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]
| 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 |
| Creators: |
| Creators | Email |
|---|
| Di Cicco, Emery | emery.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: |
| nome | email |
|---|
| Di Minno, Giovanni | diminno@unina.it |
|
| Tutor: |
| nome | email |
|---|
| Dentice, Monica | UNSPECIFIED |
|
| 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 |
[error in script]
[error in script]
| Date Deposited: |
22 Mar 2020 10:36 |
| Last Modified: |
10 Nov 2021 10:07 |
| URI: |
http://www.fedoa.unina.it/id/eprint/13060 |
Abstract
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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