Estrogens Determine Adherens Junction Organization and E-Cadherin Clustering in Breast Cancer Cells via Amphiregulin

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Philip Bischoff - , Federal Institute for Risk Assessment, Charité – Universitätsmedizin Berlin (Author)
  • Marja Kornhuber - , Federal Institute for Risk Assessment, Free University of Berlin (Author)
  • Sebastian Dunst - , Dresden International Graduate School for Biomedicine and Bioengineering, Federal Institute for Risk Assessment (Author)
  • Jakob Zell - , Federal Institute for Risk Assessment, Charité – Universitätsmedizin Berlin (Author)
  • Beatrix Fauler - , Max Planck Institute for Molecular Genetics (Author)
  • Thorsten Mielke - , Max Planck Institute for Molecular Genetics (Author)
  • Anna V. Taubenberger - , Oncomechanics (Research Group) (Author)
  • Jochen Guck - , Max Planck Institute for Molecular Genetics (Author)
  • Michael Oelgeschläger - , Federal Institute for Risk Assessment (Author)
  • Gilbert Schönfelder - , Federal Institute for Risk Assessment, Charité – Universitätsmedizin Berlin (Author)

Abstract

Estrogens play an important role in the development and progression of human cancers, particularly in breast cancer. Breast cancer progression depends on the malignant destabilization of adherens junctions (AJs) and disruption of tissue integrity. We found that estrogen receptor alpha (ERα) inhibition led to a striking spatial reorganization of AJs and microclustering of E-Cadherin (E-Cad) in the cell membrane of breast cancer cells. This resulted in increased stability of AJs and cell stiffness and a reduction of cell motility. These effects were actomyosin-dependent and reversible by estrogens. Detailed investigations showed that the ERα target gene and epidermal growth factor receptor (EGFR) ligand Amphiregulin (AREG) essentially regulates AJ reorganization and E-Cad microclustering. Our results not only describe a biological mechanism for the organization of AJs and the modulation of mechanical properties of cells but also provide a new perspective on how estrogens and anti-estrogens might influence the formation of breast tumors.

Details

Original languageEnglish
Article number101683
JournaliScience
Volume23
Issue number11
Publication statusPublished - 20 Nov 2020
Peer-reviewedYes

External IDs

Scopus 85094579295

Keywords

Sustainable Development Goals

ASJC Scopus subject areas

    Keywords

    • Cancer, Cell Biology