Miro, Caterina (2020) Thyroid hormone metabolism plays stage-specific roles in Squamous Cell Carcinoma (SCC) tumor progression. [Tesi di dottorato]

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Item Type: Tesi di dottorato
Lingua: English
Title: Thyroid hormone metabolism plays stage-specific roles in Squamous Cell Carcinoma (SCC) tumor progression.
Creators:
CreatorsEmail
Miro, Caterinacaterina.miro@unina.it
Date: 10 March 2020
Number of Pages: 64
Institution: Università degli Studi di Napoli Federico II
Department: Medicina Clinica e Chirurgia
Dottorato: Terapie avanzate biomediche e chirurgiche
Ciclo di dottorato: 32
Coordinatore del Corso di dottorato:
nomeemail
Di Minno, Giovannidiminno@unina.it
Tutor:
nomeemail
Salvatore, DomenicoUNSPECIFIED
Date: 10 March 2020
Number of Pages: 64
Uncontrolled Keywords: SKIN CANCER, THYROID HORMONE, DEIODINASES.
Settori scientifico-disciplinari del MIUR: Area 06 - Scienze mediche > MED/13 - Endocrinologia
Date Deposited: 22 Mar 2020 10:34
Last Modified: 10 Nov 2021 10:06
URI: http://www.fedoa.unina.it/id/eprint/13059

Abstract

Squamous cell carcinoma (SCC) is the second most frequent cancer worldwide and entails a substantial risk of metastasis. Thyroid hormone (TH) signalling regulates the metabolism, growth and differentiation of all cell types and tissues, and thus strongly impacts on cancer. However, our understanding of the effects exerted by TH on tumor formation and progression remains limited. Intracellular TH concentration is not simply the mirror of circulating TH levels but is regulated in the target tissues by a balance between the activating and inactivating deiodinases enzymes, D2 and D3 which provide the ability to fine-tune TH action at cell level. TH deregulation is frequent in human tumors, in particular type 3 iodothyronine deiodinase (D3), the thyroid hormone (TH)-inactivating enzyme, is overexpressed in hyper-proliferating contexts and in cancer. Studies from our group demonstrated that, by terminating TH action within the tumor microenvironment, D3 enhances cancer cell proliferation. The aim of my PhD thesis has been to understand how the TH regulation by the cell-specific action of its inactivating enzyme, D3, regulates multiple aspects of tumorigenesis, ranging from cancer formation to progression. Epithelial tumors arise through a multistep process in which invasion and metastasis often depend on the cancer cell epithelial-mesenchymal transition (EMT). We observed that the D3-mediated activation of the intracellular thyroid hormone (TH) signal promotes 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. Our study establishes a new role for TH in the tumorigenic process and describes a novel connection between a metabolic hormone and the invasive proclivity of SCC. Moreover, our data indicate that tumor progression depends on precise T3 availability and provide the rationale for the concept that pharmacological inactivation of TH signal reduces the progression and invasiveness of SCC, and probably of other hormone-sensitive carcinomas.

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