT pathway involvement.

Main Results:

  • AREG significantly stimulated cell invasion and decreased E-cadherin expression in ovarian cancer cells.
  • AREG upregulated SNAIL, SLUG, and ZEB1, which are transcriptional repressors of E-cadherin.
  • siRNA-mediated knockdown of SNAIL or SLUG abrogated AREG-induced invasion.
  • ERK1/2 and AKT signaling pathways were found to be involved in AREG's effects.
  • AREG, EGF, and TGF-α demonstrated similar capacities to down-regulate E-cadherin and promote invasion.

Conclusions:

  • AREG is a key mediator of ovarian cancer cell invasion through the downregulation of E-cadherin.
  • The study highlights the involvement of SNAIL, SLUG, ERK1/2, and AKT pathways in this process.
  • Multiple EGFR ligands share the ability to promote ovarian cancer cell invasion, underscoring the significance of EGFR signaling in metastasis.
Keywords:
AmphiregulinE-cadherinInvasionOvarian cancer

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