{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T15:30:49Z","timestamp":1781796649092,"version":"3.54.5"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,11]],"date-time":"2023-01-11T00:00:00Z","timestamp":1673395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Thyroid hormone as L-thyroxine (T4) acts nongenomically at physiological concentrations at its cancer cell surface receptor on integrin \u03b1v\u03b23 (\u2018thyrointegrin\u2019) to cause cancer cell proliferation. In the case of estrogen receptor (ER\u03b1)-positive breast cancer cells, T4 <jats:italic>via<\/jats:italic> the integrin promotes ER\u03b1-dependent cancer growth in the absence of estrogen. Thus, tumor growth in the post-menopausal patient with ER\u03b1-positive cancer may again be ER-dependent because of T4. Additional mechanisms by which T4 may contribute uniquely to aggressive breast cancer behavior\u2014independently of ER\u2014are 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 response is suboptimal to standard chemotherapy regimens. Euthyroidism in such a setting may be maintained with exogenous 3,3\u2019,5-triiodo-L-thyronine (T3).<\/jats:p>","DOI":"10.3389\/fendo.2022.1109555","type":"journal-article","created":{"date-parts":[[2023,1,11]],"date-time":"2023-01-11T05:25:17Z","timestamp":1673414717000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["(Thyroid) Hormonal regulation of breast cancer cells"],"prefix":"10.3389","volume":"13","author":[{"given":"Aleck","family":"Hercbergs","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung-Yun","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaker A.","family":"Mousa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Davis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2015.04.001","article-title":"Overlapping nongenomic and genomic actions of thyroid hormone and steroids","volume":"29","author":"Hammes","year":"2015","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1210\/er.2009-0007","article-title":"Molecular aspects of thyroid hormone actions","volume":"31","author":"Cheng","year":"2010","journal-title":"Endocr Rev"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.000328.2019","article-title":"Nongenomic actions of thyroid hormone: The interin component","volume":"101","author":"Davis","year":"2021","journal-title":"Physiol Rev"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1210\/en.2004-0308","article-title":"Thyroid hormone causes mitogen-activated protein kinase-dependent phosphorylation of the nuclear estrogen receptor","volume":"145","author":"Tang","year":"2004","journal-title":"Endocrinology"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.26143","article-title":"In tumor cells, thyroid hormone analogues non-immunologically regulate PD-L1 and PD-1 accumulation that is anti-apoptotic","volume":"9","author":"Lin","year":"2018","journal-title":"Oncotarget"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1210\/en.2005-0102","article-title":"Integrin alphavbeta3 contains a cell surface receptor site for thyroid hormone that is linked to activation of mitogen-activated protein kinase and induction of angiogenesis","volume":"146","author":"Bergh","year":"2005","journal-title":"Endocrinology"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s12672-018-0326-9","article-title":"Thyroid hormone in the clinic and breast cancer","volume":"9","author":"Hercbergs","year":"2018","journal-title":"Horm Cancer"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fpharm.2017.00561","article-title":"PD-1 and PD-L1 checkpoint signaling sinhibition for cancer immunotherapy: Mechanism, combinations, and clinical outcome","volume":"8","author":"Alsaab","year":"2017","journal-title":"Front Pharmacol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevvonc.2-17.06.001","article-title":"Biomarkers of response to PD-1\/PD-L1 inhibition","volume":"116","author":"Vareki","year":"2017","journal-title":"Crit Rev Oncol Hemtol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.cme.2021.111454","article-title":"Effects of thyroxine on apoptosis and proliferation of mammary tumors","volume":"538","author":"Zyla","year":"2021","journal-title":"Mol Cell Endocrinol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines6030089","article-title":"Contributions of thyroid hormone to cancer metastasis","volume":"6","author":"Mousa","year":"2018","journal-title":"Biomed"},{"key":"B12","doi-asserted-by":"publisher","first-page":"R20","DOI":"10.1186\/bcr1398","article-title":"Tumor-specific expression of \u03b1v\u03b23 integrin promotes spontaneous metastasis of breast cancer to bone","volume":"8","author":"Sloane","year":"2006","journal-title":"Breast Cancer Res"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1254\/jphs.14r01cr","article-title":"Mechanisms of p-glycoprotein alteration during anticancer treatment: Role of the pharmacokinetic and pharmacological effects of various substrate drugs","volume":"125","author":"Kabori","year":"2014","journal-title":"J Pharmacol Sci"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2012.02.024","article-title":"Increased expression of p-glycoprotein and doxorubicin chemoresistance of metastatic breast cancer is regulated by miR-298","volume":"180","author":"Bao","year":"2012","journal-title":"Am J Pathol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s1109-007-9495-x","article-title":"Thyroid hormone regulates the expression and function of p-glycoprotein in caco-2 cells","volume":"25","author":"Nishio","year":"2008","journal-title":"Pharm Res"},{"key":"B16","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.abb.2008.03.020","article-title":"Thyroid hormone receptor mediates human MDR1 gene expression \u2013 identification of the response region essential for gene expression","volume":"474","author":"Kurose","year":"2008","journal-title":"Arch Biochem Biophys"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-007-9088-7","article-title":"The impact of thyroid disease on the regulation, expression and function of ABCB1 (MDR1\/P-glycoprotein) and consequences of the disposition of digoxin","volume":"88","author":"Burk","year":"2010","journal-title":"Clin Pharmacol Ther"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2010.176","article-title":"Novel function of the thyroid hormone analogue tetraiodothyroacetic acid: A cancer chemosensitizing and anti-cancer agent","volume":"11","author":"Rebbaa","year":"2008","journal-title":"Angiogenesis"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-15-0989","article-title":"Hypothyroidism and hyperthyroidism and breast cancer risk: a nationwide cohort study","volume":"174","author":"Sogaard","year":"2016","journal-title":"Eur J Endocrinol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016-2104","article-title":"Thyroid function and cancer risk: The Rotterdam study","volume":"101","author":"Khan","year":"2016","journal-title":"J Clin Endocrinol Metab"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1007\/s00404-018-4837-y","article-title":"Levothyroxine use and the risk of breast cancer: A nation-wide population-based case-control study","volume":"298","author":"Wu","year":"2018","journal-title":"Arch Gynecol Obstet"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.20881","article-title":"Thyroid hormone and breast carcinoma. primary hypothyroidism is associated with a reduced incidence of primary breast cancer","volume":"103","author":"Cristofanilli","year":"2005","journal-title":"Cancer"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2014-0308","article-title":"Medically-induced euthyroid hypothyroxinemia may extend survival in compassionate need cancer patients: an observational study","volume":"20","author":"Hercbergs","year":"2015","journal-title":"Oncologist"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/168427","article-title":"Thyroid hormone and p-glycoprotein in tumor cells","volume":"2015","author":"Davis","year":"2015","journal-title":"BioMed Res Int"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2020.118761","article-title":"Expression of nuclear XIAP associated with cell growth and drug resistance and confers poor prognosis in breast cancer","volume":"1867","author":"Delbue","year":"2020","journal-title":"Biochim Biophys Acta (BBA) \u2013 Mol Cell Res"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.1109555\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,11]],"date-time":"2023-01-11T05:25:20Z","timestamp":1673414720000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.1109555\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,11]]},"references-count":25,"alternative-id":["10.3389\/fendo.2022.1109555"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2022.1109555","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,11]]},"article-number":"1109555"}}