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 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.

Targeting Phosphatases and Kinases: How to Checkmate Cancer

“…Accordingly, MEK inhibition induced the expression of pluripotency markers in thyroid cancer and melanoma cells (Dorris et al, 2016). On the other hand, targeting BRAF signaling pathway depleted the CD133 positive compartment in thyroid tumor (Bozorg-Ghalati et al, 2019) and synergized with cetuxiamb, an EGRF inhibitor, in reducing the CSC pool in colorectal cancer .…”

Promotion of cancer cell stemness by Ras

“…In this context, it may be interesting to understand, whether distinct oncogenic RAS alleles have a specific CSC promoting potential, given that they have different tumorigenicity [ 59 ]. A significant involvement of MAPK-signaling is furthermore supported by the fact that also BRAF-V600E promotes stemness traits [ 60 ], while MEK inhibitors broadly block stemness [ 9 , 24 , 56 ].…”