ArticleCellular and molecular gastroenterology and hepatology2016
Critical role of PepT1 in promoting colitis-associated cancer and therapeutic benefits of the anti-inflammatory PepT1-mediated tripeptide KPV in a murine model.
Article in Cellular and molecular gastroenterology and hepatology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 34 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Eudragit-Based Nanoparticles for Oral Drug Delivery.Pharmaceutics · 2026Review
- Therapeutic Peptides in Aesthetic, Metabolic and Endocrine Conditions: Effects, Safety, Clinical Applications, and Future Perspectives.International journal of molecular sciences · 2026Review
- Administration of the NOD2 Agonist MDP Reduces Cryptosporidium parvum Infection in Neonatal Mice Through IL-22 Involvement.European journal of immunology · 2025Article
- Extracellular Vesicles of the ProbioticNutrients · 2024Article
- Peptide Transporter 1-Mediated Dipeptide Transport Promotes Hepatocellular Carcinoma Metastasis by Activating MAP4K4/G3BP2 Signaling Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Molecular Insights to the Structure-Interaction Relationships of Human Proton-Coupled Oligopeptide Transporters (PepTs).Pharmaceutics · 2023Review
- Transport of Biologically Active Ultrashort Peptides Using POT and LAT Carriers.International journal of molecular sciences · 2022Review
- Supplementation with High or Low Iron Reduces Colitis Severity in an AOM/DSS Mouse Model.Nutrients · 2022Article
- Rab21 in enterocytes participates in intestinal epithelium maintenance.Molecular biology of the cell · 2022Article
- PEPT1 is essential for the growth of pancreatic cancer cells: a viable drug target.The Biochemical journal · 2021Article
- SLC15A4 Serves as a Novel Prognostic Biomarker and Target for Lung Adenocarcinoma.Frontiers in genetics · 2021Article
- Oral Delivery of Biologics in Inflammatory Bowel Disease Treatment.Frontiers in bioengineering and biotechnology · 2021Review
- Review
- Impact of PepT1 deletion on microbiota composition and colitis requires multiple generations.NPJ biofilms and microbiomes · 2020Article
- Function, Regulation, and Pathophysiological Relevance of the POT Superfamily, Specifically PepT1 in Inflammatory Bowel Disease.Comprehensive Physiology · 2018Review
- Regulation profile of the intestinal peptide transporter 1 (PepT1).Drug design, development and therapy · 2017Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 2 countries.
Funding
Abstract
BACKGROUND AND
aimsThe human intestinal peptide transporter 1, hPepT1, is expressed in the small intestine at low levels in the healthy colon and upregulated during inflammatory bowel disease. hPepT1 plays a role in mouse colitis and human studies have demonstrated that chronic intestinal inflammation leads to colorectal cancer (colitis-associated cancer; CAC). Hence, we assessed here the role of PepT1 in CAC.
methodsMice with hPepT1 overexpression in intestinal epithelial cells (TG) or PepT1 (PepT1-KO) deletion were used and CAC was induced by AOM/DSS.
resultsTG mice had larger tumor sizes, increased tumor burdens, and increased intestinal inflammation compared to WT mice. Conversely, tumor number and size and intestinal inflammation were significantly decreased in PepT1-KO mice. Proliferating crypt cells were increased in TG mice and decreased in PepT1-KO mice. Analysis of human colonic biopsies revealed an increased expression of PepT1 in patients with colorectal cancer, suggesting that PepT1 might be targeted for the treatment of CAC. The use of an anti-inflammatory tripeptide KPV (Lys-Pro-Val) transported by PepT1 was able to prevent carcinogenesis in WT mice. When administered to PepT1-KO mice, KPV did not trigger any of the inhibitory effect on tumorigenesis observed in WT mice.
conclusionsThe observations that pepT1 was highly expressed in human colorectal tumor and that its overexpression and deletion in mice increased and decreased colitis associated tumorigenesis, respectively, suggest that PepT1 is a potential therapeutic target for the treatment of colitis associated tumorigenesis.
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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.