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 Salvatore and Monica Dentice ()
Additional contact information
Caterina Miro: University of Naples “Federico II”
Emery Di Cicco: University of Naples “Federico II”
Raffaele Ambrosio: IRCCS SDN
Giuseppina Mancino: University of Naples “Federico II”
Daniela Di Girolamo: University of Naples “Federico II”
Annunziata Gaetana Cicatiello: University of Naples “Federico II”
Serena Sagliocchi: University of Naples “Federico II”
Annarita Nappi: University of Naples “Federico II”
Maria Angela De Stefano: University of Naples “Federico II”
Cristina Luongo: University of Naples “Federico II”
Dario Antonini: University of Naples “Federico II”
Feliciano Visconte: CEINGE–Biotecnologie Avanzate Scarl
Silvia Varricchio: University of Naples “Federico II”
Gennaro Ilardi: University of Naples “Federico II”
Luigi Del Vecchio: CEINGE–Biotecnologie Avanzate Scarl
Stefania Staibano: University of Naples “Federico II”
Anita Boelen: Amsterdam University Medical Center, location AMC
Cedric Blanpain: IRIBHM, Université Libre de Bruxelles (ULB)
Caterina Missero: University of Naples “Federico II”
Domenico Salvatore: CEINGE–Biotecnologie Avanzate Scarl
Monica Dentice: University of Naples “Federico II”

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: 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.

Date: 2019
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-019-13140-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13140-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-13140-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().