Estrogen regulates endometrial cell cytoskeletal remodeling and motility via focal adhesion kinase.
OBJECTIVE
To explore the effects of 17β-estradiol (E(2)) on cytoskeletal remodeling and motility of endometrial stromal cells (ESC) and Ishikawa cells and to characterize the role of focal adhesion kinase (FAK) in these processes.


METHODS
In vitro study of cytoskeletal remodeling and cellular morphology and motility in ESC or Ishikawa cells.


METHODS
University research center.


METHODS
Endometrial samples obtained from women requiring endometrial biopsies.


METHODS
Treatments with E(2) and multiple inhibitors of signaling pathways.


METHODS
Activation of FAK, actin remodeling, membrane morphology, cell motility, and invasion.


RESULTS
Estrogen induces a rapid and concentration-related FAK phosphorylation in ESC and Ishikawa cells. In this time frame, FAK localizes to the plasma membrane at sites of focal adhesion complexes formation, as shown by immunofluorescence. Phosphorylation of FAK in the presence of estrogen depends on the recruitment of both estrogen receptor α and estrogen receptor β and of a rapid G protein-dependent signaling to c-Src and phosphatidylinositol 3-OH kinase. Activation of FAK in ESC and Ishikawa cells is required for estrogen-induced horizontal migration and invasion of three-dimensional matrices of endometrial cells.


CONCLUSIONS
Estrogen enhances cytoskeletal and membrane remodeling in ESC and Ishikawa cells by controlling FAK, thus resulting in enhanced cell motility and invasion. These findings may have clinical relevance for the development of new therapeutic strategies for the prevention or control of endometrial diseases.
Flamini
Marina Ines
MI
Molecular and Cellular Gynecological Endocrinology Laboratory, Department of Reproductive Medicine and Child Development, University of Pisa, Pisa, Italy.
Sanchez
Angel Matias
AM
Genazzani
Andrea Riccardo
AR
Simoncini
Tommaso
T
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D004717:Endometrium / Q000166:cytology / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D011960:Receptors, Estrogen / Q000819:agonists / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
D011960:Receptors, Estrogen; D004958:Estradiol; D051416:Focal Adhesion Protein-Tyrosine Kinases