ArticleThe Journal of biological chemistry2016
Nuclear Factor of Activated T Cells-dependent Down-regulation of the Transcription Factor Glioma-associated Protein 1 (GLI1) Underlies the Growth Inhibitory Properties of Arachidonic Acid.
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 12 papers.
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Who cites it
12 citing papers in PubMed, 21 citations in OpenAlex.
- Combined fat and sugar intake reshapes the tumor microenvironment through hypoxia and lipogenic pathways in breast cancer.European journal of nutrition · 2026Article
- Nuclear Galectin-1 promotesProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Novel inhibitory effect of Omega-3 fatty acids regulating pancreatic cancer progression.Carcinogenesis · 2025Article
- Identification of the γ-glutamyl cycle as a novel therapeutic target and 5-oxoproline as a new biomarker for diagnosing pancreatic cancer.Annals of medicine · 2023Article
- Quinolines and Oxazino-quinoline Derivatives as Small Molecule GLI1 Inhibitors Identified by Virtual Screening.ACS medicinal chemistry letters · 2022Article
- Polyunsaturated Fatty Acid-Enriched Lipid Fingerprint of Glioblastoma Proliferative Regions Is Differentially Regulated According to Glioblastoma Molecular Subtype.International journal of molecular sciences · 2022Article
- RAS mutations drive proliferative chronic myelomonocytic leukemia via a KMT2A-PLK1 axis.Nature communications · 2021Article
- GLI1: A Therapeutic Target for Cancer.Frontiers in oncology · 2021Review
- Arginylated Calreticulin Increases Apoptotic Response Induced by Bortezomib in Glioma Cells.Molecular neurobiology · 2019Article
- NFATc1 is a tumor suppressor in hepatocellular carcinoma and induces tumor cell apoptosis by activating the FasL-mediated extrinsic signaling pathway.Cancer medicine · 2018Article
- Role and inhibition of GLI1 protein in cancer.Lung Cancer (Auckland, N.Z.) · 2018Review
- Cell cycle and apoptosis regulation by NFAT transcription factors: new roles for an old player.Cell death & disease · 2016Review
Corrections and comments
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Authors and funding
16 authors at 8 institutions in 4 countries.
Funding
Abstract
Numerous reports have demonstrated a tumor inhibitory effect of polyunsaturated fatty acids (PUFAs). However, the molecular mechanisms modulating this phenomenon are in part poorly understood. Here, we provide evidence of a novel antitumoral mechanism of the PUFA arachidonic acid (AA). In vivo and in vitro experiments showed that AA treatment decreased tumor growth and metastasis and increased apoptosis. Molecular analysis of this effect showed significantly reduced expression of a subset of antiapoptotic proteins, including BCL2, BFL1/A1, and 4-1BB, in AA-treated cells. We demonstrated that down-regulation of the transcription factor glioma-associated protein 1 (GLI1) in AA-treated cells is the underlying mechanism controlling BCL2, BFL1/A1, and 4-1BB expression. Using luciferase reporters, chromatin immunoprecipitation, and expression studies, we found that GLI1 binds to the promoter of these antiapoptotic molecules and regulates their expression and promoter activity. We provide evidence that AA-induced apoptosis and down-regulation of antiapoptotic genes can be inhibited by overexpressing GLI1 in AA-sensitive cells. Conversely, inhibition of GLI1 mimics AA treatments, leading to decreased tumor growth, cell viability, and expression of antiapoptotic molecules. Further characterization showed that AA represses GLI1 expression by stimulating nuclear translocation of NFATc1, which then binds the GLI1 promoter and represses its transcription. AA was shown to increase reactive oxygen species. Treatment with antioxidants impaired the AA-induced apoptosis and down-regulation of GLI1 and NFATc1 activation, indicating that NFATc1 activation and GLI1 repression require the generation of reactive oxygen species. Collectively, these results define a novel mechanism underlying AA antitumoral functions that may serve as a foundation for future PUFA-based therapeutic approaches.
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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 Socratic graph.