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).
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.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- A per- and polyfluoroalkyl substances-based gene signature links prognosis to immune landscapes in thyroid cancer.Translational cancer research · 2026Article
- Potential Molecular Associations Between Triphenyl Phosphate Exposure and Thyroid Cancer: Integration of Network Toxicology and Machine Learning for Core Target Identification with Molecular Docking.International journal of molecular sciences · 2026Article
- In Silico Search for Drug Candidates Targeting the PAX8-PPARγ Fusion Protein in Thyroid Cancer.International journal of molecular sciences · 2024Article
- A Critical Role for IFN-β Signaling for IFN-κ Induction in Keratinocytes.Frontiers in lupus · 2024Article
- Acetylated-PPARγ expression is regulated by differentCancer biology & medicine · 2023Article
- Drug repositioning in thyroid cancer treatment: the intriguing case of anti-diabetic drugs.Frontiers in pharmacology · 2023Review
- CD44-positive cancer stem cells from oral squamous cell carcinoma exhibit reduced proliferation and stemness gene expression upon adipogenic induction.Medical oncology (Northwood, London, England) · 2022Article
- The Significance of PAX8-PPARContrast media & molecular imaging · 2022Article
- In silico modeling of PAX8-PPARγ fusion protein in thyroid carcinoma: influence of structural perturbation by fusion on ligand-binding affinity.Journal of computer-aided molecular design · 2021Article
- Epigenetic Regulators of White Adipocyte Browning.Epigenomes · 2021Review
- Differential Effects of Estrogen Receptor Alpha and Beta on Endogenous Ligands of Peroxisome Proliferator-Activated Receptor Gamma in Papillary Thyroid Cancer.Frontiers in endocrinology · 2021Article
- Novel role of ASH1L histone methyltransferase in anaplastic thyroid carcinoma.The Journal of biological chemistry · 2020Article
- 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 · 2019Article
- The transcription factor NKX1-2 promotes adipogenesis and may contribute to a balance between adipocyte and osteoblast differentiation.The Journal of biological chemistry · 2019Article
- SULT1E1 inhibits cell proliferation and invasion by activating PPARγ in breast cancer.Journal of Cancer · 2018Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
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.
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Registered trials
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.