Thyroid Hormone Receptor Beta Suppresses Cancer Cell Activity by Differential Regulation of Glycogen Metabolism.

IF 3.3 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Endocrinology Pub Date : 2025-10-23 DOI:10.1210/endocr/bqaf156

Justin M Zielinski, Jennifer A Tomczak, Eyal Amiel, Frances E Carr

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引用次数: 0

Abstract

Anaplastic thyroid cancer (ATC) is one of the most lethal endocrine cancers with no enduring therapies. Thyroid hormone receptor beta (TRβ), a recognized tumor suppressor, modulates the transcriptome altering gene expression in numerous intracellular signaling pathways. Our recent studies revealed that TRβ agonism inhibits glycogen metabolism in ATC cells. Our goal in the present study was to delineate the molecular mechanisms by which TRβ regulates glycogen synthesis and breakdown. In ATC cells, activation of TRβ induced changes in expression of genes and proteins in glycogen signaling concordant with downregulation of cancer metabolism. The impact on the cancer cell metabolic phenotype was determined by glycogen levels, cell viability, and reactive oxygen species (ROS) characterization. Our results revealed that TRβ activation differentially regulates glycogen signaling pathways reflective of the genetic landscape of the cells. This suggests TRβ can suppress tumor growth and progression through multiple steps in glycogen metabolism, giving it a unique and distinct role in fine-tuning the microenvironment of the cell as an internal sensor of the general environment of the cell. These studies reveal the potential of synergistic impact of TRβ agonism and inhibition of glycogen metabolism in the treatment of aggressive dedifferentiated thyroid cancers.

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甲状腺激素受体β通过糖原代谢的差异调节抑制癌细胞活性。

间变性甲状腺癌（ATC）是最致命的内分泌肿瘤之一，没有持久的治疗方法。甲状腺激素受体β (TRβ)是一种公认的肿瘤抑制因子，在许多细胞内信号通路中调节转录组改变基因表达。我们最近的研究表明，TRβ激动作用抑制ATC细胞的糖原代谢。我们本研究的目的是描述TRβ调节糖原合成和分解的分子机制。在ATC细胞中，TRβ的激活引起糖原信号相关基因和蛋白的表达变化，与肿瘤代谢下调相一致。对癌细胞代谢表型的影响是通过糖原水平、细胞活力和活性氧（ROS）表征来确定的。我们的研究结果表明，TRβ活化对反映细胞遗传景观的糖原信号通路有差异调节。这表明TRβ可以通过糖原代谢的多个步骤抑制肿瘤的生长和进展，使其作为细胞一般环境的内部传感器在微调细胞微环境方面发挥独特而独特的作用。这些研究揭示了TRβ激动作用和糖原代谢抑制在治疗侵袭性去分化甲状腺癌中的潜在协同作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Endocrinology 医学-内分泌学与代谢

CiteScore

8.10

自引率

4.20%

发文量

195

审稿时长

2-3 weeks

期刊介绍： The mission of Endocrinology is to be the authoritative source of emerging hormone science and to disseminate that new knowledge to scientists, clinicians, and the public in a way that will enable "hormone science to health." Endocrinology welcomes the submission of original research investigating endocrine systems and diseases at all levels of biological organization, incorporating molecular mechanistic studies, such as hormone-receptor interactions, in all areas of endocrinology, as well as cross-disciplinary and integrative studies. The editors of Endocrinology encourage the submission of research in emerging areas not traditionally recognized as endocrinology or metabolism in addition to the following traditionally recognized fields: Adrenal; Bone Health and Osteoporosis; Cardiovascular Endocrinology; Diabetes; Endocrine-Disrupting Chemicals; Endocrine Neoplasia and Cancer; Growth; Neuroendocrinology; Nuclear Receptors and Their Ligands; Obesity; Reproductive Endocrinology; Signaling Pathways; and Thyroid.