Abstract
Thyroid hormones play a critical role in the growth and development of the alimentary tract in vertebrates. Their effects are mediated by nuclear receptors as well as the cell surface receptor integrin αVβ3. Systemic thyroid hormone levels are controlled via activation and deactivation by iodothyronine deiodinases in the liver and other tissues. Given that thyroid hormone signaling has been characterized as a major effector of digestive system growth and homeostasis, numerous investigations have examined its role in the occurrence and progression of cancers in various tissues of this organ system. The present review summarizes current findings regarding the effects of thyroid hormone signaling on cancers of the esophagus, stomach, liver, pancreas, and colon. Particular attention is given to the roles of different thyroid hormone receptor isoforms, the novel integrin αVβ3 receptor, and thyroid hormone-related nutrients as possible protective agents and therapeutic targets. Future investigations geared towards a better understanding of thyroid hormone signaling in digestive system cancers may provide preventive or therapeutic strategies to diminish risk, improve outcome and avert recurrence in afflicted individuals.
Highlights
Follicular cells of the thyroid gland manufacture and secrete the thyroid hormones (THs)L-thyroxine, (T4) and L-triiodothyronine (T3)
Significant differences were found in the incidence of autoimmune thyroid disease between subjects with gastric cancer (GC) and control subjects, neither hyperthyroidism nor hypothyroidism was significantly associated with GC [47]
This study found no correlation between free T4 levels of serum and colorectal cancer (CRC), a negative association was found within CRC patients between serum thyroid-stimulating hormone (TSH) levels and serum carcinoembryonic antigen, the latter a tumor marker [99]
Summary
Follicular cells of the thyroid gland manufacture and secrete the thyroid hormones (THs). One site binds T3 to stimulate the PI3K pathway, leading to the translocation of TRα to the nucleus for transcription of HIF-1α; the other site binds primarily to T4 to activate ERK1/2 leading to nuclear localization of TRβ1 [17] The latter mechanism has been demonstrated to enhance mitogenesis and decrease apoptosis in tumor cells [18,19]. Given the important developmental and physiological functions of TH in the gut, a number of studies have examined the effects of TH on cancer prevention, development, and progression in various digestive tissues. Some of these relationships have been well characterized, while others remain poorly understood. This review focuses on the influence of TH signaling on multiple digestive system cancers with an emphasis on prevention and susceptibility
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