التفاصيل البيبلوغرافية
| العنوان: |
β-catenin attenuation leads to up-regulation of activating NKG2D ligands and tumor regression in BrafV600E-driven thyroid cancer cells. |
| المؤلفون: |
Minjing Zou, Al-Yahya, Suhad, Al-Alwan, Monther, BinEssa, Huda A., Khabar, Khalid S. A., Almohanna, Falah, Assiri, Abdullah M., Altaweel, Abdulmohsen, Qattan, Amal, Meyer, Brian F., Alzahrani, Ali S., Yufei Shi |
| المصدر: |
Frontiers in Immunology; 2023, p1-10, 10p |
| مصطلحات موضوعية: |
CANCER cells, LIGANDS (Biochemistry), CELL-mediated cytotoxicity, THYROID cancer, WNT signal transduction, TUMOR growth |
| مستخلص: |
Introduction: BRAFV600E mutations frequently occur in papillary thyroid cancer (PTC). β-catenin, encoded by CTNNB1, is a key downstream component of the canonical Wnt signaling pathway and is often overexpressed in PTC. BRAFV600Edriven PTC tumors rely onWnt/β-catenin signaling to sustain growth and progression. Methods: In the present study, we investigated the tumorigenicity of thyroid cancer cells derived from BRAFV600E PTCmice following Ctnnb1 ablation (BVE-Ctnnb1null). Results: Remarkably, the tumorigenic potential of BVE-Ctnnb1null tumor cells was lost in nude mice. Global gene expression analysis of BVE-Ctnnb1null tumor cells showed up-regulation of NKG2D receptor activating ligands (H60a, H60b, H60c, Raet1a, Raet1b, Raet1c, Raet1d, Raet1e, and Ulbp1) and down-regulation of inhibitory MHC class I molecules H-2L and H-2K2 in BVE-Ctnnb1null tumor cells. In vitro cytotoxicity assay demonstrated that BVE-Ctnnb1wt tumor cells were resistant to NK cell-mediated cytotoxicity, whereas BVE-Ctnnb1null tumor cells were sensitive to NK cell-mediated killing. Furthermore, the overexpression of any one of these NKG2D ligands in the BVE-Ctnnb1wt cell line resulted in a significant reduction of tumor growth in nude mice. Conclusions: Our results indicate that active β-catenin signaling inhibits NK cellmediated immune responses against thyroid cancer cells. Targeting the bcatenin signaling pathway may have significant therapeutic benefits for BRAFmutant thyroid cancer by not only inhibiting tumor growth but also enhancing host immune surveillance. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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