Di Cicco, Emery (2020) Thyroid hormone signaling in epithelial tumors: Role of type 2 deiodinase in the progression of Squamous cell Carcinoma. [Tesi di dottorato]


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Item Type: Tesi di dottorato
Lingua: English
Title: Thyroid hormone signaling in epithelial tumors: Role of type 2 deiodinase in the progression of Squamous cell Carcinoma
Di Cicco, Emeryemery.dicicco@unina.it
Date: 10 March 2020
Number of Pages: 45
Institution: Università degli Studi di Napoli Federico II
Department: Medicina Clinica e Chirurgia
Dottorato: Terapie avanzate medico-chirurgiche
Ciclo di dottorato: 32
Coordinatore del Corso di dottorato:
Di Minno, Giovannidiminno@unina.it
Dentice, MonicaUNSPECIFIED
Date: 10 March 2020
Number of Pages: 45
Uncontrolled Keywords: Thyroid hormone, skin cancer, deiodinases
Settori scientifico-disciplinari del MIUR: Area 05 - Scienze biologiche > BIO/09 - Fisiologia
Date Deposited: 22 Mar 2020 10:36
Last Modified: 10 Nov 2021 10:07
URI: http://www.fedoa.unina.it/id/eprint/13060


Epithelial tumorigenesis is a multistep process that promotes the progression from normal epithelial cells to clinically evident cancerous lesions capable of producing metastases. Cutaneous Squamous Cell Carcinoma (cSCC) is one of the most common cancer in humans that rarely metastasize, but metastasis is associated with a poor prognosis, with a low patient survival rate. Thyroid hormone (TH) plays a key role in the regulation of many biological processes including cell proliferation, differentiation and survival. In the target tissues, the concentration of TH is regulated by the actions of the deiodinases D2 and D3, which are viewed as a cell-specific pre-receptor mechanism to control thyroid hormone signaling that cannot be predicted based on the levels of circulating thyroid hormone. The association between dysregulation of TH signaling and human cancer was largely demonstrated. In the last years, our group provided the evidence of a functional link between the TH modulating enzymes, deiodinases, and non-melanoma skin cancer (NMSC) formation. In particular, we demonstrated that: i) D3 is overexpressed in basal cell carcinomas (BCCs) and is under the control of Hedgehog pathway; ii) TH treatment reduces tumor growth by attenuating the oncogenic potential of BCC tumor drivers Shh and miR21; iii) BCC cells express also D2 and the anti-tumorigenic action of TH in BCC can be attributed to its ability to reduce tumor cell proliferation, and increase the apoptotic rate. Although these evidences, the effective role of TH D2-produced in the progression of epithelial tumorigenesis was never been clarified. In this project, we described that intracellular activation of TH signaling by D2 enhances malignant evolution of SCCs, promoting epithelial-mesenchymal (EMT) transition of cancer cells. Accordingly, second tumors that expresses high level of D2, show aggressive phenotype and infiltration at distant sites. In human SCC, elevated D2 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 of the effective role of TH and its activating enzyme, D2, not only in the EMT, but also in the metastatic transformation and open new opportunities in the therapeutic field.


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