Evidence map›Paper›PMID 27435678›Full record

ArticleThe Journal of biological chemistry2016

Adipogenic Differentiation of Thyroid Cancer Cells Through the Pax8-PPARγ Fusion Protein Is Regulated by Thyroid Transcription Factor 1 (TTF-1).

Bin Xu, Michael O'Donnell, Jeffrey O'Donnell, Jingcheng Yu, Yanxiao Zhang, Maureen A Sartor, Ronald J Koenig

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
0.7field-weighted citation impact, top 26% 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

15 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. The Significance of PAX8-PPARContrast media & molecular imaging · 2022
    Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Adiponectin deficiency induces mitochondrial dysfunction and promotes endothelial activation and pulmonary vascular injury.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019
    Article
  14. Article
  15. Article
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

7 authors at 1 institution in 1 country.

Bin XuFrom the Department of Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes, University of Michigan Medical Center, Ann Arbor, Michigan 48109-5678 and bxu@umich.edu.
Michael O'DonnellFrom the Department of Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes, University of Michigan Medical Center, Ann Arbor, Michigan 48109-5678 and.
Jeffrey O'DonnellFrom the Department of Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes, University of Michigan Medical Center, Ann Arbor, Michigan 48109-5678 and.
Jingcheng YuFrom the Department of Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes, University of Michigan Medical Center, Ann Arbor, Michigan 48109-5678 and.
Yanxiao ZhangDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109-2218.
Maureen A SartorDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109-2218.
Ronald J KoenigFrom the Department of Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes, University of Michigan Medical Center, Ann Arbor, Michigan 48109-5678 and.
University of Michigan–Ann Arbor · US

Funding

Regional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Mehboob A Hussain · 2013 to 2026
$24.3M
In vivo therapy and mechanisms of PAX8-PPARgamma thyroid cancerR01CA166033 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KOENIG, RONALD JAY · 2013 to 2017
$2.4M
Pax8-PPARgamma regulation of transcription and metabolism in thyroid cancerR01CA151842 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KOENIG, RONALD JAY · 2010 to 2014
$1.6M
NCI NIH HHS R01 CA151842NCI NIH HHS R01 CA166033NIDDK NIH HHS P30 DK020572
6 · The paper itself

Abstract

A subset of thyroid carcinomas contains a t(2;3)(q13;p25) chromosomal translocation that fuses paired box gene 8 (PAX8) with the peroxisome proliferator-activated receptor γ gene (PPARG), resulting in expression of a PAX8-PPARγ fusion protein, PPFP. We previously generated a transgenic mouse model of PPFP thyroid carcinoma and showed that feeding the PPARγ agonist pioglitazone greatly decreased the size of the primary tumor and prevented metastatic disease in vivo The antitumor effect correlates with the fact that pioglitazone turns PPFP into a strongly PPARγ-like molecule, resulting in trans-differentiation of the thyroid cancer cells into adipocyte-like cells that lose malignant character as they become more differentiated. To further study this process, we performed cell culture experiments with thyrocytes from the PPFP mouse thyroid cancers. Our data show that pioglitazone induced cellular lipid accumulation and the expression of adipocyte marker genes in the cultured cells, and shRNA knockdown of PPFP eliminated this pioglitazone effect. In addition, we found that PPFP and thyroid transcription factor 1 (TTF-1) physically interact, and that these transcription factors bind near each other on numerous target genes. TTF-1 knockdown and overexpression studies showed that TTF-1 inhibits PPFP target gene expression and impairs adipogenic trans-differentiation. Surprisingly, pioglitazone repressed TTF-1 expression in PPFP-expressing thyrocytes. Our data indicate that TTF-1 interacts with PPFP to inhibit the pro-adipogenic response to pioglitazone, and that the ability of pioglitazone to decrease TTF-1 expression contributes to its pro-adipogenic action.

Indexed as

AdipogenesisCell DifferentiationAnimalsCell Line, TumorMiceNuclear ProteinsOncogene Proteins, FusionPAX8 Transcription FactorPPAR gammaRatsThyroid NeoplasmsThyroid Nuclear Factor 1Transcription FactorsNkx2-1 protein, mouseNkx2-1 protein, ratNuclear ProteinsOncogene Proteins, FusionPax8 protein, mousePax8 protein, ratPAX8 Transcription FactorPPAR gammaThyroid Nuclear Factor 1Transcription Factorscancerdifferentiationfusion proteingene expressionthyroid

Identifiers

PMID27435678
PMCPMC5016669
OpenAlexW2477731438

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.