Estrogen signals to focal adhesion kinase facilitate endometrial cells movement.

M.I. FLAMINI; A.M. SANCHEZ; A.R. GENAZZANI; T. SIMONCINI

10-13 September, Rome, Italy

Congreso; 8th ESG Congress of the European Society of Gynecology.; 2009

European Society of Gynecology

Endometrial cancer is the fourth most diagnosed cancer in females. The majority of cases are in postmenopausal women and its treatment is particularly difficult when metastasis occur. Cell migration is a highly integrated multistep process which regulates a large quantity of physiological conditions. The initial response of a cell to a migration-promoting agent is polaring and extending protrusions 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 an important mediator of growth-factor signalling, cell proliferation, cell survival and cell migration. Given that the development of malignancy is often associated with perturbations in these processes, it is not surprising that FAK activity is altered in cancer cells. FAK is a pivotal modulator of adhesion turnover, it is a non-receptor tyrosine kinase that recruits Src family kinases and phosphatidyl-inositol-3 kinase via autophosphorilation. We used endometrial cancer cells and human endometrial stromal cells and we sought to study estrogen action on FAK phosphorilation. Estrogen induces FAK  phosphorylation in a dose-dependent manner with a peak of action after 10-15 minutes of exposure. Afterwards, FAK localizes to the plasma membrane with the formation of focal adhesion complexes that drive cells to move in the extracellular matrix and then to migrate. These findings increase our understanding of endometrial cancer cell biology and may have clinical relevance for the development of new therapeutic strategies for the prevention or control of endometrial cancer.