ArticleGut2022
Extracellular Vesicles from Pancreatic Cancer Stem Cells Lead an Intratumor Communication Network (EVNet) to fuel tumour progression.
Article in Gut, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 93 citations in OpenAlex.
- Translational insights and clinical challenges of targeting cancer stem cells.Signal transduction and targeted therapy · 2026Review
- Targeting RAB27A-mediated small extracellular vesicle secretion via CRISPR-Cas9 negatively affects proliferation and metastasis in both in vitro and in vivo SCLC models.Cancer gene therapy · 2026Article
- Isolation and Characterization of Extracellular Vesicles from Human and Mouse Pancreatic Tissue.Bioengineering (Basel, Switzerland) · 2026Article
- Extracellular vesicles in solid tumors: from tumor ecology to engineered therapeutics.Molecular cancer · 2026Review
- A Noncanonical RNA-Binding Function of NQO1 Drives Angiogenesis in Esophageal Squamous Cell Carcinoma via Extracellular Vesicle-Mediated AGRN Transfer.Cancer research · 2026Article
- Diagnostic and prognostic significance of circulating extracellular vesicles in gastrointestinal cancers.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- AGRN activates GPX4 via the Wnt/beta-catenin signaling pathway to suppress ferroptosis in cervical cancer cells.Briefings in functional genomics · 2026Article
- Extracellular vesicles from cytokine-treated human pancreatic ductal cells enhance HLA class I expression in beta cells.Frontiers in immunology · 2026Article
- Challenges and caveats in manipulating extracellular vesicle secretion from pancreatic cancer cells.Cancer biology & therapy · 2025Article
- Clinical relevance of extracellular vesicles in cancer - therapeutic and diagnostic potential.Nature reviews. Clinical oncology · 2025Review
- Targeting ferroptosis in cancer stem cells: A novel strategy to improve cancer treatment.Genes & diseases · 2025Review
- Advances of extracellular vesicles isolation and detection frontier technology: from heterogeneity analysis to clinical application.Journal of nanobiotechnology · 2025Review
- HuR-Regulated Extracellular Vesicles Promote Endothelial Cell Remodeling in Pancreatic Cancer.Cancer research communications · 2025Article
- The Impact of Peroxiredoxin 3 on Molecular Testing, Diagnosis, and Prognosis in Human Pancreatic Ductal Adenocarcinoma.Cancers · 2025Article
- Protrusion-Derived Extracellular Vesicles (PD-EVs) and Their Diverse Origins: Key Players in Cellular Communication, Cancer Progression, and T Cell Modulation.Biology of the cell · 2025Review
- Therapeutic efficacy of TMTP1-modified EVs in overcoming bone metastasis and immune resistance in PIK3CA mutant NSCLC.Cell death & disease · 2025Article
- An Agrin-YAP/TAZ Rigidity Sensing Module Drives EGFR-Addicted Lung Tumorigenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Tumor microenvironment as niche constructed by cancer stem cells: Breaking the ecosystem to combat cancer.Journal of advanced research · 2025Review
- A first-in-class inhibitor of homologous recombination DNA repair counteracts tumour growth, metastasis and therapeutic resistance in pancreatic cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- A model of basement membrane-related regulators for prediction of prognoses in esophageal cancer and verification in vitro.BMC cancer · 2025Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
26 authors at 9 institutions in 5 countries.
Funding
Abstract
objectiveIntratumor heterogeneity drives cancer progression and therapy resistance. However, it has yet to be determined whether and how subpopulations of cancer cells interact and how this interaction affects the tumour.
designWe have studied the spontaneous flow of extracellular vesicles (EVs) between subpopulations of cancer cells: cancer stem cells (CSC) and non-stem cancer cells (NSCC). To determine the biological significance of the most frequent communication route, we used pancreatic ductal adenocarcinoma (PDAC) orthotopic models, patient-derived xenografts (PDXs) and genetically engineered mouse models (GEMMs).
resultsWe demonstrate that PDAC tumours establish an organised communication network between subpopulations of cancer cells using EVs called the EVNet). The EVNet is plastic and reshapes in response to its environment. Communication within the EVNet occurs preferentially from CSC to NSCC. Inhibition of this communication route by impairing Rab27a function in orthotopic xenographs, GEMMs and PDXs is sufficient to hamper tumour growth and phenocopies the inhibition of communication in the whole tumour. Mechanistically, we provide evidence that CSC EVs use agrin protein to promote Yes1 associated transcriptional regulator (YAP) activation via LDL receptor related protein 4 (LRP-4). Ex vivo treatment of PDXs with antiagrin significantly impairs proliferation and decreases the levels of activated YAP.Patients with high levels of agrin and low inactive YAP show worse disease-free survival. In addition, patients with a higher number of circulating agrin
conclusionPDAC tumours establish a cooperation network mediated by EVs that is led by CSC and agrin, which allows tumours to adapt and thrive. Targeting agrin could make targeted therapy possible for patients with PDAC and has a significant impact on CSC that feeds the tumour and is at the centre of therapy resistance.
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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.