间叶型甲状腺癌（ATC）是人类最具侵略性的实体癌之一，治疗选择有限。近期的研究表明，肿瘤干细胞（CSC）活性导致了ATC治疗抵抗和复发。我们展示了内源性甲状腺激素受体β基因（THRB）在ATC中被沉默，并且表明外源性表达的TRβ能够抑制CSC活性。脱甲基化剂Decitabine是治疗骨髓增生异常综合征和急性髓系早幼细胞白血病患者的一种方法，并且目前正在用于临床试验中的造血恶性疾患和实体瘤。我们的目标是利用Decitabine重新激活内源性THRB基因的表达，减弱CSC活性以阻止ATC肿瘤生长。我们将来自人类ATC肿瘤（11T和16T细胞）的细胞系用Decitabine进行处理，并在体内外异种移植模型中评估重新激活的内源性TRβ对CSC活性的影响。我们发现，Decitabine处理11T和16T细胞可以重新激活内源性TRβ的表达，这可以通过Western blot和免疫组织化学分析得到证实。表达的TRβ通过阻止细胞的S期停滞来抑制细胞增殖，通过上调剪切的Caspase-3促进细胞凋亡，而且显著抑制CSC的调节因子表达，包括cMYC，ALDH，SOX2，CD44和β-catenin。 Decitabine通过压制CSC活性，抑制癌细胞增殖和促进细胞凋亡，从而抑制异种移植肿瘤的生长。我们的发现表明，通过抑制CSC活性重新表达内源性TRβ是一种新的针对ATC的治疗方法。

Anaplastic thyroid cancer (ATC) is one of the most aggressive solid cancers in humans, with limited treatment options. Recent studies suggest that cancer stem cell (CSC) activity contributes to therapeutic resistance and recurrence of ATC. We show that the expression of the endogenous thyroid hormone receptor β gene (THRB) is silenced in ATC and demonstrate that the exogenously expressed TRβ suppresses CSC activity. Decitabine is one of the demethylation agents to treat myelodysplastic syndrome and acute myeloid leukemia patients and currently in clinical trials for hematopoietic malignancies and solid tumors. We aim to show that the re-expression of the endogenous THRB gene by decitabine can attenuate CSC activity to block ATC tumor growth. We treated ATC cell lines derived from human ATC tumors (11T and 16T cells) with decitabine and evaluated the effects of the reactivated endogenous TRβ on CSC activity in vitro and in vivo xenograft models. We found that treatment of 11T and 16T cells with decitabine reactivated the expression of endogenous TRβ, as evidenced by western blot and immunohistochemical analyses. The expressed TRβ inhibited cell proliferation by arresting cells at the S phase, increased apoptotic cell death by upregulation of cleaved caspase-3, and markedly suppressed the expression of CSC regulators, including cMYC, ALDH, SOX2, CD44 and β-catenin. Decitabine also inhibited xenograft tumor growth by suppressing CSC activity, inhibiting cancer cell proliferation and increasing apoptosis. Our findings suggest that re-expression of the endogenous TRβ is a novel therapeutic approach for ATC via suppression of CSC activity.