Resumen
The Sodium/Iodide Simulator (NIS) is responsible for the uptake of iodide in the thyroid follicular cells. NIS is present in most differentiated thyroid carcinomas (DTC), allowing radioactive iodine (RAI) to be used to destroy malignant cells. However, a significant proportion of DTCs stop picking up iodide and become resistant to RAI therapy. This is mainly due to the symporter no longer being produced or not being placed correctly at the cell?s membrane. This has been associated with mechanisms linked to malignant transformation, namely the overactivation of the so-called MAPK pathway. Thus, several drugs have been developed to inhibit this pathway, attempting to increase NIS levels and iodide uptake. However, MAPK inhibitors have had only partial success in restoring NIS expression. We found that the activity of another protein, the small GTPase RAC1, has an important role in this process, determining the outcome of MAPK inhibitors. Thus, our findings open new opportunities to find effective therapeutic alternatives for DTC resistant to RAI.