Molecular mechanisms underlying sodium iodide symporter expression at the plasma membrane in the thyroid follicular cell

Sodium iodide symporter (NIS)-mediated radioiodine accumulation in thyroid cancer cells is the cornerstone of radioiodine therapy for differentiated thyroid cancer. A recurring limitation of radioiodine therapy is the development of radioiodine-refractory metastatic thyroid cancer. Thyroid cancer cell dedifferentiation is the major cause of loss of radioiodine accumulation, resulting in a decreased NIS plasma membrane expression involving a plethora of transcriptional, post-transcriptional, and post-translational mechanisms. Immunohistochemical analysis revealed that most differentiated thyroid tumors preserve NIS protein expression, but NIS is often retained intracellularly, suggesting the presence of post-translational mechanisms that repress NIS plasma membrane expression. This review aims to discuss the current knowledge regarding the post-translational mechanisms that regulate NIS trafficking to the plasma membrane under physiological and pathological conditions. A thorough understanding of the molecular mechanisms underlying NIS expression at the plasma membrane would have multiple implications for radioiodine therapy, a pursuit that could uncover novel therapeutic interventions for radioiodine-refractory thyroid tumors.