Targeting the BRAF Signaling Pathway in CD133pos Cancer Stem Cells of Anaplastic Thyroid Carcinoma

Abstract

Background: Cancer stem cells (CSCs) with a self-renewal ability in tumor cells population, execute a pivotal<br />function in tumorigenesis, retrogression, and metastasis of malignant cancers such as anaplastic thyroid carcinoma<br />(ATC). Materials and Methods: In this study, we isolated CSCs subpopulation with CD133 surface marker from<br />three ATC cell lines by magnetic cell sorting assay. After confirming the segregation by the flow cytometry method,<br />BRAF and sodium-iodide symporter (NIS) genes were investigated in them before and after incubation with BRAF<br />inhibitor. Also, we evaluated the NIS protein expression and localization. Results: Established upon q-RT PCR data,<br />when compared to human normal thyrocytes, the BRAFV600E gene was over-expressed in CD133pos cells (>1705.99 ±<br />55.55 fold, Mean ± SEM, n=3, P- value<0.05), whilst the expression of NIS gene was very restricted (< 0.0008 ± 5.43<br />fold, Mean ± SEM, n=3, P- value<0.05) in them. Also, our results showed that BRAF inhibition affected NIS protein<br />expression and localization. Conclusions: Current study showed that the differentiate genes/proteins expression can<br />be induced in the CSCs via focus on signal transduction pathways and targeting their molecules, that are involved in<br />expression of these genes/proteins. Therefore, attention to targeting CSCs along with routine thyroid cancer therapy,<br />can help to ATC treatment.