Iodothyronine deiodinases and cancer

Thyroid hormones (TH) regulate key cellular processes, including proliferation, differentiation, and apoptosis in virtually all human cells. Disturbances in TH pathway and the resulting deregulation of these processes have been linked with neoplasia. The concentrations of TH in peripheral tissues are regulated via the activity of iodothyronine deiodinases. There are 3 types of these enzymes: type 1 and type 2 deiodinases are involved in TH activation while type 3 deiodinase inactivates TH. Expression and activity of iodothyronine deiodinases are disturbed in different types of neoplasia. According to the limited number of studies in cancer cell lines and mouse models changes in intratumoral and extratumoral T3 concentrations may influence proliferation rate and metastatic progression. Recent findings showing that increased expression of type 3 deiodinases may lead to enhanced tumoral proliferation support the idea that deiodinating enzymes have the potential to influence cancer progression. This review summarizes the observations of impaired expression and activity in different cancer types, published to date, and the mechanisms behind these alterations, including impaired regulation via TH receptors, transforming growth factor-β, and Sonic-hedgehog pathway. Possible roles of deiodinases as cancer markers and potential modulators of tumor progression are also discussed.