ArticleJournal of experimental & clinical cancer research : CR2023
S1PR1/S1PR3-YAP signaling and S1P-ALOX15 signaling contribute to an aggressive behavior in obesity-lymphoma.
Article in Journal of experimental & clinical cancer research : CR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 19 citations in OpenAlex.
- Sphingosine-1-phosphate induces angiogenesis via the activating STAT3 signaling pathway to drive colorectal cancer progression.Journal of gastrointestinal oncology · 2026Article
- Review
- ALOX15 exerts tumor-suppressive role in head and neck squamous cell carcinoma via ERK pathway.Functional & integrative genomics · 2026Article
- Metabolic reprogramming in cancer: dysregulation of glucose, lipid, and amino acid pathways and therapeutic opportunities.Molecular biomedicine · 2026Review
- Metabolic reprogramming in tumor-associated cells of hematologic malignancies: mechanisms, crosstalk networks, and therapeutic implications in the tumor microenvironment.Frontiers in immunology · 2026Review
- The role of ALOX15 in inflammation-related diseases.Frontiers in immunology · 2026Review
- Remodeling the Tumor Microenvironment: Mechanistic Insights and Translational Frontiers of TCM-Derived Bioactive Monomers.Cancer management and research · 2026Review
- Aberrant lipid metabolism renders an aggressive behavior of T-lymphoblastic lymphoma in a MASH model.Oncogene · 2026Article
- Developing the risk prediction model (ProlncSig) from lipoxygenase pathway-related lncRNAs for prognosis prediction in breast cancer.RNA biology · 2025Article
- Intratumoral injection of R848 and poly(I:C) synergistically promoted antitumor immune responses by reprogramming macrophage polarization and activating DCs in lung cancer.Clinical and experimental immunology · 2025Article
- Identification of iron metabolism-related key genes and exploration of their potential mechanisms in hemophagocytic lymphohistiocytosis based on transcriptome sequencing.Frontiers in medicine · 2025Article
- Spatiotemporal sphingosine-1-phosphate receptor 3 expression within the cerebral vasculature after ischemic stroke.iScience · 2024Article
- Signaling controversy and future therapeutical perspectives of targeting sphingolipid network in cancer immune editing and resistance to tumor necrosis factor-α immunotherapy.Cell communication and signaling : CCS · 2024Review
- Lipoxygenases at the Intersection of Infection and Carcinogenesis.International journal of molecular sciences · 2024Review
- Role for CCN1 in lysophosphatidic acid response in PC-3 human prostate cancer cells.Journal of cell communication and signaling · 2024Article
- Targeting natural killer cells: from basic biology to clinical application in hematologic malignancies.Experimental hematology & oncology · 2024Review
- Article
- Resveratrol-driven macrophage polarization: unveiling mechanisms and therapeutic potential.Frontiers in pharmacology · 2024Review
- Targeting sphingosine kinase 1 in p53KO thymic lymphoma.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundExcess body weight has been found to associate with an increased risk of lymphomas and some metabolic pathways are currently recognized in lymphomagenesis. Bioactive lipid metabolites such as sphingosine-1-phosphate (S1P) have been proposed to play an important role linking obesity and lymphomas. However, the underlying mechanism(s) of S1P signaling in obesity-lymphomagenesis have not been well addressed.
methodsThe gene expression of sphingosine kinase (SPHK), lymphoma prognosis, and S1P production were analyzed using Gene Expression Omnibus (GEO) and human lymphoma tissue array. Obesity-lymphoma mouse models and lymphoma cell lines were used to investigate the S1P/SPHK-YAP axis contributing to obesity-lymphomagenesis. By using the mouse models and a monocyte cell line, S1P-mediated polarization of macrophages in the tumor microenvironment were investigated.
resultsIn human study, up-regulated S1P/SPHK1 was found in human lymphomas, while obesity negatively impacted progression-free survival and overall survival in lymphoma patients. In animal study, obesity-lymphoma mice showed an aggressive tumor growth pattern. Both in vivo and in vitro data suggested the existence of S1P-YAP axis in lymphoma cells, while the S1P-ALOX15 signaling mediated macrophage polarization towards TAMs exacerbated the lymphomagenesis. In addition, treatment with resveratrol in obesity-lymphoma mice showed profound effects of anti-lymphomagenesis, via down-regulating S1P-YAP axis and modulating polarization of macrophages.
conclusionS1P/S1PR initiated the feedback loops, whereby S1P-S1PR1/S1PR3-YAP signaling mediated lymphomagenesis contributing to tumor aggressive growth, while S1P-ALOX15 signaling mediated TAMs contributing to immunosuppressive microenvironment in obesity-lymphoma. S1P-targeted therapy could be potentially effective and immune-enhancive against obesity-lymphomagenesis.
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Registered trials
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