CONICET | Buscador de Institutos y Recursos Humanos

Sex steroids play a key role in cell movement and tissue organization. Cell migration requires the integration of events that induce changes in cell structure like protrusion, polarization, traction and retraction to the direction of migration. These actions are usually driven by actin polymerization and they are stabilized by adhering to the extracellular matrix or adjacent cells via transmembrane receptors linked to the actin cytoskeleton. Focal Adhesion Kinase (FAK) is a pivotal modulator of adhesion turnover. FAK is a non-receptor tyrosine kinase that induces cell migration process via the control of the focal adhesion complex¡¦s disassembly and reorganize focal contacts in direction of migration. In this work we have demonstrated that 17b-estradiol (E2) regulate the actin remodelling and cell movement in human vascular endothelial cells by non genomic action that are strictly depend on the rapid activation of FAK. E2 activates FAK through Estrogen Receptor (ER) and from there begins a protein G-dependent signaling pathway. Phosphorylation of FAK is fundamental for its activation, translocation to the plasmatic membrane and subsequently formation of focal adhesion complex that are important in cell migration. The activation of this cascade takes place within some minutes from administration of estradiol and results in changes of cells morphology and in the development of specific structures of the membrane, necessary for cells movement. All these results increase our knowledge about the molecular basis of estrogens on human endothelial cells, in particular actin remodelling, movement and migration providing the molecular mechanism by which estrogen exert this action and will help to understand some of the effects of this hormone in physiological or pathological settings.

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