ArticleClinical and translational medicine2022
Sphingosine 1-phosphate lyase facilitates cancer progression through converting sphingolipids to glycerophospholipids.
Article in Clinical and translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21 citing papers in PubMed, 36 citations in OpenAlex.
- Single-Cell RNA Sequencing Reveals T-Cell Metabolic Activation and SGPL1 as a Candidate Predictor of PD-1 Resistance in Urothelial Carcinoma.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Molecular Mechanism and Research Progress of Sphingolipid Metabolism in Regulating Radiation-induced Apoptosis Using Pan-cancer Analysis.Current cancer drug targets · 2026Review
- C-reactive protein modulates lipid mediators in a pro-inflammatory direction.Journal of inflammation (London, England) · 2025Article
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- Mechanism research on inhibition of gastric cancerOpen medicine (Warsaw, Poland) · 2025Article
- Protective Role of Sphingosine-1-Phosphate During Radiation-Induced Testicular Injury.Antioxidants (Basel, Switzerland) · 2024Review
- Regulation of cellular and systemic sphingolipid homeostasis.Nature reviews. Molecular cell biology · 2024Review
- Factors influencing survival in sphingosine phosphate lyase insufficiency syndrome: a retrospective cross-sectional natural history study of 76 patients.Orphanet journal of rare diseases · 2024Article
- Sphingosine kinase 2 and p62 regulation are determinants of sexual dimorphism in hepatocellular carcinoma.Molecular metabolism · 2024Article
- Identification of the Metabolic Signature of Aging Retina.Translational vision science & technology · 2024Article
- Article
- Development of an advanced liquid chromatography-tandem mass spectrometry measurement system for simultaneous sphingolipid analysis.Scientific reports · 2024Article
- Critical Roles of the Sphingolipid Metabolic Pathway in Liver Regeneration, Hepatocellular Carcinoma Progression and Therapy.Cancers · 2024Review
- Identification of pre-diagnostic lipid sets associated with liver cancer risk using untargeted lipidomics and chemical set analysis: A nested case-control study within the ATBC cohort.International journal of cancer · 2024Article
- Utilizing serum metabolomics for assessing postoperative efficacy and monitoring recurrence in gastric cancer patients.BMC cancer · 2024Article
- Alzheimer's disease manifests abnormal sphingolipid metabolism.Frontiers in aging neuroscience · 2024Article
- Sphingosine 1-Phosphate Lyase in the Developing and Injured Nervous System: a Dichotomy?Molecular neurobiology · 2023Review
- The combined signatures of G protein-coupled receptor family and immune landscape provide a prognostic and therapeutic biomarker in endometrial carcinoma.Journal of cancer research and clinical oncology · 2023Article
- The role of sphingosine-1-phosphate in autophagy and related disorders.Cell death discovery · 2023Review
- Prognostic signatures of sphingolipids: Understanding the immune landscape and predictive role in immunotherapy response and outcomes of hepatocellular carcinoma.Frontiers in immunology · 2023Article
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn addition to potent agonist properties for sphingosine 1-phosphate (S1P) receptors, intracellularly, S1P is an intermediate in metabolic conversion pathway from sphingolipids to glycerolysophospholipids (glyceroLPLs). We hypothesized that this S1P metabolism and its products might possess some novel roles in the pathogenesis of cancer, where S1P lyase (SPL) is a key enzyme.
methodsThe mRNA levels of sphingolipid-related and other cancer-related factors were measured in human hepatocellular carcinoma (HCC), colorectal cancer, and esophageal cancer patients' tumours and in their adjacent non-tumour tissues. Phospholipids (PL) and glyceroLPLs were measured by using liquid chromatography-tandem mass spectrometry (LC-MS/MS). In-vitro experiments were performed in Colon 26 cell line with modulation of the SPL and GPR55 expressions. Xenograft model was used for determination of the cancer progression and for pharmacological influence.
resultsBesides high SPL levels in human HCC and colon cancer, SPL levels were specifically and positively linked with levels of glyceroLPLs, including lysophosphatidylinositol (LPI). Overexpression of SPL in Colon 26 cells resulted in elevated levels of LPI and lysophosphatidylglycerol (LPG), which are agonists of GPR55. SPL overexpression-enhanced cell proliferation was inhibited by GPR55 silencing. Conversely, inhibition of SPL led to the opposite outcome and reversed by adding LPI, LPG, and metabolites generated during S1P degradation, which is regulated by SPL. The xenograft model results suggested the contribution of SPL and glyceroLPLs to tumour progression depending on levels of SPL and GPR55. Moreover, the pharmacological inhibition of SPL prevented the progression of cancer. The underlying mechanisms for the SPL-mediated cancer progression are the activation of p38 and mitochondrial function through the LPI, LPG-GPR55 axis and the suppression of autophagy in a GPR55-independent manner.
conclusionA new metabolic pathway has been proposed here in HCC and colon cancer, SPL converts S1P to glyceroLPLs, mainly to LPI and LPG, and facilitates cancer development.
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