Estrogen receptor-{alpha} promotes endothelial cell motility through focal adhesion kinase.
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 such as protrusion, polarization and traction toward the direction of migration. These actions are driven by actin remodeling 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 17β-estradiol (E(2)) regulates actin remodeling and cell movement in human umbilical vein endothelial cells through the recruitment of FAK. E(2) induces phosphorylation of FAK and its translocation toward membrane sites where focal adhesion complexes are assembled. This process is triggered via a Gα/Gβ protein-dependent, rapid extra-nuclear signaling of estrogen receptor-α (ERα) that interacts in a multiprotein complex with c-Src, phosphatidylinositol 3-OH kinase 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 ERα 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.
Molecular and Cellular Gynecological Endocrinology Laboratory (MCGEL), Department of Reproductive Medicine and Child Development, Division of Obstetrics and Gynecology, University of Pisa, Via Roma, 57, Pisa 56100, Italy.
Angel Matias
AM
Sanchez
Marina Ines
MI
Flamini
Sara
S
Zullino
Santhosh
S
Gopal
Andrea Riccardo
AR
Genazzani
Tommaso
T
Simoncini
D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D015398:Signal Transduction; D014471:Umbilical Veins / Q000378:metabolism; D015854:Up-Regulation
C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D004967:Estrogens; D051416:Focal Adhesion Protein-Tyrosine Kinases