Focal adhesion kinase and endometrial cancer cells movement: possible role of estrogen and progesterone.

M.I. FLAMINI; A.M. SANCHEZ; X. FU; M.S. GIRETTI; L. GOGLIA; S. GARIBALDI; C. BALDACCI; V. TOSI; L. GABRIELE; A.R. GENAZZANI; T. SIMONCINI

February 28-March 2, Florence, Italy

Congreso; 13th World Congress of Gynecological Endocrinology.; 2008

Endometrial cancer is the fourth most diagnosed cancer in females. The majority of cases are in postmenopausal women and its treatment is particularly difficult  then metastasis occurs. 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 the development of polarization and the extension of protrusions toward 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. 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 autophosphorylation. We used endometrial cancer cells and we sought to study estrogen and progesterone action on FAK phosphorylation. Estrogen and progesterone induce 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.