ArticleEBioMedicine2019
Tumor cells hijack enteric glia to activate colon cancer stem cells and stimulate tumorigenesis.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 71 citations in OpenAlex.
- EGFR-dependent delivery of phosphorylated IGFBP3 by cancer stem cells drives chemotherapy resistance in colorectal cancer.Cell death & disease · 2026Article
- Neural cues differentially modulate colorectal cancer cell behavior depending on patients' genomic background.iScience · 2026Article
- enGLOW 3D microscopy of the enteric nervous system in cleared human and mouse gut.Communications biology · 2026Article
- Enteric nervous system and inflammatory bowel disease.Gastroenterology report · 2026Review
- From neuro-immune command circuits to microbiota-mediated regulation in the gastrointestinal tumor microenvironment.Frontiers in immunology · 2026Review
- Rodent Enteric Glia Culture.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Differentiating Enteric Glial Cells Within Intestinal Organoids Derived from Human Pluripotent Stem Cells.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Enteric neuro-immune-tumor ecosystem in pancreatic, colorectal, and gastric malignancies: context dependence and translational priorities.Frontiers in immunology · 2026Review
- Peripheral Nerve-Cancer Interactions in the Tumor Microenvironment: A Three-Dimensional Framework Integrating Mechanisms, Modulators, and Therapeutic Strategies.Research (Washington, D.C.) · 2026Review
- Gene Therapy in Crohn's Disease: Current Preclinical Challenges and Future Translational Avenues.Biomedicines · 2025Review
- Disease-specific alterations of the enteric nervous system in precancerous colonic mucosa and their implications for mucin regulation.Scientific reports · 2025Article
- The neuro-immune axis in cancer: from mechanisms to therapeutic opportunities.Journal of hematology & oncology · 2025Review
- Clinicopathological characterization of enteric glia in colorectal cancer: Insights from a population-based cohort.Journal of neuropathology and experimental neurology · 2025Article
- Innovative Therapeutic Approach Targeting Colon Cancer Stem Cells: Transitional Cold Atmospheric Plasma.ACS omega · 2025Article
- The Physiology of Enteric Glia.Annual review of physiology · 2025Review
- Nerves at Play: The Peripheral Nervous System in Extracranial Malignancies.Cancer discovery · 2025Review
- Neuro-Mesenchymal Interaction Mediated by a β2-Adrenergic Nerve Growth Factor Feedforward Loop Promotes Colorectal Cancer Progression.Cancer discovery · 2025Article
- Imaging the enteric nervous system.Frontiers in neuroanatomy · 2025Review
- AI-powered 3D pathology protocol enhances enteric nervous system visualization and quantification for clinical diagnostics.Theranostics · 2025Article
- Advancements in 3D In Vitro Models for Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundColon cancer stem cells (CSCs), considered responsible for tumor initiation and cancer relapse, are constantly exposed to regulatory cues emanating from neighboring cells present in the tumor microenvironment. Among these cells are enteric glial cells (EGCs) that are potent regulators of the epithelium functions in a healthy intestine. However, whether EGCs impact CSC-driven tumorigenesis remains unknown.
methodsImpact of human EGC primary cultures or a non-transformed EGC line on CSCs isolated from human primary colon adenocarcinomas or colon cancer cell lines with different p53, MMR system and stemness status was determined using murine xenograft models and 3D co-culture systems. Supernatants of patient-matched human primary colon adenocarcinomas and non-adjacent healthy mucosa were used to mimic tumor versus healthy mucosa secretomes and compare their effects on EGCs.
findingsOur data show that EGCs stimulate CSC expansion and ability to give rise to tumors via paracrine signaling. Importantly, only EGCs that were pre-activated by tumor epithelial cell-derived soluble factors increased CSC tumorigenicity. Pharmacological inhibition of PGE2 biosynthesis in EGCs or IL-1 knockdown in tumor epithelial cells prevented EGC acquisition of a pro-tumorigenic phenotype. Inhibition of PGE2 receptor EP4 and EGFR in CSCs inhibited the effects of tumor-activated EGCs.
interpretationAltogether, our results show that EGCs, once activated by the tumor, acquire a pro-tumorigenic phenotype and stimulate CSC-driven tumorigenesis via a PGE2/EP4/EGFR-dependent pathway.
fundingThis work was supported by grants from the French National Cancer Institute, La Ligue contre le Cancer, the 'Région des Pays de la Loire' and the UNC Lineberger Comprehensive Cancer Center.
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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.