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Review
. 2021 Apr 1;162(4):bqab016.
doi: 10.1210/endocr/bqab016.

Deiodinases and Cancer

Annarita Nappi  1 , Maria Angela De Stefano  1 , Monica Dentice  1 , Domenico Salvatore  2
Affiliations
Review

Deiodinases and Cancer

Annarita Nappi et al. Endocrinology. .

Abstract

Hormones are key drivers of cancer development, and alteration of the intratumoral concentration of thyroid hormone (TH) is a common feature of many human neoplasias. Besides the systemic control of TH levels, the expression and activity of deiodinases constitute a major mechanism for the cell-autonomous, prereceptoral control of TH action. The action of deiodinases ensures tight control of TH availability at intracellular level in a time- and tissue-specific manner, and alterations in deiodinase expression are frequent in tumors. Research over the past decades has shown that in cancer cells, a complex and dynamic expression of deiodinases is orchestrated by a network of growth factors, oncogenic proteins, and miRNA. It has become increasingly evident that this fine regulation exposes cancer cells to a dynamic concentration of TH that is functional to stimulate or inhibit various cellular functions. This review summarizes recent advances in the identification of the complex interplay between deiodinases and cancer and how this family of enzymes is relevant in cancer progression. We also discuss whether deiodinase expression could represent a diagnostic tool with which to define tumor staging in cancer treatment or even a therapeutic tool against cancer.

Keywords: cancer; deiodinase; proliferation; thyroid hormone action.

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Figures

Figure 1.
Figure 1.
The balance of deiodinase expression under normal conditions, in normal proliferative states and in cancer. Schematic illustration of D2 and D3 expression under various physiopathological conditions. The image shows the most common trend of Dio expression and how it is modified by various stimuli and in various contexts.
Figure 2.
Figure 2.
The deiodinase expression profile in cancer cell progression and the mechanism induced by thyroid hormone (TH) to promote the epithelial-to-mesenchymal transition (EMT). Illustration showing the progression of epithelial cancer toward a more aggressive stage and its correlation with an adaptive response of the intracellular TH concentration. The molecular mechanisms by which TH support the EMT are also depicted (right).
See this image and copyright information in PMC

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