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Increased expression of NKG2D ligands in BrafV600E-driven thyroid cancer cells with β-catenin ablation

ABSTRACT: BRAFV600E mutation frequently occurs in papillary thyroid cancer (PTC). β-catenin, encoded by CTNNB1, is a key downstream component of canonical Wnt signaling pathway and is often overexpressed in PTC. BRAFV600E-driven PTC tumors rely on Wnt/β-catenin signaling to sustain their growth and progression. In the present study, we investigated the tumorigenicity of thyroid cancer cells derived from BrafV600E PTC mice after Ctnnb1 ablation (BVE-Ctnnb1null). Remarkably, the tumorigenic potential of BVE-Ctnnb1null tumor cells was lost in nude mice. RNA-Seq analysis of the 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 the 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, overexpression of any one of these NKG2D ligands in the BVE-Ctnnb1wt cell line resulted in significant reduction of tumor growth in nude mice. Our results indicate that active β-catenin signaling inhibits NK cell-mediated immune response against thyroid cancer cells. Targeting β-catenin signaling pathway may have significant therapeutic benefit for thyroid cancer by not only inhibiting tumor growth but also enhancing host immune surveillance.

ORGANISM(S): Mus musculus

PROVIDER: GSE207695 | GEO | 2023/02/09

REPOSITORIES: GEO

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Increased expression of NKG2D ligands in BrafV600E-driven thyroid cancer cells with β-catenin ablation

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