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

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

doi:10.1038/s41467-023-36755-y

Cited by 15 publications

(9 citation statements)

References 64 publications

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“…During tumorigenesis, the cancer cells enable growth, angiogenesis, and metastasis through autocrine and paracrine signaling [35]. Recent research has shown that the loss of p53, which commonly occurs in SCC tumors, allows for increased expression of type 2 Deiodinase (D2), an enzyme that activates the thyroid hormone (TH) [36,37]. In turn, TH induces VEGF-A transcription in SCC tumor cells, fostering tumor angiogenesis, nutrient delivery, and cancer progression [38].…”

Section: Squamous Cell Carcinomamentioning

confidence: 99%

Review of the Tumor Microenvironment in Basal and Squamous Cell Carcinoma

Chiang

Stafford

Buell

et al. 2023

Cancers

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It is widely known that tumor cells of basal and squamous cell carcinoma interact with the cellular and acellular components of the tumor microenvironment to promote tumor growth and progression. While this environment differs for basal and squamous cell carcinoma, the cellular players within both create an immunosuppressed environment by downregulating effector CD4+ and CD8+ T cells and promoting the release of pro-oncogenic Th2 cytokines. Understanding the crosstalk that occurs within the tumor microenvironment has led to the development of immunotherapeutic agents, including vismodegib and cemiplimab to treat BCC and SCC, respectively. However, further investigation of the TME will provide the opportunity to discover novel treatment options.

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Section: Squamous Cell Carcinomamentioning

confidence: 99%

Review of the Tumor Microenvironment in Basal and Squamous Cell Carcinoma

Chiang

Stafford

Buell

et al. 2023

Cancers

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“…One of the many roles that p53 plays involves the intervention regarding the arrest and control of the cell cycle, apoptosis, DNA repair, senescence, or changes in metabolism. In the pathogenesis of cSCC, the inactivation of the p53 protein, which is caused by either genetic mutations or viral infections, such as HPV (human papilloma virus) infection, is implicated [16][17][18].…”

Section: Pathogenesis Of Csccmentioning

confidence: 99%

Pathophysiology, Histopathology, and Differential Diagnostics of Basal Cell Carcinoma and Cutaneous Squamous Cell Carcinoma—An Update from the Pathologist’s Point of View

Cocuz,

Popelea,

Niculescu

et al. 2024

IJMS

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Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) are the most frequently occurring non-melanocytic skin cancers. The objective of our study is to present the pathophysiology of BCC and cSCC and its direct relationship with the histopathological diagnostics and the differential diagnostics of these types of cancer, based on the morphological characteristics, immunohistochemical profile, and genetic alterations. The qualitative study was based on emphasizing the morphological characteristics and immunohistochemistry profiles of BCC and cSCC and the differential diagnostics based on the tissue samples from the Clinical Pathology Department of Mures Clinical County Hospital between 2020 and 2022. We analyzed the histopathological appearances and immunohistochemical profiles of BCC and cSCC in comparison with those of Bowen disease, keratoacanthoma, hyperkeratotic squamous papilloma, metatypical carcinoma, pilomatricoma, trichoblastoma, Merkel cell carcinoma, pleomorphic dermal sarcoma (PDS), and melanoma. Our study showed the importance of the correct histopathological diagnosis, which has a direct impact on the appropriate treatment and outcome for each patient. The study highlighted the histopathological and morphological characteristics of NMSCs and the precursor lesions in HE and the immunohistochemical profile for lesions that may make the differential diagnosis difficult to establish.

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“…Notably, THs are involved in the growth, invasion, and metastasis of cancer (35,36). Therefore, many studies have investigated the role of THs in PCa, but the results are controversial.…”

Section: Thyroid Hormones and Prostate Cancermentioning

confidence: 99%

The androgen-thyroid hormone crosstalk in prostate cancer and the clinical implications

Torabinejad

Miro

Barone

et al. 2023

European Thyroid Journal

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There is increasing evidence that thyroid hormones (THs) work in an integrative fashion with androgen receptors (ARs) to regulate gonadal differentiation and reproductive function. Studies reveal that THs have interactions with the AR promoter region and increase AR expression. THs also have a role in the regulation of enzymes involved in the biosynthesis of androgens, such as 5α-reductase, which is essential in the conversion of testosterone into its active form, 5α-dihydrotestosterone. Additionally, the presence of androgen response elements (AREs) in the promoter regions of TH-related genes, such as deiodinases and thyroid hormone receptor isoforms have been identified in some vertebrates, indicating a mutual interaction between THs and ARs. Since the androgen signaling pathway, mediated by ARs, plays a key role in the formation and progression of prostate cancer (PCa), the existence of crosstalk between THs and ARs supports the epidemiologic and experimental evidence indicating a relationship between the high incidence of Prostate Cancer (PCa) and hyperthyroidism. This article aims to review the role of androgen-thyroid hormone crosstalk in PCa and its implication in the clinical management. As life expectancy is growing these days, it can increase the number of patients with PCa and the critical relevance of the disease. In order to gain better knowledge about PCa and to improve the clinical management, it is essential to get better insight into the key factors related to the formation and progression of this cancer.

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

Cited by 15 publications

References 64 publications

Review of the Tumor Microenvironment in Basal and Squamous Cell Carcinoma

Review of the Tumor Microenvironment in Basal and Squamous Cell Carcinoma

Pathophysiology, Histopathology, and Differential Diagnostics of Basal Cell Carcinoma and Cutaneous Squamous Cell Carcinoma—An Update from the Pathologist’s Point of View

The androgen-thyroid hormone crosstalk in prostate cancer and the clinical implications

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