| Autor: |
Alday-Parejo B; Laboratory of Experimental and Translational Oncology, Pathology, Department of Oncology, Microbiology and Immunology, Faculty of Sciences and Medicine, University of Fribourg, Fribourg, Switzerland., Ghimire K; Laboratory of Experimental and Translational Oncology, Pathology, Department of Oncology, Microbiology and Immunology, Faculty of Sciences and Medicine, University of Fribourg, Fribourg, Switzerland.; Westmead Institute for Medical Research, University of Sydney, Sydney, Australia., Coquoz O; Laboratory of Experimental and Translational Oncology, Pathology, Department of Oncology, Microbiology and Immunology, Faculty of Sciences and Medicine, University of Fribourg, Fribourg, Switzerland., Albisetti GW; Laboratory of Experimental and Translational Oncology, Pathology, Department of Oncology, Microbiology and Immunology, Faculty of Sciences and Medicine, University of Fribourg, Fribourg, Switzerland.; Institute of Pharmacology and Toxicology, Section of Neuropharmacology, University of Zürich, Zürich, Switzerland., Tamò L; Laboratory of Experimental and Translational Oncology, Pathology, Department of Oncology, Microbiology and Immunology, Faculty of Sciences and Medicine, University of Fribourg, Fribourg, Switzerland.; Clinical Trials Unit, University of Bern, Bern, Switzerland., Zaric J; Laboratory of Experimental and Translational Oncology, Pathology, Department of Oncology, Microbiology and Immunology, Faculty of Sciences and Medicine, University of Fribourg, Fribourg, Switzerland.; Swiss Institute for Experimental Cancer Research, Ecole Polytechnique Fédérale De Lausanne, Lausanne, Switzerland., Stalin J; Laboratory of Experimental and Translational Oncology, Pathology, Department of Oncology, Microbiology and Immunology, Faculty of Sciences and Medicine, University of Fribourg, Fribourg, Switzerland., Rüegg C; Laboratory of Experimental and Translational Oncology, Pathology, Department of Oncology, Microbiology and Immunology, Faculty of Sciences and Medicine, University of Fribourg, Fribourg, Switzerland. |
| Abstrakt: |
MAGI1 is an intracellular adaptor protein that stabilizes cell junctions and regulates epithelial and endothelial integrity. Here, we report that that in endothelial cells MAGI1 colocalizes with paxillin, β3-integrin, talin 1, tensin 3 and α-4-actinin at mature focal adhesions and actin stress fibers, and regulates their dynamics. Downregulation of MAGI1 reduces focal adhesion formation and maturation, cell spreading, actin stress fiber formation and RhoA/Rac1 activation. MAGI1 silencing increases phosphorylation of paxillin at Y118, an indicator of focal adhesion turnover. MAGI1 promotes integrin-dependent endothelial cells adhesion to ECM, reduces invasion and tubulogenesis in vitro and suppresses angiogenesis in vivo . Our results identify MAGI1 as anovel component of focal adhesions, and regulator of focal adhesion dynamics, cell adhesion, invasion and angiogenesis. |
