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

Justin M Zielinski1,2, Jennifer A Tomczak2,3, Eyal Amiel4

  • 1Department of Biochemistry, Larner College of Medicine, University of Vermont, Burlington, VT 05405, USA.

Endocrinology
|October 23, 2025
PubMed

Insights

Thyroid hormone receptor β (TRβ) activation suppresses anaplastic thyroid cancer (ATC) growth by regulating glycogen metabolism. This finding suggests a potential synergistic therapy combining TRβ agonism with glycogen metabolism inhibition for aggressive thyroid cancers.

Area of Science:

  • Endocrinology
  • Cancer Biology
  • Molecular Metabolism

Background:

  • Anaplastic thyroid cancer (ATC) is a highly lethal endocrine malignancy with limited therapeutic options.
  • Thyroid hormone receptor β (TRβ) acts as a tumor suppressor, influencing gene expression and cellular pathways.
  • Previous research indicated TRβ agonism inhibits glycogen metabolism in ATC cells.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying TRβ's regulation of glycogen synthesis and breakdown in ATC.
  • To investigate how TRβ activation impacts the metabolic phenotype of ATC cells.

Main Methods:

  • Activation of TRβ in ATC cells.
  • Analysis of gene and protein expression in glycogen signaling pathways.
  • Assessment of cellular glycogen levels, viability, and reactive oxygen species (ROS).

Main Results:

  • TRβ activation led to altered expression of genes and proteins involved in glycogen signaling.
  • These changes correlated with a downregulation of cancer cell metabolism.
  • TRβ activation differentially regulated glycogen signaling pathways based on the cells' genetic makeup.

Conclusions:

  • TRβ suppresses tumor growth and progression by modulating multiple steps in glycogen metabolism.
  • TRβ plays a distinct role in fine-tuning the cellular microenvironment.
  • TRβ agonism combined with glycogen metabolism inhibition shows potential as a synergistic treatment for aggressive thyroid cancers.
Keywords:
ROScancerglycogenmetabolismsignaling

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