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

Author

Listed:
  • 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”
    CEINGE–Biotecnologie Avanzate Scarl)

  • Domenico Salvatore

    (CEINGE–Biotecnologie Avanzate Scarl
    University of Naples “Federico II”)

  • Monica Dentice

    (University of Naples “Federico II”
    CEINGE–Biotecnologie Avanzate Scarl)

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.

Suggested Citation

  • Caterina Miro & Emery Di Cicco & Raffaele Ambrosio & Giuseppina Mancino & Daniela Di Girolamo & Annunziata Gaetana Cicatiello & Serena Sagliocchi & Annarita Nappi & Maria Angela De Stefano & Cristina , 2019. "Thyroid hormone induces progression and invasiveness of squamous cell carcinomas by promoting a ZEB-1/E-cadherin switch," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13140-2
    DOI: 10.1038/s41467-019-13140-2
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    Cited by:

    1. Annarita Nappi & Caterina Miro & Antonio Pezone & Alfonso Tramontano & Emery Cicco & Serena Sagliocchi & Annunziata Gaetana Cicatiello & Melania Murolo & Sepehr Torabinejad & Elena Abbotto & Giuseppin, 2023. "Loss of p53 activates thyroid hormone via type 2 deiodinase and enhances DNA damage," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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