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

Document Type: Research Articles

Authors

1 Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

2 Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

3 Department of Medical Genetics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

4 Stem Cell Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

5 Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

6 Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Abstract

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

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