{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T21:35:37Z","timestamp":1782164137883,"version":"3.54.5"},"reference-count":73,"publisher":"The Endocrine Society","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,8,1]]},"abstract":"<jats:p>Dysregulation of the thyroid hormone receptor (TR)\u03b2 is common in human cancers. Restoration of functional TR\u03b2 delays tumor progression in models of thyroid and breast cancers implicating TR\u03b2 as a tumor suppressor. Conversely, aberrant expression of the runt-related transcription factor 2 (Runx2) is established in the progression and metastasis of thyroid, breast, and other cancers. Silencing of Runx2 diminishes tumor invasive characteristics. With TR\u03b2 as a tumor suppressor and Runx2 as a tumor promoter, a compelling question is whether there is a functional relationship between these regulatory factors in thyroid tumorigenesis. Here, we demonstrated that these proteins are reciprocally expressed in normal and malignant thyroid cells; TR\u03b2 is high in normal cells, and Runx2 is high in malignant cells. T3 induced a time- and concentration-dependent decrease in Runx2 expression. Silencing of TR\u03b2 by small interfering RNA knockdown resulted in a corresponding increase in Runx2 and Runx2-regulated genes, indicating that TR\u03b2 levels directly impact Runx2 expression and associated epithelial to mesenchymal transition molecules. TR\u03b2 specifically bound to 3 putative thyroid hormone-response element motifs within the Runx2-P1 promoter (\u2212105\/+133) as detected by EMSA and chromatin immunoprecipitation. TR\u03b2 suppressed Runx2 transcriptional activities, thus confirming TR\u03b2 regulation of Runx2 at functional thyroid hormone-response elements. Significantly, these findings indicate that a ratio of the tumor-suppressor TR\u03b2 and tumor-promoting Runx2 may reflect tumor aggression and serve as biomarkers in biopsy tissues. The discovery of this TR\u03b2-Runx2 signaling supports the emerging role of TR\u03b2 as a tumor suppressor and reveals a novel pathway for intervention.<\/jats:p>","DOI":"10.1210\/en.2015-2046","type":"journal-article","created":{"date-parts":[[2016,6,2]],"date-time":"2016-06-02T17:19:44Z","timestamp":1464887984000},"page":"3278-3292","source":"Crossref","is-referenced-by-count":28,"title":["Thyroid Hormone Receptor-\u03b2 (TR\u03b2) Mediates Runt-Related Transcription Factor 2 (Runx2) Expression in Thyroid Cancer Cells: A Novel Signaling Pathway in Thyroid Cancer"],"prefix":"10.1210","volume":"157","author":[{"given":"Frances E.","family":"Carr","sequence":"first","affiliation":[{"name":"Departments of Pharmacology (F.E.C., M.S.B., N.E.G., K.G.E., T.H.T., J.H.W., J.A.T.), College of Medicine, University of Vermont, Burlington, Vermont 05405"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip W. 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J.A.T.), College of Medicine, University of Vermont, Burlington, Vermont 05405"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas H.","family":"Taber","sequence":"first","affiliation":[{"name":"Departments of Pharmacology (F.E.C., M.S.B., N.E.G., K.G.E., T.H.T., J.H.W., J.A.T.), College of Medicine, University of Vermont, Burlington, Vermont 05405"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey H.","family":"White","sequence":"first","affiliation":[{"name":"Departments of Pharmacology (F.E.C., M.S.B., N.E.G., K.G.E., T.H.T., J.H.W., J.A.T.), College of Medicine, University of Vermont, Burlington, Vermont 05405"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer A.","family":"Tomczak","sequence":"first","affiliation":[{"name":"Departments of Pharmacology (F.E.C., M.S.B., N.E.G., K.G.E., T.H.T., J.H.W., J.A.T.), College of Medicine, University of Vermont, Burlington, Vermont 05405"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane M.","family":"Jaworski","sequence":"first","affiliation":[{"name":"DNeurological Sciences (D.M.J.), College of Medicine, University of Vermont, Burlington, Vermont 05405"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayyed K.","family":"Zaidi","sequence":"first","affiliation":[{"name":"DBiochemistry (P.W.L.T., S.K.Z., J.B.L., J.L.S., G.S.S.), College of Medicine, University of Vermont, Burlington, Vermont 05405"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane B.","family":"Lian","sequence":"first","affiliation":[{"name":"DBiochemistry (P.W.L.T., S.K.Z., J.B.L., J.L.S., G.S.S.), College of Medicine, University of Vermont, Burlington, Vermont 05405"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet L.","family":"Stein","sequence":"first","affiliation":[{"name":"DBiochemistry (P.W.L.T., S.K.Z., J.B.L., J.L.S., G.S.S.), College of Medicine, University of 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