ArticleProceedings of the National Academy of Sciences of the United States of America2018
Noncanonical agonist PPARγ ligands modulate the response to DNA damage and sensitize cancer cells to cytotoxic chemotherapy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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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.
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Who cites it
30 citing papers in PubMed, 56 citations in OpenAlex.
- PPARγ acetylation governs mammary adenocarcinoma tumor growth via acetylated residues that determine DNA sequence-specific binding.Oncogene · 2025Article
- PPAR-γ in Melanoma and Immune Cells: Insights into Disease Pathogenesis and Therapeutic Implications.Cells · 2025Review
- Emerging connectivity of programmed cell death pathways and pulmonary vascular remodelling during pulmonary hypertension.Journal of cellular and molecular medicine · 2024Review
- Pioglitazone enhances cisplatin's impact on triple-negative breast cancer: Role of PPARγ in cell apoptosis.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2024Article
- Dual function of activated PPARγ by ligands on tumor growth and immunotherapy.Medical oncology (Northwood, London, England) · 2024Review
- Hydroxy-Safflower Yellow A Mitigates Vascular Remodeling in Rat Pulmonary Arterial Hypertension.Drug design, development and therapy · 2024Article
- Microtubule Dynamics Deregulation Induces Apoptosis in Human Urothelial Bladder Cancer Cells via a p53-Independent Pathway.Cancers · 2023Article
- Dynamic SUMOylation of MORC2 orchestrates chromatin remodelling and DNA repair in response to DNA damage and drives chemoresistance in breast cancer.Theranostics · 2023Article
- Monounsaturated and Diunsaturated Fatty Acids Sensitize Cervical Cancer to Radiation Therapy.Cancer research · 2022Article
- Review
- Transcription factors in the pathogenesis of pulmonary arterial hypertension-Current knowledge and therapeutic potential.Frontiers in cardiovascular medicine · 2022Review
- Stage-stratified molecular profiling of non-muscle-invasive bladder cancer enhances biological, clinical, and therapeutic insight.Cell reports. Medicine · 2021Article
- Adipose MDM2 regulates systemic insulin sensitivity.Scientific reports · 2021Article
- Hepatocarcinogenesis Prevention by Pirfenidone Is PPARγ Mediated and Involves Modification of Nuclear NF-kB p65/p50 Ratio.International journal of molecular sciences · 2021Article
- Epigenetic derepression converts PPARγ into a druggable target in triple-negative and endocrine-resistant breast cancers.Cell death discovery · 2021Article
- Mutations of p53 associated with pancreatic cancer and therapeutic implications.Annals of hepato-biliary-pancreatic surgery · 2021Review
- CRTC1/MAML2 directs a PGC-1α-IGF-1 circuit that confers vulnerability to PPARγ inhibition.Cell reports · 2021Article
- PPARγ-p53-Mediated Vasculoregenerative Program to Reverse Pulmonary Hypertension.Circulation research · 2021Article
- A Randomized Phase II Trial Comparing the Efficacy and Safety of Pioglitazone, Clarithromycin and Metronomic Low-Dose Chemotherapy with Single-Agent Nivolumab Therapy in Patients with Advanced Non-small Cell Lung Cancer Treated in Second or Further Line (ModuLung).Frontiers in pharmacology · 2021Article
- PPARgamma in Metabolism, Immunity, and Cancer: Unified and Diverse Mechanisms of Action.Frontiers in endocrinology · 2021Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
The peroxisome-proliferator receptor-γ (PPARγ) is expressed in multiple cancer types. Recently, our group has shown that PPARγ is phosphorylated on serine 273 (S273), which selectively modulates the transcriptional program controlled by this protein. PPARγ ligands, including thiazolidinediones (TZDs), block S273 phosphorylation. This activity is chemically separable from the canonical activation of the receptor by agonist ligands and, importantly, these noncanonical agonist ligands do not cause some of the known side effects of TZDs. Here, we show that phosphorylation of S273 of PPARγ occurs in cancer cells on exposure to DNA damaging agents. Blocking this phosphorylation genetically or pharmacologically increases accumulation of DNA damage, resulting in apoptotic cell death. A genetic signature of PPARγ phosphorylation is associated with worse outcomes in response to chemotherapy in human patients. Noncanonical agonist ligands sensitize lung cancer xenografts and genetically induced lung tumors to carboplatin therapy. Moreover, inhibition of this phosphorylation results in deregulation of p53 signaling, and biochemical studies show that PPARγ physically interacts with p53 in a manner dependent on S273 phosphorylation. These data implicate a role for PPARγ in modifying the p53 response to cytotoxic therapy, which can be modulated for therapeutic gain using these compounds.
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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.