ArticleGastroenterology2017
Gastrin Induces Nuclear Export and Proteasome Degradation of Menin in Enteric Glial Cells.
Article in Gastroenterology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 38 citations in OpenAlex.
- Extracellular signalling regulates gastrin transcription through site-specific phosphorylation and nuclear redistribution of Menin.bioRxiv : the preprint server for biology · 2026Article
- Hedgehog signaling drives glial cell plasticity and oncogenic reprogramming in gastroenteropancreatic neuroendocrine neoplasms.Molecular cancer · 2026Article
- Enteric nervous system and inflammatory bowel disease.Gastroenterology report · 2026Review
- The Physiology of Enteric Glia.Annual review of physiology · 2025Review
- Menin in Cancer.Genes · 2024Review
- Dihydroartemisinin Modulates Enteric Glial Cell Heterogeneity to Alleviate Colitis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- MEN1 deficiency stabilizes PD-L1 and promotes tumor immune evasion of lung cancer.Cancer science · 2024Article
- Spatial profiling reveals tissue-specific neuro-immune interactions in gastroenteropancreatic neuroendocrine tumors.The Journal of pathology · 2024Article
- From diversity to disease: unravelling the role of enteric glial cells.Frontiers in immunology · 2024Review
- Clinically Defined Mutations inCancer research communications · 2023Article
- Functional Intraregional and Interregional Heterogeneity between Myenteric Glial Cells of the Colon and Duodenum in Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- The gut brain in a dish: Murine primary enteric nervous system cell cultures.Neurogastroenterology and motility · 2022Review
- Gastrin: From Physiology to Gastrointestinal Malignancies.Function (Oxford, England) · 2022Review
- Genome analysis identifies differences in the transcriptional targets of duodenal versus pancreatic neuroendocrine tumours.BMJ open gastroenterology · 2021Article
- Enteric glia in homeostasis and disease: From fundamental biology to human pathology.iScience · 2021Review
- Enteric glial biology, intercellular signalling and roles in gastrointestinal disease.Nature reviews. Gastroenterology & hepatology · 2021Review
- Proton Pump Inhibitor Use, Hypergastrinemia, and Gastric Carcinoids-What Is the Relationship?International journal of molecular sciences · 2020Review
- Enteric Glia Play a Critical Role in Promoting the Development of Colorectal Cancer.Frontiers in oncology · 2020Article
- GLP-1 signaling suppresses menin's transcriptional block by phosphorylation in β cells.The Journal of cell biology · 2019Article
- High-fluence low-power laser irradiation promotes odontogenesis and inflammation resolution in periodontitis by enhancing stem cell proliferation and differentiation.International journal of molecular medicine · 2018Article
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Authors and funding
18 authors at 3 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsThe multiple endocrine neoplasia, type 1 (MEN1) locus encodes the nuclear protein and tumor suppressor menin. MEN1 mutations frequently cause neuroendocrine tumors such as gastrinomas, characterized by their predominant duodenal location and local metastasis at time of diagnosis. Diffuse gastrin cell hyperplasia precedes the appearance of MEN1 gastrinomas, which develop within submucosal Brunner's glands. We investigated how menin regulates expression of the gastrin gene and induces generation of submucosal gastrin-expressing cell hyperplasia.
methodsPrimary enteric glial cultures were generated from the VillinCre:Men1
resultsEnteric glial cells that stained positive for glial fibrillary acidic protein (GFAP+) expressed gastrin de novo through a mechanism that required PKA. Gastrin-induced nuclear export of menin via cholecystokinin B receptor (CCKBR)-mediated activation of PKA. Once exported from the nucleus, menin was ubiquitinated and degraded by the proteasome. GFAP and other markers of enteric glial cells (eg, p75 and S100B), colocalized with gastrin in human duodenal gastrinomas.
conclusionsMEN1-associated gastrinomas, which develop in the submucosa, might arise from enteric glial cells through hormone-dependent PKA signaling. This pathway disrupts nuclear menin function, leading to hypergastrinemia and associated sequelae.
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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.