ArticleBMC cancer2015
NPC1L1 knockout protects against colitis-associated tumorigenesis in mice.
Article in BMC cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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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.
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Who cites it
33 citing papers in PubMed, 53 citations in OpenAlex.
- Gut microbial β-glucuronidases and their role in the microbiome-metabolite axis in colorectal cancer.Nature communications · 2025Article
- The CBS/H2S axis regulates intestinal stem cell homeostasis and radiation-induced intestinal damage.Stem cell research & therapy · 2025Article
- Real-world evidence on the additional cancer risk reduction of ezetimibe: a 10-year nationwide retrospective cohort study emulating a target trial.Journal of cancer research and clinical oncology · 2025Article
- Intracellular cholesterol: new functions and therapeutic approaches in NSCLC EGFR-TKI resistance.Lipids in health and disease · 2025Review
- Mendelian Randomization Assessment of the Genetic Effects of Lipid-Lowering Drugs on Digestive System Cancers.Food science & nutrition · 2025Article
- Research progress on cholesterol metabolism and tumor therapy.Discover oncology · 2025Review
- Ezetimibe Anticancer Activity via the p53/Mdm2 Pathway.Biomedicines · 2025Article
- Efficacies of radiotherapy in rectal cancer patients treated with total mesorectal excision or other types of surgery: an updated meta-analysis.Oncology reviews · 2025Review
- Circulating lipids, lipid-lowering drug targets, and breast cancer risk: Comprehensive evidence from Mendelian randomization and summary data-based Mendelian randomization.Cancer causes & control : CCC · 2024Article
- Co-Expression of Niemann-Pick Type C1-Like1 (NPC1L1) with ACE2 Receptor Synergistically Enhances SARS-CoV-2 Entry and Fusion.Biomedicines · 2024Article
- Inhibition of PCSK9: A Promising Enhancer for Anti-PD-1/PD-L1 Immunotherapy.Research (Washington, D.C.) · 2024Review
- Cholesterol metabolism in tumor microenvironment: cancer hallmarks and therapeutic opportunities.International journal of biological sciences · 2024Review
- NPC1L1 Plays a Novel Role in Nonalcoholic Fatty Liver Disease.ACS omega · 2023Review
- Review
- Dysregulation of Cholesterol Homeostasis in Ovarian Cancer.Current oncology (Toronto, Ont.) · 2023Review
- Article
- Curcumin suppresses cell proliferation and reduces cholesterol absorption in Caco-2 cells by activating the TRPA1 channel.Lipids in health and disease · 2023Article
- The role of cholesterol metabolism in tumor therapy, from bench to bed.Frontiers in pharmacology · 2023Review
- Crosstalk between cholesterol metabolism and psoriatic inflammation.Frontiers in immunology · 2023Review
- Ezetimibe and Cancer: Is There a Connection?Frontiers in pharmacology · 2022Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundColorectal cancer is strongly associated with lipid metabolism. NPC1L1, a sterol transporter, plays a key role in modulating lipid homeostasis in vivo. Its inhibitor, ezetimibe, began to be used clinically to lower cholesterol and this caused the great debate on its role in causing carcinogenesis. Here we explored the role of NPC1L1 in colorectal tumorigenesis.
methodsWild-type mice and NPC1L1(-/-) (NPC1L1 knockout) mice were treated with azoxymethane (AOM)-dextran sodium sulfate (DSS) to induce colitis-associated colorectal tumorigenesis. Mice were sacrificed 10, 15, 18 or 20 weeks after AOM treatment, respectively. Colorectal tumors were counted and analyzed. Plasma lipid concentrations were measured using enzymatic reagent kit. Protein expression level was assayed by western blot.
resultsNPC1L1(-/-) mice significantly had fewer tumors than wild-type. The ratio of malignant/tumor in NPC1L1(-/-) mice was significantly lower than in wild-type 20 weeks after AOM-DSS treatment. NPC1L1 was highly expressed in the small intestine of wild-type mice but its expression was undetectable in colorectal mucous membranes or tumors in either group. NPC1L1 knockout decreased plasma total cholesterol and phospholipid. NPC1L1(-/-) mice had significant lower intestinal inflammation scores and expressed inflammatory markers p-c-Jun, p-ERK and Caspase-1 p20 lower than wild-type. NPC1L1 knockout also reduced lymphadenectasis what may be caused by inflammation. NPC1L1 knockout in mice decreased β-catenin in tumors and regulated TGF-β and p-gp in adjacent colons or tumors. There was not detectable change of p53 by NPC1L1 knockout.
conclusionsOur results provide the first evidence that NPC1L1 knockout protects against colitis-associated tumorigenesis. NPC1L1 knockout decreasing plasma lipid, especially cholesterol, to reduce inflammation and decreasing β-catenin, p-c-Jun and p-ERK may be involved in the mechanism.
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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.