AUTHOR=Hercbergs Aleck , Lin Hung-Yun , Mousa Shaker A. , Davis Paul J. 

TITLE=(Thyroid) Hormonal regulation of breast cancer cells

JOURNAL=Frontiers in Endocrinology

VOLUME=Volume 13 - 2022

YEAR=2023

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.1109555

DOI=10.3389/fendo.2022.1109555

ISSN=1664-2392

ABSTRACT=Thyroid hormone as L-thyroxine (T4) acts nongenomically in physiological concentrations at its cancer cell surface receptor on integrin alphavbeta3 ('thyrointegrin') to cause cell proliferation.  In the case of estrogen receptor (ERalpha)-positive breast cancer cells, T4 via the integrin promotes ERalpha-dependent cancer growth in the absence of estrogen.  Thus, tumor growth in the post-menopausal patient with ERalpha-positive cancer may again be ER-dependent because of T4.  Additional mechanisms by which T4 may contribute uniquely to aggressive breast cancer behavior--independently of ER--are stimulation of immune checkpoint inhibitor gene expression and of several anti-apoptosis mechanisms.  These observations may call for consideration of elimination of host T4 production in breast cancer patients whose responses to standard chemotherapy are suboptimal.  Euthyroidism in such a setting may be maintained with exogenous 3,3',5-triiodo-L-thyronine (T3).