Thyroid hormone suppresses medulloblastoma progression through promoting terminal differentiation of tumor cells.

in Cancer cell by 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

TLDR

  • The study found that thyroid hormone (TH) helps tumor cells in medulloblastoma (MB) become more like normal cells. This happens by freeing a protein called TRα1 to bind to another protein called EZH2, which then helps a protein called NeuroD1 do its job. When there's more TH, it helps TRα1 and EZH2 work together to make NeuroD1 do its job better, which makes the tumor cells become more like normal cells. This could help treat medulloblastoma.

Abstract

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.

Overview

  • The study investigates the role of thyroid hormone (TH) in promoting tumor cell differentiation in medulloblastoma (MB).
  • The methodology used includes reduction in TH levels and measurement of expression of NeuroD1, a transcription factor that drives tumor cell differentiation. Increased TH levels were also tested to determine if it reverses EZH2-mediated repression of NeuroD1 and stimulates tumor cell differentiation. Subject demographics were not specified in the abstract.

Comparative Analysis & Findings

  • 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 levels reverses EZH2-mediated repression of NeuroD1 by abrogating the binding of EZH2 and TRα1, thereby stimulating tumor cell differentiation and reducing MB growth. The study found that 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.

Implications and Future Directions

  • The findings establish an unprecedented association between TH signaling and MB pathogenicity, providing solid evidence for TH as a promising modality for MB treatment. Future research should focus on developing TH-based therapies for MB and further exploring the mechanisms underlying the interaction between TH and EZH2 in MB pathogenesis.
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