TY - JOUR
T1 - Thyroid hormone induces progression and invasiveness of squamous cell carcinomas by promoting a ZEB-1/E-cadherin switch
AU - Miro, Caterina
AU - di Cicco, Emery
AU - Ambrosio, Raffaele
AU - Mancino, Giuseppina
AU - di Girolamo, Daniela
AU - Cicatiello, Annunziata Gaetana
AU - Sagliocchi, Serena
AU - Nappi, Annarita
AU - de Stefano, Maria Angela
AU - Luongo, Cristina
AU - Antonini, Dario
AU - Visconte, Feliciano
AU - Varricchio, Silvia
AU - Ilardi, Gennaro
AU - del Vecchio, Luigi
AU - Staibano, Stefania
AU - Boelen, Anita
AU - Blanpain, Cedric
AU - Missero, Caterina
AU - Salvatore, Domenico
AU - Dentice, Monica
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85075602075&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31776338
U2 - https://doi.org/10.1038/s41467-019-13140-2
DO - https://doi.org/10.1038/s41467-019-13140-2
M3 - Article
C2 - 31776338
SN - 2041-1723
VL - 10
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 5410
ER -