Common Tumor Suppressive Signaling of Thyroid Hormone Receptor Beta in Breast and Thyroid Cancer Cells

The thyroid hormone receptor beta (TRß) 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 TRß abrogates tumorigenesis could aid in understanding the core tumor suppressive program that TRß facilitates. Here, we introduce TRß into the MDA-MB-468 basal-like breast cancer cell line and perform RNA-sequencing to determine changes in transcriptomic signaling. The TRß expressing MDA-MB-468 cells exhibit a more epithelial character as determined by PCA-PAM50 score and through repression of mesenchymal cytokeratins. The epithelial to mesenchymal transition pathway is also significantly reduced. The MDA-MB-468 dataset was also compared to RNA sequencing results from the thyroid cancer line SW1736 to determine which genes are TRß regulated across both tissue types. Stearate biosynthesis was revealed as upregulated from the shared gene set, a lipid which is known to repress breast tumorigenesis, as were chromatin remodeling pathways. These data provide novel insights into the molecular mechanisms by which TRß suppresses breast tumorigenesis and suggests a common metabolic role in breast and thyroid cancer as well a role for TRß in the maintenance of epithelial cellular identity. Overall design: Transcriptomic analysis of breast cancer cells that stably overexpress TRß and comparison with thyroid cancer cells that also overexpress TRß (GSE150364).