RAF dimers control vascular permeability and cytoskeletal rearrangements at endothelial cell‐cell junctions

• DOI: 10.1111/febs.14802
• Publication Date: 2019-03-04T07:26:02Z
• Authors: Coralie Dorard; Botond Cseh; Karin Ehrenreiter; Reiner Wimmer; Andrea Varga; Tatjana Hirschmugl; Barbara Maier; Karina Kramer; Sabine Fürlinger; Eszter Doma; Manuela Baccarini
• Keywords: Vascular permeability

The endothelium functions as a semipermeable barrier regulating fluid homeostasis, nutrient, and gas supply to the tissue. Endothelial permeability is increased in several pathological conditions including inflammation tumors; despite its clinical relevance, however, there are no specific therapies preventing vascular leakage. Here, we show that endothelial cell‐restricted ablation of BRAF , kinase frequently activated cancer, prevents leaking well metastatic spread. regulates by promoting cytoskeletal rearrangements necessary for remodeling VE ‐Cadherin‐containing cell–cell junctions formation intercellular gaps. activity ability form complexes with RAS / RAP 1 dimers paralog RAF required proper control, achieved mechanistically modulating interaction between RHO effector ROK α. Thus, dimerization impinges on pathways regulate rearrangements, junctional plasticity, permeability. data advocate development inhibitors, which would combine tumor cell autonomous effect stabilization vasculature antimetastatic