Thyroid hormone regulates breast cancer cell movement via SRC/FAK/PI3K.

NEIRA FJ; UZAIR ID; JAHN GA; SANCHEZ AM

Potrero de los Funes

Congreso; XXX Reunión Científica Anual de la Sociedad de Biología de Cuyo; 2012

Sociedad de Biología de Cuyo

Thyroid hormones play a fundamental role in diverse process including cellular movement. Cell migration requires the integration of events that induce changes in cell structure towards the direction of migration. These actions are driven by actin remodelling and are stabilized by the development of adhesion sites to extracellular matrix via transmembrane receptors linked to the actin cytoskeleton. Focal Adhesion Kinase (FAK) is a non-receptor tyrosine kinase that facilitates cell migration and invasion via the control of the turnover of focal adhesion complexes. In this work we demonstrated that the thyroid hormone triiodothyronine (T3) regulates actin remodelling and cell movement on breast cancer cells (T47- D) through the recruitment of FAK. T3 control FAK phosphorylation and translocation at sites where focal adhesion complexes are assembled. This process is triggered via rapid signaling to c-Src, phosphatidylinositol 3-OH kinase (PI3K) and FAK. In addition, we used T47-D cells treated with T3 to induce a cellular model of hyperthyroidism and hypothyroidism. We found that in cellular hyperthyroidism model the expression of Src, FAK and PI3K remained constant respect to control, but in the hypothyroidism model Src, FAK and PI3K were significantly reduced. In conclusion, these results suggest a novel role for the thyroid hormone T3 as an important modulator of cellular migration, providing a starting point for the development of novel therapeutic strategies for the treatment of breast cancer.