ArticleBiochemical pharmacology2015
Interference with distinct steps of sphingolipid synthesis and signaling attenuates proliferation of U87MG glioma cells.
Article in Biochemical pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Sphingosine 1-phosphate (S1P) signaling in glioblastoma multiforme-A systematic review.International journal of molecular sciences · 2017Pooled it
- Metabolic Landscape and Emerging Therapeutic Potential in Pediatric and Adult Gliomas.International journal of molecular sciences · 2026Review
- Targeting Metabolic Vulnerabilities in Glioblastoma: a Framework for Multi-node Combination Therapy.Current oncology reports · 2026Review
- Metabolic models predict fotemustine and the combination of eflornithine/rifamycin and adapalene/cannabidiol for the treatment of gliomas.Briefings in bioinformatics · 2024Article
- The role of sphingolipid rheostat in the adult-type diffuse glioma pathogenesis.Frontiers in cell and developmental biology · 2024Review
- Evaluation of Temozolomide and Fingolimod Treatments in Glioblastoma Preclinical Models.Cancers · 2023Article
- Lipid Alterations in Glioma: A Systematic Review.Metabolites · 2022Review
- Targeting the Sphingolipid Rheostat in Gliomas.International journal of molecular sciences · 2022Review
- Article
- Bioactive Compounds with Antiglioma Activity from Marine Species.Biomedicines · 2021Review
- Ceramide Metabolism Enzymes-Therapeutic Targets against Cancer.Medicina (Kaunas, Lithuania) · 2021Review
- Ceramide Metabolism and Parkinson's Disease-Therapeutic Targets.Biomolecules · 2021Review
- Ubiquitination Destabilizes Protein Sphingosine Kinase 2 to Regulate Glioma Malignancy.Frontiers in cellular neuroscience · 2021Article
- Sphingosine-1-Phosphate in the Tumor Microenvironment: A Signaling Hub Regulating Cancer Hallmarks.Cells · 2020Review
- Review
- Long and Very-Long-Chain Ceramides Correlate with A More Aggressive Behavior in Skull Base Chordoma Patients.International journal of molecular sciences · 2019Article
- S1PR1 promotes proliferation and inhibits apoptosis of esophageal squamous cell carcinoma through activating STAT3 pathway.Journal of experimental & clinical cancer research : CR · 2019Article
- S1PR1 as a Novel Promising Therapeutic Target in Cancer Therapy.Molecular diagnosis & therapy · 2019Review
- Statins improve survival in patients previously treated with nivolumab for advanced non-small cell lung cancer: An observational study.Molecular and clinical oncology · 2019Article
- Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Glioblastoma is the most common malignant brain tumor, which, despite combined radio- and chemotherapy, recurs and is invariably fatal for affected patients. Members of the sphingolipid (SL) family are potent effectors of glioma cell proliferation. In particular sphingosine-1-phosphate (S1P) and the corresponding G protein-coupled S1P receptors transmit proliferative signals to glioma cells. To investigate the contribution to glioma cell proliferation we inhibited the first step of de novo SL synthesis in p53(wt) and p53(mut) glioma cells, and interfered with S1P signaling specifically in p53(wt) U87MG cells. Subunit silencing (RNAi) or pharmacological antagonism (using myriocin) of serine palmitoyltransferase (SPT; catalyzing the first committed step of SL biosynthesis) reduced proliferation of p53(wt) but not p53(mut) GBM cells. In U87MG cells these observations were accompanied by decreased ceramide, sphingomyelin, and S1P content. Inhibition of SPT upregulated p53 and p21 expression and induced an increase in early and late apoptotic U87MG cells. Exogenously added S1P (complexed to physiological carriers) increased U87MG proliferation. In line, silencing of individual members of the S1P receptor family decreased U87MG proliferation. Silencing and pharmacological inhibition of the ATP-dependent cassette transporter A1 (ABCA1) that facilitates S1P efflux in astrocytes attenuated U87MG growth. Glyburide-mediated inhibition of ABCA1 resulted in intracellular accumulation of S1P raising the possibility that ABCA1 promotes S1P efflux in U87MG glioma cells thereby contributing to inside-out signaling. Our findings indicate that de novo SL synthesis, S1P receptor-mediated signaling, and ABCA1-mediated S1P efflux could provide pharmacological targets to interfere with glioma cell proliferation.
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Registered trials
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