Thyroid hormone receptor beta (TRβ) is a recognized tumor suppressor in numerous solid cancers. The molecular signaling of TRβ has been elucidated in several cancer types through re-expression models. Remarkably, the potential impact of selective activation of endogenous TRβ tumor progression remains largely unexplored. We used cell-based and in vivo assays to evaluate the effects of the TRβ agonist sobetirome (GC-1) on a particularly aggressive and dedifferentiated cancer, anaplastic thyroid cancer (ATC). Here we report that GC-1 reduced tumorigenic phenotypes, decreased cancer stem-like cell population, and increased the efficacy of current therapeutics. GC-1 induced re-differentiation of the ATC cells and increased sodium-iodide transporter (NIS) expression and restored iodide uptake. GC-1 alone was as effective as Sorafenib in blunting tumor growth in vivo. These results indicate that selective activation of TRβ not only induces a tumor suppression program de novo but enhances the effectiveness of anti-cancer agents.

中文翻译：

---

TRβ 激动剂在雌性小鼠中诱导肿瘤抑制并增强未变性甲状腺癌的药物疗效

甲状腺激素受体β (TRβ) 是多种实体癌中公认的肿瘤抑制因子。TRβ 的分子信号传导已通过重新表达模型在多种癌症类型中得到阐明。值得注意的是，选择性激活内源性 TRβ 肿瘤进展的潜在影响在很大程度上仍未得到探索。我们使用基于细胞的体内检测来评估 TRβ 激动剂 sobetirome (GC-1) 对一种特别具有侵袭性和去分化的癌症——未分化甲状腺癌 (ATC) 的作用。在此，我们报告 GC-1 减少了致瘤表型，减少了癌症干细胞样细胞群，并提高了当前治疗方法的疗效。GC-1 诱导 ATC 细胞的再分化，增加碘化钠转运蛋白 (NIS) 的表达并恢复碘化物的摄取。单独使用 GC-1 在抑制体内肿瘤生长方面与索拉非尼一样有效。这些结果表明，TRβ的选择性激活不仅可以从头诱导肿瘤抑制程序，而且可以增强抗癌药物的有效性。