ArticleCell death & disease2011
S1P lyase regulates DNA damage responses through a novel sphingolipid feedback mechanism.
Article in Cell death & disease, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06864221 (Correlation Between Plasma Sphingolipid Metabolites and the Efficacy of Radiotherapy in Hepatocellular Carcinoma), which is not on this map. Cited by 34 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Correlation Between Plasma Sphingolipid Metabolites and the Efficacy of Radiotherapy in Hepatocellular Carcinoma
Who cites it
34 citing papers in PubMed, 43 citations in OpenAlex.
- Sphingosine kinase 1 is dysregulated via hypoxia-inducible factor 1α in oral squamous cell carcinoma.The Indian journal of medical research · 2026Article
- Molecular Mechanism and Research Progress of Sphingolipid Metabolism in Regulating Radiation-induced Apoptosis Using Pan-cancer Analysis.Current cancer drug targets · 2026Review
- Targeting ORMDL2 in glioblastoma through integrated landscape of high-throughput sequencing and pharmacogenomic analysis.International journal of medical sciences · 2025Article
- The role of lipid metabolism in cancer radioresistance.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Review
- Sphingosine-1-Phosphate Alleviates Irradiation Induced Salivary Gland Hypofunction through Preserving Endothelial Cells and Resident Macrophages.Antioxidants (Basel, Switzerland) · 2022Article
- Sphingosine-1 Phosphate Lyase Regulates Sensitivity of Pancreatic Beta-Cells to Lipotoxicity.International journal of molecular sciences · 2021Article
- Multi-Omics Integration Highlights the Role of Ubiquitination in CClInternational journal of molecular sciences · 2020Article
- SGPL1Cancer gene therapy · 2020Article
- Serum Metabolomic Alterations Associated with Cesium-137 Internal Emitter Delivered in Various Dose Rates.Metabolites · 2020Article
- Modulation of DNA Damage Response by Sphingolipid Signaling: An Interplay that Shapes Cell Fate.International journal of molecular sciences · 2020Review
- Prognostic roles of the expression of sphingosine-1-phosphate metabolism enzymes in non-small cell lung cancer.Translational lung cancer research · 2019Article
- Sphingosine kinase 1-associated autophagy differs between neurons and astrocytes.Cell death & disease · 2018Article
- Divergent Role of Sphingosine 1-Phosphate in Liver Health and Disease.International journal of molecular sciences · 2018Review
- First evidence of SGPL1 expression in the cell membrane silencing the extracellular S1P siren in mammary epithelial cells.PloS one · 2018Article
- Targeting Sphingosine Kinase Isoforms Effectively Reduces Growth and Survival of Neoplastic Mast Cells With D816V-KIT.Frontiers in immunology · 2018Article
- Endogenous Sphingolipid Signaling Pathway Implicated in the Action of Croton membranaceus on the Prostate Gland in BPH Patients.Medicines (Basel, Switzerland) · 2017Article
- S1P Lyase Regulation of Thymic Egress and Oncogenic Inflammatory Signaling.Mediators of inflammation · 2017Review
- DNA damage response and sphingolipid signaling in liver diseases.Surgery today · 2016Review
- A facile stable-isotope dilution method for determination of sphingosine phosphate lyase activity.Chemistry and physics of lipids · 2016Article
- Emerging role of sphingosine-1-phosphate signaling in head and neck squamous cell carcinoma.OncoTargets and therapy · 2016Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
The injurious consequences of ionizing radiation (IR) to normal human cells and the acquired radioresistance of cancer cells represent limitations to cancer radiotherapy. IR induces DNA damage response pathways that orchestrate cell cycle arrest, DNA repair or apoptosis such that irradiated cells are either repaired or eliminated. Concomitantly and independent of DNA damage, IR activates acid sphingomyelinase (ASMase), which generates ceramide, thereby promoting radiation-induced apoptosis. However, ceramide can also be metabolized to sphingosine-1-phosphate (S1P), which acts paradoxically as a radioprotectant. Thus, sphingolipid metabolism represents a radiosensitivity pivot point, a notion supported by genetic evidence in IR-resistant cancer cells. S1P lyase (SPL) catalyzes the irreversible degradation of S1P in the final step of sphingolipid metabolism. We show that SPL modulates the kinetics of DNA repair, speed of recovery from G2 cell cycle arrest and the extent of apoptosis after IR. SPL acts through a novel feedback mechanism that amplifies stress-induced ceramide accumulation, and downregulation/inhibition of either SPL or ASMase prevents premature cell cycle progression and mitotic death. Further, oral administration of an SPL inhibitor to mice prolonged their survival after exposure to a lethal dose of total body IR. Our findings reveal SPL to be a regulator of ASMase, the G2 checkpoint and DNA repair and a novel target for radioprotection.
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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.