CONICET | Buscador de Institutos y Recursos Humanos

Breast cancer is the major cause of cancer-related death in women and its treatment is particularly difficult when metastasis occur. 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 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. These adhesion complexes are constituted of many molecules and they are tipically involved in cell cancer metastasis. Focal Adhesion Kinase (FAK) is a pivotal modulator of adhesion turnover. FAK is a non-receptor tyrosine kinase that recruits Src family kinases and phosphatidyl-inositol-3 kinase (PI3K) via autophosphorilation. The aim of the present study was to characterize the effects of 17beta-estradiol (E2) to FAK on T47-D breast cancer cell (ER+) cytoskeletal remodeling, migration and invasion. Our findings show that, estrogen induces FAK phosphorylation in a dose and time-dependent manner. 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. In the presence of physiological amounts of estradiol, E2 signal to FAK and displays a powerful effect on cell migration and invasion. Our findings provide new data on estrogen action via FAK in breast cancer migration and metastasis providing the molecular mechanism by which estrogen exert this action.

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