Estrogen Receptor

SANCHEZ AM,; FLAMINI MI; ZULLINO S, ; GOPAL S,; GENAZZANI AR,; SIMONCINI T.

Roma

Congreso; 13th World Congress on Menopause.; 2011

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 and traction towards the direction of migration. These actions are driven by actin remodelling and are stabilized by the development of adhesion sites to extracellular matrix via transmembrane receptors linked to the actin cytoskeleton. Focal Adhesion Kinase (FAK) is a non-receptor tyrosine kinase that facilitates cell migration via the control of the turnover of focal adhesion complexes. In this work we demonstrated that 17-estradiol (E2) regulates actin remodelling and cell movement in human umbilical vein endothelial cells (HUVEC) through the recruitment of FAK. E2 induces phosphorylation of FAK and its translocation towards membrane sites where focal adhesion complexes are assembled. This process is triggered via a G/G protein-dependent, rapid extra-nuclear signaling of estrogen receptor (ER) that interacts in a multiprotein complex with c-Src, phosphatidylinositol 3-OH kinase (PI3K) and FAK. Phosphorylation of FAK is fundamental for its activation, translocation to the plasmatic membrane and the subsequent formation of focal adhesion complexes. In conclusion, we found that ER enhances endothelial cell motility through the dynamic control of actin arrangement and the formation of focal adhesion complexes. The identification of these processes broadens the understanding of the actions of estrogens on endothelial cells and could be relevant in physiological or pathological settings.