Estrogens Determine Adherens Junction Organization and E-Cadherin Clustering in Breast Cancer Cells via Amphiregulin
Philip Bischoff,
Marja Kornhuber,
Sebastian Dunst,
Jakob Zell,
Beatrix Fauler,
Thorsten Mielke,
Anna V. Taubenberger,
Jochen Guck,
Michael Oelgeschläger,
Gilbert Schönfelder
Affiliations
Philip Bischoff
German Federal Institute for Risk Assessment (BfR), German Centre for the Protection of Laboratory Animals (Bf3R), Max-Dohrn-Straße 8-10, 10589 Berlin, Germany; Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
Marja Kornhuber
German Federal Institute for Risk Assessment (BfR), German Centre for the Protection of Laboratory Animals (Bf3R), Max-Dohrn-Straße 8-10, 10589 Berlin, Germany; Freie Universität Berlin, 14195 Berlin, Germany
Sebastian Dunst
German Federal Institute for Risk Assessment (BfR), German Centre for the Protection of Laboratory Animals (Bf3R), Max-Dohrn-Straße 8-10, 10589 Berlin, Germany
Jakob Zell
German Federal Institute for Risk Assessment (BfR), German Centre for the Protection of Laboratory Animals (Bf3R), Max-Dohrn-Straße 8-10, 10589 Berlin, Germany; Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
Beatrix Fauler
Max Planck Institute for Molecular Genetics, Microscopy and Cryo-Electron Microscopy Service Group, 14195 Berlin, Germany
Thorsten Mielke
Max Planck Institute for Molecular Genetics, Microscopy and Cryo-Electron Microscopy Service Group, 14195 Berlin, Germany
Anna V. Taubenberger
Biotechnology Center, Technische Universität Dresden, 01307 Dresden, Germany
Jochen Guck
Max Planck Institute for the Science of Light, Max-Planck-Zentrum für Physik und Medizin, 91058 Erlangen, Germany
Michael Oelgeschläger
German Federal Institute for Risk Assessment (BfR), German Centre for the Protection of Laboratory Animals (Bf3R), Max-Dohrn-Straße 8-10, 10589 Berlin, Germany
Gilbert Schönfelder
German Federal Institute for Risk Assessment (BfR), German Centre for the Protection of Laboratory Animals (Bf3R), Max-Dohrn-Straße 8-10, 10589 Berlin, Germany; Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany; Corresponding author
Summary: 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.
