Evidence map›Paper›PMID 27253998›Full record

ArticleEndocrinology2016

Thyroid Hormone Receptor-β (TRβ) Mediates Runt-Related Transcription Factor 2 (Runx2) Expression in Thyroid Cancer Cells: A Novel Signaling Pathway in Thyroid Cancer.

Frances E Carr, Phillip W L Tai, Michael S Barnum, Noelle E Gillis, Katherine G Evans, Thomas H Taber, Jeffrey H White, Jennifer A Tomczak, Diane M Jaworski, Sayyed K Zaidi and 3 more

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Article in Endocrinology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.0field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. The emerging role of transcription factor FOXP3 in thyroid cancer.Reviews in endocrine & metabolic disorders · 2022
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 1 institution in 1 country.

Frances E CarrDepartments of Pharmacology (F.E.C., M.S.B., N.E.G., K.G.E., T.H.T., J.H.W., J.A.T.), Biochemistry (P.W.L.T., S.K.Z., J.B.L., J.L.S., G.S.S.), and Neurological Sciences (D.M.J.), College of Medicine, University of Vermont, Burlington, Vermont 05405.
Phillip W L TaiDepartments of Pharmacology (F.E.C., M.S.B., N.E.G., K.G.E., T.H.T., J.H.W., J.A.T.), Biochemistry (P.W.L.T., S.K.Z., J.B.L., J.L.S., G.S.S.), and Neurological Sciences (D.M.J.), College of Medicine, University of Vermont, Burlington, Vermont 05405.
Michael S BarnumDepartments of Pharmacology (F.E.C., M.S.B., N.E.G., K.G.E., T.H.T., J.H.W., J.A.T.), Biochemistry (P.W.L.T., S.K.Z., J.B.L., J.L.S., G.S.S.), and Neurological Sciences (D.M.J.), College of Medicine, University of Vermont, Burlington, Vermont 05405.
Noelle E GillisDepartments of Pharmacology (F.E.C., M.S.B., N.E.G., K.G.E., T.H.T., J.H.W., J.A.T.), Biochemistry (P.W.L.T., S.K.Z., J.B.L., J.L.S., G.S.S.), and Neurological Sciences (D.M.J.), College of Medicine, University of Vermont, Burlington, Vermont 05405.
Katherine G EvansDepartments of Pharmacology (F.E.C., M.S.B., N.E.G., K.G.E., T.H.T., J.H.W., J.A.T.), Biochemistry (P.W.L.T., S.K.Z., J.B.L., J.L.S., G.S.S.), and Neurological Sciences (D.M.J.), College of Medicine, University of Vermont, Burlington, Vermont 05405.
Thomas H TaberDepartments of Pharmacology (F.E.C., M.S.B., N.E.G., K.G.E., T.H.T., J.H.W., J.A.T.), Biochemistry (P.W.L.T., S.K.Z., J.B.L., J.L.S., G.S.S.), and Neurological Sciences (D.M.J.), College of Medicine, University of Vermont, Burlington, Vermont 05405.
Jeffrey H WhiteDepartments of Pharmacology (F.E.C., M.S.B., N.E.G., K.G.E., T.H.T., J.H.W., J.A.T.), Biochemistry (P.W.L.T., S.K.Z., J.B.L., J.L.S., G.S.S.), and Neurological Sciences (D.M.J.), College of Medicine, University of Vermont, Burlington, Vermont 05405.
Jennifer A TomczakDepartments of Pharmacology (F.E.C., M.S.B., N.E.G., K.G.E., T.H.T., J.H.W., J.A.T.), Biochemistry (P.W.L.T., S.K.Z., J.B.L., J.L.S., G.S.S.), and Neurological Sciences (D.M.J.), College of Medicine, University of Vermont, Burlington, Vermont 05405.
Diane M JaworskiDepartments of Pharmacology (F.E.C., M.S.B., N.E.G., K.G.E., T.H.T., J.H.W., J.A.T.), Biochemistry (P.W.L.T., S.K.Z., J.B.L., J.L.S., G.S.S.), and Neurological Sciences (D.M.J.), College of Medicine, University of Vermont, Burlington, Vermont 05405.
Sayyed K ZaidiDepartments of Pharmacology (F.E.C., M.S.B., N.E.G., K.G.E., T.H.T., J.H.W., J.A.T.), Biochemistry (P.W.L.T., S.K.Z., J.B.L., J.L.S., G.S.S.), and Neurological Sciences (D.M.J.), College of Medicine, University of Vermont, Burlington, Vermont 05405.
Jane B LianDepartments of Pharmacology (F.E.C., M.S.B., N.E.G., K.G.E., T.H.T., J.H.W., J.A.T.), Biochemistry (P.W.L.T., S.K.Z., J.B.L., J.L.S., G.S.S.), and Neurological Sciences (D.M.J.), College of Medicine, University of Vermont, Burlington, Vermont 05405.
Janet L SteinDepartments of Pharmacology (F.E.C., M.S.B., N.E.G., K.G.E., T.H.T., J.H.W., J.A.T.), Biochemistry (P.W.L.T., S.K.Z., J.B.L., J.L.S., G.S.S.), and Neurological Sciences (D.M.J.), College of Medicine, University of Vermont, Burlington, Vermont 05405.
Gary S SteinDepartments of Pharmacology (F.E.C., M.S.B., N.E.G., K.G.E., T.H.T., J.H.W., J.A.T.), Biochemistry (P.W.L.T., S.K.Z., J.B.L., J.L.S., G.S.S.), and Neurological Sciences (D.M.J.), College of Medicine, University of Vermont, Burlington, Vermont 05405.
University of Vermont · US

