Modulation of Sodium Iodide Symporter in Thyroid Cancer

Abstract

Radioactive iodine (RAI) is a key therapeutic modality for thyroid cancer. Loss of RAI uptake in thyroid cancer inversely correlates with patient’s survival. In this review, we focus on the challenges encountered in delivering sufficient doses of I-131 to eradicate metastatic lesions without increasing the risk of unwanted side effects. Sodium iodide symporter (NIS) mediates iodide influx, and NIS expression and function can be selectively enhanced in thyroid cells by thyroid-stimulating hormone. We summarize our current knowledge of NIS modulation in normal and cancer thyroid cells, and we propose that several reagents evaluated in clinical trials for other diseases can be used to restore or further increase RAI accumulation in thyroid cancer. Once validated in preclinical mouse models and clinical trials, these reagents, mostly small-molecule inhibitors, can be readily translated into clinical practice. We review available genetically engineered mouse models of thyroid cancer in terms of their tumor development and progression as well as their thyroid function. These mice will not only provide important insights into the mechanisms underlying the loss of RAI uptake in thyroid tumors but will also serve as preclinical animal models to evaluate the efficacy of candidate reagents to selectively increase RAI uptake in thyroid cancers. Taken together, we anticipate that the optimal use of RAI in the clinical management of thyroid cancer is yet to come in the near future.

Risk of Breast Cancer in Patients with Thyroid Cancer Receiving or Not Receiving 131I Treatment: A Nationwide Population-Based Cohort Study

“…The sodium-iodide symporter (NIS) is extremely relevant clinically, because it enables the treatment of thyroid cancer patients with radioiodine (11)(12)(13). The NIS is also found in the breasts, salivary lacrimal glands, gastric mucosa, and ovaries (14,15).…”

Effects of phytochemicals on thyroid function and their possible role in thyroid disease

“…Dedifferentiation may occur as a consequence of epithelial‐to‐mesenchymal transition, which is generally characterized by an increase in cell proliferation, migration, invasive properties, and resistance to cell death/apoptosis . Dedifferentiation is also associated with the downregulation or loss of expression of some markers related to thyrocyte differentiation, such as Tg and NIS …”

TNFα-mediated activation of NF-κB downregulates sodium-iodide symporter expression in thyroid cells

“…Despite TSHderived signaling being the key regulator of NIS expression in thyroid tissue, other signaling pathways may have an impact on this process. NIS expression levels and iodine uptake in DTC are reduced when compared to normal tissue [11,12] and this downregulation has been associated with the overactivation of several pathways linked to thyroid malignancy [13]. NF-κB signaling has been implicated in cancer-associated processes of several human malignancies, including thyroid cancer.…”