ArticleThe Journal of clinical investigation2014
Sphingosine-1-phosphate lyase downregulation promotes colon carcinogenesis through STAT3-activated microRNAs.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04398550 (Specific Carbohydrate Diet vs. Mediterranean Diet Therapy in Ulcerative Colitis - A Clinical Trial), which is not on this map. Cited by 94 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.
Specific Carbohydrate Diet vs. Mediterranean Diet Therapy in Ulcerative Colitis - A Clinical Trial
Who cites it
94 citing papers in PubMed, 150 citations in OpenAlex.
- Integrated plasma and duodenal content metabolomics reveals metabolic mechanisms underlying residual feed intake differences in broilers.Poultry science · 2026Article
- Exploring the Relationship Between Colitis-Associated Cancer and Lipid Metabolism Reprogramming from the Perspective of Inflammation-Cancer Transformation.Journal of inflammation research · 2026Review
- Exploring the biological functions of PCOS: identifying hub androgen-related genes through bioinformatics.Frontiers in medicine · 2026Article
- Article
- S1P Lyase Inhibition Increased Intestinal S1P, Disrupted the Intestinal Barrier and Aggravated DSS-Induced Colitis.Inflammatory bowel diseases · 2025Article
- Review
- Sphingosine-1-Phosphate Metabolic Pathway in Cancer: Implications for Therapeutic Targets.International journal of molecular sciences · 2025Review
- Advances in ORMDL Research in Malignant Tumors: A Review.OncoTargets and therapy · 2025Review
- Repurposing metformin as a potential anticancer agent using in silico technique.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2024Article
- The diverse roles of sphingolipids in inflammatory bowel disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Review
- Therapeutic Potential for Sphingolipids in Inflammatory Bowel Disease and Colorectal Cancer.Cancers · 2024Review
- S1P/S1PR1 signaling is involved in the development of nociceptive pain.Frontiers in pharmacology · 2024Article
- Multi-Anticancer Activities of Phytoestrogens in Human Osteosarcoma.International journal of molecular sciences · 2023Review
- Immune System and Brain/Intestinal Barrier Functions in Psychiatric Diseases: Is Sphingosine-1-Phosphate at the Helm?International journal of molecular sciences · 2023Review
- Mass Spectrometry Detects Sphingolipid Metabolites for Discovery of New Strategy for Cancer Therapy from the Aspect of Programmed Cell Death.Metabolites · 2023Review
- The Effect of Silencing the Genes Responsible for the Level of Sphingosine-1-phosphate on the Apoptosis of Colon Cancer Cells.International journal of molecular sciences · 2023Article
- Beneficial Effects of Hordenine on a Model of Ulcerative Colitis.Molecules (Basel, Switzerland) · 2023Article
- Unveiling the biological role of sphingosine-1-phosphate receptor modulators in inflammatory bowel diseases.World journal of gastroenterology · 2023Review
- Signal Transduction and Gene Regulation in the Endothelium.Cold Spring Harbor perspectives in medicine · 2023Review
- The role of sphingosine-1-phosphate in the gut mucosal microenvironment and inflammatory bowel diseases.Frontiers in physiology · 2023Review
34 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 3 countries.
Funding
Abstract
Growing evidence supports a link between inflammation and cancer; however, mediators of the transition between inflammation and carcinogenesis remain incompletely understood. Sphingosine-1-phosphate (S1P) lyase (SPL) irreversibly degrades the bioactive sphingolipid S1P and is highly expressed in enterocytes but downregulated in colon cancer. Here, we investigated the role of SPL in colitis-associated cancer (CAC). We generated mice with intestinal epithelium-specific Sgpl1 deletion and chemically induced colitis and tumor formation in these animals. Compared with control animals, mice lacking intestinal SPL exhibited greater disease activity, colon shortening, cytokine levels, S1P accumulation, tumors, STAT3 activation, STAT3-activated microRNAs (miRNAs), and suppression of miR-targeted anti-oncogene products. This phenotype was attenuated by STAT3 inhibition. In fibroblasts, silencing SPL promoted tumorigenic transformation through a pathway involving extracellular transport of S1P through S1P transporter spinster homolog 2 (SPNS2), S1P receptor activation, JAK2/STAT3-dependent miR-181b-1 induction, and silencing of miR-181b-1 target cylindromatosis (CYLD). Colon biopsies from patients with inflammatory bowel disease revealed enhanced S1P and STAT3 signaling. In mice with chemical-induced CAC, oral administration of plant-type sphingolipids called sphingadienes increased colonic SPL levels and reduced S1P levels, STAT3 signaling, cytokine levels, and tumorigenesis, indicating that SPL prevents transformation and carcinogenesis. Together, our results suggest that dietary sphingolipids can augment or prevent colon cancer, depending upon whether they are metabolized to S1P or promote S1P metabolism through the actions of SPL.
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What OpenQuestion holds
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.