Role of estrogen on breast cancer cell movement via the activation Focal Adhesion Kinase

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

March 5-8, Venezia, Italy

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

Breast cancer is the major cause of cancer-related death in women and its treatment is particularly difficult when metastasis occurs. Cell migration, crucial for metastasis, is a highly integrated multistep process which regulates a large quantity of physiological conditions as repairing and regeneration of damaged tissues. The initial response of a cell to a migration-promoting agent is polarization and extension of membrane 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 a pivotal modulator of cell adhesion through the control of the assembly and turnover of Focal Adhesion complexes. FAK is a non-receptor tyrosine kinase that recruits Src family kinases and phosphatidyl-inositol-3 kinase (PI3K) via autophosphorylation. We used estrogen-progesteron receptor positive breast cancer cells and we sought to study estrogen action on FAK phosphorylation. Estrogen induces FAK phosphorylation in a dose-dependent manner with a peak of action after twenty 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. Our findings provide new data on estrogen action in breast cancer migration and metastasis highlighting new molecular mechanism by which estrogen exert this action.