ArticleThe Biochemical journal2021
PEPT1 is essential for the growth of pancreatic cancer cells: a viable drug target.
Article in The Biochemical journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Hydrated proton complexes supplementation for tumor microenvironment reprogramming: a bioenergetic strategy targeting the Warburg effect and mitochondrial dysfunction.Frontiers in oncology · 2025Pooled it
- Dual targeting of SLC6A14 and autophagy/macropinocytosis enhances therapeutic efficacy in pancreatic ductal adenocarcinoma.The Biochemical journal · 2026Article
- Dipeptide Transport Systems at the Interface of Peptide Metabolism and Drug Delivery in Cancer.International journal of molecular sciences · 2026Review
- Arginine Transporters in Human Cancers: Emerging Mechanisms and Clinical Implications.Biomolecules · 2026Review
- Functional and Physiological Implications of Oligopeptide Transporters: Potential Targets for Pharmacological Interventions.The Journal of membrane biology · 2025Review
- The SLC-ome of membrane transport: From molecular discovery to physiology and clinical applications.Physiological reviews · 2025Review
- Lactic Acid and Glutamine Have Positive Synergistic Effects on Growth Performance, Intestinal Function, and Microflora of Weaning Piglets.Animals : an open access journal from MDPI · 2024Article
- Peptide Transporter 1-Mediated Dipeptide Transport Promotes Hepatocellular Carcinoma Metastasis by Activating MAP4K4/G3BP2 Signaling Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Single-cell analysis revealed a potential role of T-cell exhaustion in colorectal cancer with liver metastasis.Journal of cellular and molecular medicine · 2024Article
- Review
- Cell-based homologous expression system forCurrent research in physiology · 2024Article
- Amino acid transporter SLC38A5 is a tumor promoter and a novel therapeutic target for pancreatic cancer.Scientific reports · 2023Article
- Article
- The Role of Solute Carrier Transporters in Efficient Anticancer Drug Delivery and Therapy.Pharmaceutics · 2023Review
- Deletion of Slc6a14 reduces cancer growth and metastatic spread and improves survival in KPC mouse model of spontaneous pancreatic cancer.The Biochemical journal · 2022Article
- Unconventional Functions of Amino Acid Transporters: Role in Macropinocytosis (SLC38A5/SLC38A3) and Diet-Induced Obesity/Metabolic Syndrome (SLC6A19/SLC6A14/SLC6A6).Biomolecules · 2022Review
- Susceptibility Loci in SLC15A1, UGT1A3, and CWC27 Genes Associated with Bladder Cancer in the Northeast Chinese Population.BioMed research international · 2022Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
PEPT1 is a proton-coupled peptide transporter that is up-regulated in PDAC cell lines and PDXs, with little expression in the normal pancreas. However, the relevance of this up-regulation to cancer progression and the mechanism of up-regulation have not been investigated. Herein, we show that PEPT1 is not just up-regulated in a large panel of PDAC cell lines and PDXs but is also functional and transport-competent. PEPT2, another proton-coupled peptide transporter, is also overexpressed in PDAC cell lines and PDXs, but is not functional due to its intracellular localization. Using glibenclamide as a pharmacological inhibitor of PEPT1, we demonstrate in cell lines in vitro and mouse xenografts in vivo that inhibition of PEPT1 reduces the proliferation of the cancer cells. These findings are supported by genetic knockdown of PEPT1 with shRNA, wherein the absence of the transporter significantly attenuates the growth of cancer cells, both in vitro and in vivo, suggesting that PEPT1 is critical for the survival of cancer cells. We also establish that the tumor-derived lactic acid (Warburg effect) in the tumor microenvironment supports the transport function of PEPT1 in the maintenance of amino acid nutrition in cancer cells by inducing MMPs and DPPIV to generate peptide substrates for PEPT1 and by generating a H+ gradient across the plasma membrane to energize PEPT1. Taken collectively, these studies demonstrate a functional link between PEPT1 and extracellular protein breakdown in the tumor microenvironment as a key determinant of pancreatic cancer growth, thus identifying PEPT1 as a potential therapeutic target for PDAC.
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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 Socratic graph.