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

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• 作者：Marina Inés Flamini ; Ivonne Denise Uzair ; Gisela Erika Pennacchio…
• 关键词：Triiodothyronine ; Src/FAK/PI3K ; Focal adhesion complex ; Breast cancer cell migration
• 刊名：Hormones and Cancer
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：8
• 期：1
• 页码：16-27
• 全文大小：
• 刊物主题：Oncology; Endocrinology; Cell Biology; Microbiology; Internal Medicine; Systems Biology;
• 出版者：Springer US
• ISSN：1868-8500
• 卷排序：8

文摘

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.