| Autor: |
Miro, Caterina, Di Cicco, Emery, Ambrosio, Raffaele, Mancino, Giuseppina, Di Girolamo, Daniela, Cicatiello, Annunziata Gaetana, Sagliocchi, Serena, Nappi, Annarita, De Stefano, Maria Angela, Luongo, Cristina, Antonini, Dario, Visconte, Feliciano, Varricchio, Silvia, Ilardi, Gennaro, Del Vecchio, Luigi, Staibano, Stefania, Boelen, Anita, Blanpain, Cedric, Missero, Caterina, Salvatore, Domenico |
| Předmět: |
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| Zdroj: |
Nature Communications; 11/27/2019, Vol. 10 Issue 1, pN.PAG-N.PAG, 1p |
| Abstrakt: |
Epithelial tumor progression often involves epithelial-mesenchymal transition (EMT). We report that increased intracellular levels of thyroid hormone (TH) promote the EMT and malignant evolution of squamous cell carcinoma (SCC) cells. TH induces the EMT by transcriptionally up-regulating ZEB-1, mesenchymal genes and metalloproteases and suppresses E-cadherin expression. Accordingly, in human SCC, elevated D2 (the T3-producing enzyme) correlates with tumor grade and is associated with an increased risk of postsurgical relapse and shorter disease-free survival. These data provide the first in vivo demonstration that TH and its activating enzyme, D2, play an effective role not only in the EMT but also in the entire neoplastic cascade starting from tumor formation up to metastatic transformation, and supports the concept that TH is an EMT promoter. Our studies indicate that tumor progression relies on precise T3 availability, suggesting that pharmacological inactivation of D2 and TH signaling may suppress the metastatic proclivity of SCC. The invasion of epithelial tumours often depends on the epithelial-mesenchymal transition. Here, the authors report that intracellular activation of thyroid hormone by the D2 deiodinase enzyme promotes invasion and progression of squamous cell carcinoma by transcriptionally up-regulating ZEB-1. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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