TRβ Agonism Induces Tumor Suppression and Enhances Drug Efficacy in Anaplastic Thyroid Cancer in Female Mice.

Thyroid hormone receptor beta (TRβ) is a recognized tumor suppressor in numerous solid cancers. The molecular signaling of TRβ has been elucidated in several cancer types through re-expression models. Remarkably, the potential impact of selective activation of endogenous TRβ on tumor progression remains largely unexplored.

Common tumor-suppressive signaling of thyroid hormone receptor beta in breast and thyroid cancer cells.

The thyroid hormone receptor beta (TRβ) is a tumor suppressor in multiple types of solid tumors, most prominently in breast and thyroid cancer. An increased understanding of the molecular mechanisms by which TRβ abrogates tumorigenesis will aid in understanding the core tumor-suppressive functions of TRβ. Here, we restored TRβ expression in the MDA-MB-468 basal-like breast cancer cell line and perform RNA-sequencing to determine the TRβ-mediated changes in gene expression and associated signaling pathways.

Thyroid Hormone Receptor Beta Inhibits PI3K-Akt-mTOR Signaling Axis in Anaplastic Thyroid Cancer via Genomic Mechanisms.

Thyroid cancer is the most common endocrine malignancy, and the global incidence has increased rapidly over the past few decades. Anaplastic thyroid cancer (ATC) is highly aggressive, dedifferentiated, and patients have a median survival of fewer than 6 months. Oncogenic alterations in ATC include aberrant phosphoinositide 3 kinase (PI3K) signaling through receptor tyrosine kinase (RTK) amplification, loss of phosphoinositide phosphatase expression and function, and protein kinase B (Akt) amplification.

Thyroid Hormone Receptor Beta Induces a Tumor-Suppressive Program in Anaplastic Thyroid Cancer.

The thyroid hormone receptor beta (TRβ), a key regulator of cellular growth and differentiation, is frequently dysregulated in cancers. Diminished expression of TRβ is noted in thyroid, breast, and other solid tumors and is correlated with more aggressive disease. Restoration of TRβ levels decreased tumor growth supporting the concept that TRβ could function as a tumor suppressor.