ArticleMolecular cancer therapeutics2010
Peroxisome proliferator-activated receptor-gamma activation inhibits tumor metastasis by antagonizing Smad3-mediated epithelial-mesenchymal transition.
Article in Molecular cancer therapeutics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 136 citations in OpenAlex.
- Epithelial to mesenchymal transition and M2 macrophages drive aggressiveness in murine and human sarcomatoid urothelial carcinoma.bioRxiv : the preprint server for biology · 2026Article
- E2A selectively regulates TGF-β-induced apoptosis in KRAS-mutant non-small cell lung cancer.Molecular oncology · 2026Article
- Pioglitazone-Based Combination Approaches for Non-Small-Cell Lung Cancer.Pharmaceutics · 2025Review
- Review
- 12/15-lipoxygenase orchestrates murine wound healing via PPARγ-activating oxylipins acting holistically to dampen inflammation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Non-small cell lung cancer map and analysis: exploring interconnected oncogenic signal integrators.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Article
- Specific Deletions of Chromosomes 3p, 5q, 13q, and 21q among Patients with G2 Grade of Non-Small Cell Lung Cancer.International journal of molecular sciences · 2024Article
- PPARγ Modulators in Lung Cancer: Molecular Mechanisms, Clinical Prospects, and Challenges.Biomolecules · 2024Review
- The epithelial-mesenchymal plasticity landscape: principles of design and mechanisms of regulation.Nature reviews. Genetics · 2023Review
- Transcriptomics Based Network Analyses and Molecular Docking Highlighted Potentially Therapeutic Biomarkers for Colon Cancer.Biochemical genetics · 2023Article
- Article
- The role of peroxisome proliferator-activated receptors in the tumor microenvironment, tumor cell metabolism, and anticancer therapy.Frontiers in pharmacology · 2023Review
- Role of the epithelial barrier in intestinal fibrosis associated with inflammatory bowel disease: relevance of the epithelial-to mesenchymal transition.Frontiers in cell and developmental biology · 2023Review
- Review
- Targeting Nuclear Receptors in Lung Cancer-Novel Therapeutic Prospects.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Renal Cell Cancer and Obesity.International journal of molecular sciences · 2022Review
- Mechanical Strain Induces Transcriptomic Reprogramming of Saphenous Vein Progenitors.Frontiers in cardiovascular medicine · 2022Article
- Lobeglitazone, A Peroxisome Proliferator-Activated Receptor-Gamma Agonist, Inhibits Papillary Thyroid Cancer Cell Migration and Invasion by Suppressing p38 MAPK Signaling Pathway.Endocrinology and metabolism (Seoul, Korea) · 2021Article
- Enhancer RNA lnc-CES1-1 inhibits decidual cell migration by interacting with RNA-binding protein FUS and activating PPARγ in URPL.Molecular therapy. Nucleic acids · 2021Article
- Exploring natural killer cell immunology as a therapeutic strategy in lung cancer.Translational lung cancer research · 2021Review
28 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Epithelial-mesenchymal transition (EMT) was shown to confer tumor cells with abilities essential for metastasis, including migratory phenotype, invasiveness, resistance to apoptosis, evading immune surveillance, and tumor stem cell traits. Therefore, inhibition of EMT can be an important therapeutic strategy to inhibit tumor metastasis. Here, we show that activation of peroxisome proliferator-activated receptor γ (PPAR-γ) inhibits transforming growth factor β (TGF-β)-induced EMT in lung cancer cells and prevents metastasis by antagonizing Smad3 function. Activation of PPAR-γ by synthetic ligands (troglitazone and rosiglitazone) or by a constitutively active form of PPAR-γ prevents TGF-β-induced loss of E-cadherin expression and inhibits the induction of mesenchymal markers (vimentin, N-cadherin, fibronectin) and matrix metalloproteases. Consistently, activation of PPAR-γ also inhibited EMT-induced migration and invasion of lung cancer cells. Furthermore, effects of PPAR-γ ligands were attenuated by siRNA-mediated knockdown of PPAR-γ, indicating that the ligand-induced responses are PPAR-γ dependent. Selective knockdown of Smad2 and Smad3 by siRNA showed that TGF-β-induced EMT is Smad3 dependent in lung cancer cells. Activation of PPAR-γ inhibits TGF-β-induced Smad transcriptional activity but had no effect on the phosphorylation or nuclear translocation of Smads. Consistently, PPAR-γ activation prevented TGF-β-induced transcriptional repression of E-cadherin promoter and inhibited transcriptional activation of N-cadherin promoter. Finally, treatment of mice with troglitazone or knockdown of Smad3 in tumor cells significantly inhibited TGF-β-induced experimental metastasis in SCID-Beige mice. Together, with the low toxicity profile of PPAR-γ ligands, our data show that these ligands may serve as potential therapeutic agents to inhibit metastasis.
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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.