Thyroid hormones play important roles in regulating normal metabolism, development, and growth. They also stimulate
cancer cell proliferation. Their metabolic and developmental effects and growth effects in normal tissues are mediated primarily by
nuclear hormone receptors. A
cell surface receptor for the
hormone on
integrin [alpha]vβ3 is the initiation site for effects on
tumor cells. Clinical
hypothyroidism may retard
cancer growth, and
hyperthyroidism was recently linked to the prevalence of certain
cancers. Local levels of
thyroid hormones are controlled through activation and deactivation of iodothyronine deiodinases in different organs. The relative activities of different deiodinases that exist in tissues or organs also affect the progression and development of specific types of
cancers. In this review, the effects of
thyroid hormone on signaling pathways in breast, brain, liver, thyroid, and
colon cancers are discussed. The importance of nuclear
thyroid hormone receptor isoforms and of the
hormone receptor on the extracellular domain of
integrin [alpha]vβ3 as potential
cancer risk factors and therapeutic targets are addressed. We analyze the intracellular signaling pathways activated by
thyroid hormones in
cancer progression in
hyperthyroidism or at physiological concentrations in the euthyroid state. Determining how to utilize the deaminated
thyroid hormone analog (
tetrac), and its nanoparticulate derivative to reduce risks of
cancer progression, enhance therapeutic outcomes, and prevent
cancer recurrence is also deliberated. © 2016 American Physiological Society. Compr Physiol 6:1221-1237, 2016.