Mechanisms of regulating NIS transport to the cell membrane and redifferentiation therapy in thyroid cancer.

Iodine is an essential constituent of thyroid hormone. Active iodide accumulation in the thyroid is mediated by the sodium iodide symporter (NIS), comprising the first step in thyroid hormone biosynthesis, which relies on the functional expression of NIS on the cell membrane. The retention of NIS expressed in differentiated thyroid cancer (DTC) cells allows further treatment with post-operative radioactive iodine (RAI) therapy. However, compared with normal thyroid tissue, differentiated thyroid tumors usually show a decrease in the active iodide conveyance and NIS is generally retained within the cells, indicating that posttranslational protein transfer to the plasma membrane is abnormal. In recent years, through in vitro studies and studies of patients with DTC, various methods have been tested to increase the transport rate of NIS to the cell membrane and increase the absorption of iodine. An in-depth understanding of the mechanism of NIS transport to the plasma membrane could lead to improvements in RAI therapy. Therefore, in this review, we discuss the current knowledge concerning the post-translational mechanisms that regulate NIS transport to the cell membrane and the current status of redifferentiation therapy for patients with RAI-refractory (RAIR)-DTC.