甲状腺激素通过促进肿瘤细胞的终末分化来抑制髓母细胞瘤的进展。
Thyroid hormone suppresses medulloblastoma progression through promoting terminal differentiation of tumor cells.
发表日期：2024 Aug 12
作者：
Yijun Yang, Silvia Anahi Valdés-Rives, Qing Liu, Tong Gao, Chakkapong Burudpakdee, Yuzhe Li, Jun Tan, Yinfei Tan, Christian A Koch, Yuan Rong, Steven R Houser, Shuanzeng Wei, Kathy Q Cai, Jinhua Wu, Sheue-Yann Cheng, Robert Wechsler-Reya, Zeng-Jie Yang
来源：
CANCER CELL
摘要：
甲状腺功能减退症常见于髓母细胞瘤 (MB) 患者。然而，甲状腺激素 (TH) 是否会导致 MB 致病性仍不清楚。在这里，我们发现 TH 在促进肿瘤细胞分化中发挥着关键作用。 TH 水平的降低会释放 TH 受体 TRα1，使其与 EZH2 结合并抑制 NeuroD1（一种驱动肿瘤细胞分化的转录因子）的表达。 TH 增加通过消除 EZH2 和 TRα1 的结合来逆转 EZH2 介导的 NeuroD1 抑制，从而刺激肿瘤细胞分化并减少 MB 生长。重要的是，TH 诱导的肿瘤细胞分化不受 MB 分子亚型的限制，这表明 TH 可用于广泛治疗 MB 亚型。这些发现在 TH 信号传导与 MB 致病性之间建立了前所未有的关联，为 TH 作为一种有前途的 MB 治疗方式提供了坚实的证据。版权所有 © 2024 Elsevier Inc. 保留所有权利。
Hypothyroidism is commonly detected in patients with medulloblastoma (MB). However, whether thyroid hormone (TH) contributes to MB pathogenicity remains undetermined. Here, we find that TH plays a critical role in promoting tumor cell differentiation. Reduction in TH levels frees the TH receptor, TRα1, to bind to EZH2 and repress expression of NeuroD1, a transcription factor that drives tumor cell differentiation. Increased TH reverses EZH2-mediated repression of NeuroD1 by abrogating the binding of EZH2 and TRα1, thereby stimulating tumor cell differentiation and reducing MB growth. Importantly, TH-induced differentiation of tumor cells is not restricted by the molecular subgroup of MB, suggesting that TH can be used to broadly treat MB subgroups. These findings establish an unprecedented association between TH signaling and MB pathogenicity, providing solid evidence for TH as a promising modality for MB treatment.Copyright © 2024 Elsevier Inc. All rights reserved.