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Thyroid Hormone Receptor Beta as Tumor Suppressor: Untapped Potential in Treatment and Diagnostics in Solid Tumors
Cole D Davidson1,2, Noelle E Gillis1,2, Frances E Carr1,2
1Department of Pharmacology, Larner College of Medicine, University of Vermont, Burlington, VT 05405, USA.
Abstract:
There is compelling evidence that the nuclear receptor TRβ, a member of the thyroid hormone receptor (TR) family, is a tumor suppressor in thyroid, breast, and other solid tumors. Cell-based and animal studies reveal that the liganded TRβ induces apoptosis, reduces an aggressive phenotype, decreases stem cell populations, and slows tumor growth through modulation of a complex interplay of transcriptional networks. TRβ-driven tumor suppressive transcriptomic signatures include repression of known drivers of proliferation such as PI3K/Akt pathway, activation of novel signaling such as JAK1/STAT1, and metabolic reprogramming in both thyroid and breast cancers. The presence of TRβ is also correlated with a positive prognosis and response to therapeutics in BRCA+ and triple-negative breast cancers, respectively. Ligand activation of TRβ enhances sensitivity to chemotherapeutics. TRβ co-regulators and bromodomain-containing chromatin remodeling proteins are emergent therapeutic targets. This review considers TRβ as a potential biomolecular diagnostic and therapeutic target.
Insights
The thyroid hormone receptor beta (TRβ) acts as a tumor suppressor by inducing apoptosis and slowing tumor growth. Activating TRβ may enhance cancer therapy effectiveness and offers a potential diagnostic and therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Endocrinology
Background:
- The nuclear receptor TRβ, part of the thyroid hormone receptor (TR) family, shows evidence of tumor suppressor activity in various solid tumors.
- TRβ's role in modulating complex transcriptional networks is crucial for its anti-tumorigenic effects.
Purpose of the Study:
- To review the evidence supporting TRβ's function as a tumor suppressor.
- To explore TRβ's mechanisms of action in cancer, including its impact on signaling pathways and cellular processes.
- To discuss TRβ as a potential diagnostic and therapeutic target in oncology.
Main Methods:
- Review of cell-based and animal studies investigating TRβ function.
- Analysis of TRβ-driven transcriptomic signatures in cancer.
- Correlation of TRβ expression with patient prognosis and therapeutic response.
Main Results:
- Liganded TRβ induces apoptosis, reduces tumor aggressiveness, and decreases stem cell populations.
- TRβ modulates proliferation pathways (e.g., repressing PI3K/Akt) and activates novel signaling (e.g., JAK1/STAT1).
- TRβ presence correlates with better prognosis in BRCA+ cancers and enhanced sensitivity to chemotherapy in triple-negative breast cancer.
Conclusions:
- TRβ is a significant tumor suppressor with broad implications in thyroid, breast, and other solid tumors.
- TRβ activation enhances anti-cancer effects and improves therapeutic sensitivity.
- TRβ and associated co-regulators represent promising targets for cancer diagnostics and therapeutics.
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