title: Thyroid Hormone Controls Breast Cancer Cell Movement via Integrin αV/β3/SRC/FAK/PI3-Kinases.
abstract: Thyroid hormones (TH) play a fundamental role in diverse processes, 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 remodeling and 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 promotes cell migration and invasion through the control of focal adhesion turnover. In this work, we demonstrate that the thyroid hormone triiodothyronine (T3) regulates actin remodeling and cell movement in breast cancer T-47D cells through the recruitment of FAK. T3 controls FAK phosphorylation and translocation at sites where focal adhesion complexes are assembled. This process is triggered via rapid signaling to integrin αV/β3, Src, phosphatidylinositol 3-OH kinase (PI3K), and FAK. In addition, we established a cellular model with different concentration of T3 levels: normal, absence, and excess in T-47D breast cancer cells. We found that the expression of Src, FAK, and PI3K remained at normal levels in the excess of T3 model, while it was significantly reduced in the absence model. In conclusion, these results suggest a novel role for T3 as an important modulator of cell migration, providing a starting point for the development of new therapeutic strategies for breast cancer treatment.
authors.affiliation: Laboratorio de Biología Tumoral. Instituto de Medicina y Biología Experimental de Cuyo, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Mendoza, Argentina.
authors.forename: Marina Inés
authors.initials: MI
authors.lastname: Flamini
authors.affiliation: Laboratorio de Transducción de Señales y Movimiento Celular. Instituto de Medicina y Biología Experimental de Cuyo (IMBECU), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Av. Ruiz Leal s/n. Parque Gral. San Martin CC855, 5500, Mendoza, Argentina.
authors.forename: Ivonne Denise
authors.initials: ID
authors.lastname: Uzair
authors.affiliation: Laboratorio de Reproducción y Lactancia. Instituto de Medicina y Biología Experimental de Cuyo, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Mendoza, Argentina.
authors.forename: Gisela Erika
authors.initials: GE
authors.lastname: Pennacchio
authors.affiliation: Laboratorio de Transducción de Señales y Movimiento Celular. Instituto de Medicina y Biología Experimental de Cuyo (IMBECU), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Av. Ruiz Leal s/n. Parque Gral. San Martin CC855, 5500, Mendoza, Argentina.
authors.forename: Flavia Judith
authors.initials: FJ
authors.lastname: Neira
authors.affiliation: Laboratorio de Transducción de Señales y Movimiento Celular. Instituto de Medicina y Biología Experimental de Cuyo (IMBECU), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Av. Ruiz Leal s/n. Parque Gral. San Martin CC855, 5500, Mendoza, Argentina.
authors.forename: Joselina Magali
authors.initials: JM
authors.lastname: Mondaca
authors.affiliation: Laboratorio de Oncología. Instituto de Medicina y Biología Experimental de Cuyo, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Mendoza, Argentina.
authors.forename: Fernando Dario
authors.initials: FD
authors.lastname: Cuello-Carrión
authors.affiliation: Laboratorio de Reproducción y Lactancia. Instituto de Medicina y Biología Experimental de Cuyo, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Mendoza, Argentina.
authors.forename: Graciela Alma
authors.initials: GA
authors.lastname: Jahn
authors.affiliation: Molecular and Cellular Gynecological Endocrinology Laboratory (MCGEL), Department of Clinical and Experimental Medicine, University of Pisa, 56100, Pisa, Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Simoncini
authors.affiliation: Laboratorio de Transducción de Señales y Movimiento Celular. Instituto de Medicina y Biología Experimental de Cuyo (IMBECU), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Av. Ruiz Leal s/n. Parque Gral. San Martin CC855, 5500, Mendoza, Argentina. amsanchez@mendoza-conicet.gov.ar.
authors.forename: Angel Matías
authors.initials: AM
authors.lastname: Sanchez
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D022001:Focal Adhesions / Q000378:metabolism; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D021381:Protein Transport; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism; D015398:Signal Transduction; D014284:Triiodothyronine / Q000378:metabolism*
chemical_list: D039302:Integrin alphaVbeta3; D014284:Triiodothyronine; D019869:Phosphatidylinositol 3-Kinases; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D016392:Proto-Oncogene Proteins pp60(c-src)
keywords: Breast cancer cell migration; Focal adhesion complex; Src/FAK/PI3K; Triiodothyronine