Thyroid hormone induces progression and invasiveness of squamous cell carcinomas by promoting a ZEB-1/E-cadherin switch

Caterina Miro, Emery Di Cicco, Raffaele Ambrosio, Giuseppina Mancino, Daniela Di Girolamo, Annunziata Gaetana Cicatiello, Serena Sagliocchi, Annarita Nappi, Maria Angela De Stefano, Cristina Luongo, Dario Antonini, Feliciano Visconte, Silvia Varricchio, Gennaro Ilardi, Luigi Del Vecchio, Stefania Staibano, Anita Boelen, Cedric Blanpain, Caterina Missero, Domenico SalvatoreMonica Dentice

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number5410
JournalNature Communications
Volume10
Issue number1
DOIs
Publication statusPublished - Dec 1 2019

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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