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

Mol Carcinog. 2021 Dec;60(12):874-885. doi: 10.1002/mc.23352. Epub 2021 Sep 17.

Abstract

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. The TRβ expressing MDA-MB-468 cells exhibit a more epithelial character as determined by principle component analysis-based iterative PAM50 subtyping score and through reduced expression of mesenchymal cytokeratins. The epithelial to mesenchymal transition pathway is also significantly reduced. The MDA-MB-468 data set was further compared with RNA sequencing results from TRβ expressing thyroid cancer cell line SW1736 to determine which genes are TRβ correspondingly regulated across both cell types. Several pathways including lipid metabolism and chromatin remodeling processes were observed to be altered in the shared gene set. These data provide novel insights into the molecular mechanisms by which TRβ suppresses breast tumorigenesis.

Keywords: breast cancer; gene expression; thyroid cancer; thyroid hormone.