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Novel Approach to Restoring Sodium-Iodide Symporter Expression in Anaplastic Thyroid Cancer

By: Kelly M. Hennessey, PhD
Posted: Tuesday, January 12, 2021

Anaplastic thyroid carcinoma is a rare thyroid tumor lacking the typical differentiation features common to other types of thyroid cancer. Defects in sodium-iodide symporter (NIS) expression, structure, or translocation seem to limit the ability of anaplastic thyroid carcinoma tissue to concentrate iodine, limiting the efficacy of the frequently used radioactive iodine regimen. Vahid Haghpanah, MD, MPH, PhD, of Tehran University of Medical Sciences, Iran, and colleagues created a protein interaction network to better understand NIS expression regulation. Their results were published in Scientific Reports.

The network consisted of 167 input proteins, including four signaling pathways and transcription factors that regulate NIS expression. The analysis included both centrality and modularity. Centrality analysis utilized eight indices to rank proteins; high-ranking proteins indicated protein essentiality within the network. They found no correlation between the frequency of mutations and any of the centrality indices after comparing the rate of mutations of the 167 protein-coding genes with the essentiality of the proteins in the network.

Information-flow and distance-based centrality indices were used to predict proteins required to regulate NIS expression; these categories were emphasized when averaging ranks. Proteins frequently mutated in anaplastic thyroid cancers ranked near the top and included AKT1, TP53, PIK3CA, PIK3CB, MAPK3, PIK3CD, PIK3CG, SRC, MAPK1, and MYC, all of which are main proteins of AKT/PI3K or MAPK pathway.

In patients with anaplastic thyroid carcinoma, a combination therapy approach to induce NIS expression was suggested if the targets are essential proteins. “Several genes/proteins in the NIS expression regulatory network are interesting targets for manipulation, including AKT1, TP53, PIK3C, MAPK1, MAPK3, SRC, MYC, EGR1, XIAP, BCL2L1, CASP3, and CASP9,” they proposed. “However, NIS downregulation is not the only abnormality that results in an ability of thyroid cells to uptake iodide, and that NIS translocation is also worth considering,” they acknowledged.   

Disclosure: The study authors reported no conflicts of interest.

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