Funding

SUBNUCLEAR TARGETING OF TRANSCRIPTION FACTORSP01CA082834 · NCI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI STEIN, GARY S. · 2001 to 2015
$18.4M
CONTROL OF OSTEOBLAST PROLIFERATION AND DIFFERENTIATIONR01AR039588 · NIAMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LIAN, JANE B., STEIN, GARY S. · 1990 to 2019
$8.0M
Synthesis of Osteocalcin in BoneR37DE012528 · NIDCR · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LIAN, JANE B. · 2008 to 2017
$5.0M
NCI NIH HHS P01 CA082834NIAMS NIH HHS R01 AR039588NIDCR NIH HHS R37 DE012528
6 · The paper itself

Abstract

Dysregulation of the thyroid hormone receptor (TR)β is common in human cancers. Restoration of functional TRβ delays tumor progression in models of thyroid and breast cancers implicating TRβ 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 TRβ 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; TRβ 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 TRβ by small interfering RNA knockdown resulted in a corresponding increase in Runx2 and Runx2-regulated genes, indicating that TRβ levels directly impact Runx2 expression and associated epithelial to mesenchymal transition molecules. TRβ specifically bound to 3 putative thyroid hormone-response element motifs within the Runx2-P1 promoter ((-)105/(+)133) as detected by EMSA and chromatin immunoprecipitation. TRβ suppressed Runx2 transcriptional activities, thus confirming TRβ regulation of Runx2 at functional thyroid hormone-response elements. Significantly, these findings indicate that a ratio of the tumor-suppressor TRβ and tumor-promoting Runx2 may reflect tumor aggression and serve as biomarkers in biopsy tissues. The discovery of this TRβ-Runx2 signaling supports the emerging role of TRβ as a tumor suppressor and reveals a novel pathway for intervention.

Indexed as

CarcinogenesisCell Line, TumorCore Binding Factor Alpha 1 SubunitGene Expression Regulation, NeoplasticHumansPromoter Regions, GeneticResponse ElementsSignal TransductionThyroid GlandThyroid Hormone Receptors betaThyroid NeoplasmsTranscriptional ActivationTriiodothyronineCore Binding Factor Alpha 1 SubunitRUNX2 protein, humanThyroid Hormone Receptors betaTriiodothyronine

Identifiers

PMID27253998
PMCPMC4967127
OpenAlexW2412777376

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.