Thyroid Hormone Controls Breast Cancer Cell Movement via Integrin αV/β3/SRC/FAK/PI3-Kinases

FLAMINI MI; UZAIR ID; PENNACCHIO GE; NEIRA FJ; MONDACA JM; CUELLO CARRION FD; JAHN GA; SIMONCINI T; SANCHEZ AM

Hormones and cancer

SPRINGER

Lugar: New York; Año: 2017 vol. 8 p. 16 - 27

1868-8497

Thyroid hormones (TH) play a fundamental role indiverse processes, including cellular movement. Cell migrationrequires the integration of events that induce changes incell structure towards the direction of migration. These actionsare driven by actin remodeling and stabilized by the developmentof adhesion sites to extracellular matrix via transmembranereceptors linked to the actin cytoskeleton. Focal adhesionkinase (FAK) is a non-receptor tyrosine kinase that promotescell migration and invasion through the control of focaladhesion turnover. In this work, we demonstrate that the thyroidhormone triiodothyronine (T3) regulates actinremodeling and cell movement in breast cancer T-47D cellsthrough the recruitment of FAK. T3 controls FAK phosphorylationand translocation at sites where focal adhesion complexesare assembled. This process is triggered via rapid signalingto integrin αV/β3, Src, phosphatidylinositol 3-OH kinase(PI3K), and FAK. In addition, we established a cellularmodel with different concentration of T3 levels: normal, absence,and excess in T-47D breast cancer cells.We found thatthe expression of Src, FAK, and PI3K remained at normallevels in the excess of T3 model, while it was significantlyreduced in the absence model. In conclusion, these resultssuggest a novel role for T3 as an important modulator of cellmigration, providing a starting point for the development ofnew therapeutic strategies for breast cancer treatment.