: The Thyroid Hormone (TH) activating enzyme, type 2 Deiodinase (D2), is functionally required to elevate the TH concentration during cancer progression to advanced stages. However, the mechanisms regulating D2 expression in cancer still remain poorly understood. Here, we show that the cell stress sensor and tumor suppressor p53 silences D2 expression, thereby lowering the intracellular THs availability. Conversely, even partial loss of p53 elevates D2/TH resulting in stimulation and increased fitness of tumor cells by boosting a significant transcriptional program leading to modulation of genes involved in DNA damage and repair and redox signaling. In vivo genetic deletion of D2 significantly reduces cancer progression and suggests that targeting THs may represent a general tool reducing invasiveness in p53-mutated neoplasms.

Loss of p53 activates thyroid hormone via type 2 deiodinase and enhances DNA damage / Nappi, Annarita; Miro, Caterina; Pezone, Antonio; Tramontano, Alfonso; Di Cicco, Emery; Sagliocchi, Serena; Cicatiello, Annunziata Gaetana; Murolo, Melania; Torabinejad, Sepehr; Abbotto, Elena; Caiazzo, Giuseppina; Raia, Maddalena; Stornaiuolo, Mariano; Antonini, Dario; Fabbrocini, Gabriella; Salvatore, Domenico; Avvedimento, Vittorio Enrico; Dentice, Monica. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 14:1(2023), p. 1244. [10.1038/s41467-023-36755-y]

Loss of p53 activates thyroid hormone via type 2 deiodinase and enhances DNA damage

Nappi, Annarita;Miro, Caterina;Pezone, Antonio;Tramontano, Alfonso;Di Cicco, Emery;Sagliocchi, Serena;Cicatiello, Annunziata Gaetana;Murolo, Melania;Torabinejad, Sepehr;Caiazzo, Giuseppina;Raia, Maddalena;Stornaiuolo, Mariano;Antonini, Dario;Fabbrocini, Gabriella;Salvatore, Domenico;Avvedimento, Vittorio Enrico;Dentice, Monica
2023

Abstract

: The Thyroid Hormone (TH) activating enzyme, type 2 Deiodinase (D2), is functionally required to elevate the TH concentration during cancer progression to advanced stages. However, the mechanisms regulating D2 expression in cancer still remain poorly understood. Here, we show that the cell stress sensor and tumor suppressor p53 silences D2 expression, thereby lowering the intracellular THs availability. Conversely, even partial loss of p53 elevates D2/TH resulting in stimulation and increased fitness of tumor cells by boosting a significant transcriptional program leading to modulation of genes involved in DNA damage and repair and redox signaling. In vivo genetic deletion of D2 significantly reduces cancer progression and suggests that targeting THs may represent a general tool reducing invasiveness in p53-mutated neoplasms.
2023
Loss of p53 activates thyroid hormone via type 2 deiodinase and enhances DNA damage / Nappi, Annarita; Miro, Caterina; Pezone, Antonio; Tramontano, Alfonso; Di Cicco, Emery; Sagliocchi, Serena; Cicatiello, Annunziata Gaetana; Murolo, Melania; Torabinejad, Sepehr; Abbotto, Elena; Caiazzo, Giuseppina; Raia, Maddalena; Stornaiuolo, Mariano; Antonini, Dario; Fabbrocini, Gabriella; Salvatore, Domenico; Avvedimento, Vittorio Enrico; Dentice, Monica. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 14:1(2023), p. 1244. [10.1038/s41467-023-36755-y]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/914093
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