Estrogen and endometrial cells movement: possible role of focal adhesion kinase.

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

March 5-8, Venezia, Italy

Congreso; 13th World Congress on Human Reproduction.; 2009

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 occurs. The process of metastasis consists of sequential and selective steps including proliferation, motility, invasion, loss of cell-cell and cell-matrix adhesion, and remodelling of the extracellular matrix. A key factor involved in the control of cell-extracellular matrix interactions is focal adhesion kinase (FAK), an intracellular tyrosine kinase protein that is localised to cellular focal contact sites. Estrogens and progesterone can affect adhesion, migration, and invasion, mainly through inducing the remodeling of both the F-actin and the intermediate filament cell cytoskeletons. Thus, attempts to identify the molecular basis involved in metastasis are pivotal for the early prediction of endometrial cancer and development of novel molecular therapies. However, the identities of molecular alterations that endow cancer cells with these metastatic functions are largely unknown. We used endometrial cancer cells and human endometrial stromal cells to study estrogen action on FAK phosphorylation. 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.