Estrogen regulates endometrial cell cytoskeletal remodeling and motility via focal adhesion kinase

Abstract

Objective: To explore the effects of 17β-estradiol (E2) 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. Design: In vitro study of cytoskeletal remodeling and cellular morphology and motility in ESC or Ishikawa cells. Setting: University research center. Patient(s): Endometrial samples obtained from women requiring endometrial biopsies. Intervention(s): Treatments with E2 and multiple inhibitors of signaling pathways. Main Outcome Measure(s): Activation of FAK, actin remodeling, membrane morphology, cell motility, and invasion. Result(s): 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. Conclusion(s): 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.