甲状腺间变性癌
癌症研究
甲状腺癌
癌症
细胞生长
索拉非尼
癌症干细胞
癌细胞
生物
化学
内科学
医学
生物化学
肝细胞癌
作者
Noelle E. Gillis,Cole D Davidson,Cozzens Lm,Emma R. Wilson,Eric L. Bolf,Tomczak Ja,Carr Fe
标识
DOI:10.1101/2021.06.09.447689
摘要
ABSTRACT 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 on 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 the tumorigenic phenotype, decreased cancer stem-like cell populations, and induced re-differentiation of the ATC cell lines with different mutational backgrounds. Of note, this selective activation of TRβ amplified the effects of therapeutic agents in blunting the aggressive cell phenotype and stem-cell growth. In xenograft assays, GC-1 alone inhibited tumor growth and was as effective as the kinase inhibitor, Sorafenib. 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 revealing potential novel combination therapies for ATC and other aggressive solid tumors.
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