ArticleJCI insight2022
Ceramide-mediated gut dysbiosis enhances cholesterol esterification and promotes colorectal tumorigenesis in mice.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 40 citations in OpenAlex.
- Unveiling the association between plasma lipid species and pan-cancers: A bidirectional 2-sample Mendelian randomization study.Medicine · 2026Article
- SPHK1 deficiency promotes intestinal homeostasis by ameliorating ER stress-induced gastrointestinal injury during murine graft-versus-host disease.Science China. Life sciences · 2026Article
- Lipid metabolism as a central driver of immune remodeling and therapeutic vulnerability in metastatic colorectal cancer.Lipids in health and disease · 2026Review
- Interplay Between Gut Microbiota and Cholesterol Metabolism in Colorectal Cancer.International journal of molecular sciences · 2026Review
- Targeting metabolic-epigenetic-immune axis in cancer: molecular mechanisms and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- [p53-SOAT1 Axis: A Novel Target for Tumor Lipid Metabolism and Therapy].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Review
- Lipid metabolic reprogramming in colorectal cancer: Insights to mechanisms and therapeutics.World journal of gastrointestinal oncology · 2025Review
- Astragaloside IV Alleviates Fructose-Induced Intestinal Metabolic Senescence by Targeting Ketohexokinase Asn261/Ala226 to Preserve Intestinal Stem Cell Homeostasis.ACS central science · 2025Article
- Microbial riboflavin inhibits ceramide synthase 3 to lower ceramide (d18:1/26:0) and delay colorectal cancer progression.Cell metabolism · 2025Article
- Global Research Trends and Hotspots in the Role of Cholesterol in Colorectal Cancer: A Bibliometric Analysis.Human mutation · 2025Article
- Gasdermin D regulates the activation of EGFR in colorectal cancer.Journal of translational medicine · 2024Article
- The diverse roles of sphingolipids in inflammatory bowel disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Review
- The Role of Natural Products from Herbal Medicine in TLR4 Signaling for Colorectal Cancer Treatment.Molecules (Basel, Switzerland) · 2024Review
- Comprehensive prognostic and immune analysis of sterol O-acyltransferase 1 in patients with hepatocellular carcinoma.World journal of hepatology · 2024Article
- Therapeutic Potential for Sphingolipids in Inflammatory Bowel Disease and Colorectal Cancer.Cancers · 2024Review
- RAS signaling and immune cells: a sinister crosstalk in the tumor microenvironment.Journal of translational medicine · 2023Review
- The ceramide synthase (CERS/LASS) family: Functions involved in cancer progression.Cellular oncology (Dordrecht, Netherlands) · 2023Review
- Blocking the Wnt/β‑catenin signaling pathway to treat colorectal cancer: Strategies to improve current therapies (Review).International journal of oncology · 2023Review
- Targeting sterol-O-acyltransferase 1 to disrupt cholesterol metabolism for cancer therapy.Frontiers in oncology · 2023Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Colorectal cancer (CRC) severely threatens human health and life span. An effective therapeutic strategy has not been established because we do not clearly know its pathogenesis. Here, we report that ceramide and sterol O-acyltransferase 1 (SOAT1) have roles in both spontaneous and chemical-induced intestinal cancers. We first found that miRNA-148a deficiency dramatically increased mouse gut dysbiosis through upregulating ceramide synthase 5 (Cers5) expression, which promoted ceramide synthesis afterward. The newly generated ceramide further promoted both azoxymethane/dextran sodium sulfate-induced (AOM/DSS-induced) and ApcMin/+ spontaneous intestinal tumorigenesis via increasing mouse gut dysbiosis. Meanwhile, increased level of ceramide correlated with the significant enhancements of both β-catenin activity and colorectal tumorigenesis in a TLR4-dependent fashion. Next, we found a direct binding of β-catenin to SOAT1 promoter to activate transcriptional expression of SOAT1, which further induced cholesterol esterification and colorectal tumorigenesis. In human patients with CRC, the same CERS5/TLR4/β-catenin/SOAT1 axis was also found to be dysregulated. Finally, the SOAT1 inhibitor (avasimibe) showed significant levels of therapeutic effects on both AOM/DSS-induced and ApcMin/+ spontaneous intestinal cancer. Our study clarified that ceramide promoted CRC development through increasing gut dysbiosis, further resulting in the increase of cholesterol esterification in a SOAT1-dependent way. Treatment with avasimibe to specifically decrease cholesterol esterification could be considered as a clinical strategy for effective CRC therapy in a future study.
Indexed as
Identifiers
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.