ArticleGut2015
CCK2R identifies and regulates gastric antral stem cell states and carcinogenesis.
Article in Gut, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
71 citing papers in PubMed, 108 citations in OpenAlex.
- Review
- B-Cell Lymphoma-Extra Large Promotes Gastric Tumorigenesis via Apoptosis-Independent Wnt-β-Catenin Activation and Peroxisome Proliferator-Activated Receptor γ Suppression.Cellular and molecular gastroenterology and hepatology · 2026Article
- Progastrin, annexin A2, and tumor-associated macrophages in gastric adenocarcinoma.Journal of pathology and translational medicine · 2026Article
- Gastrin-dependent expansion of Cck2rGut · 2026Article
- Perspectives on gastric cancer: the central role of gastrin in carcinogenesis byFrontiers in oncology · 2026Review
- Gastric dilation following vertical sleeve gastrectomy reflects adaptive stem cell-driven regeneration without association with weight regain or increased cancer risk.Life sciences · 2025Article
- ARID1A mutation drives gastric tumorigenesis via activating type 2 immune dominant microenvironment.iScience · 2025Article
- Clinicopathological significance of histological diversity in gastric adenocarcinoma with primitive enterocyte phenotype: A methylation-driven aggressive entity.World journal of gastroenterology · 2025Article
- The plasticity of epithelial cells and its potential in the induced differentiation of gastric cancer.Cell death discovery · 2024Review
- CCKBR+ cancer cells contribute to the intratumor heterogeneity of gastric cancer and confer sensitivity to FOXO inhibition.Cell death and differentiation · 2024Article
- A Natural Peptide from A Traditional Chinese Medicine Has the Potential to Treat Chronic Atrophic Gastritis by Activating Gastric Stem Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Review
- Progastrin: An Overview of Its Crucial Role in the Tumorigenesis of Gastrointestinal Cancers.Biomedicines · 2024Review
- Helicobacter pylori-activated fibroblasts as a silent partner in gastric cancer development.Cancer metastasis reviews · 2023Review
- RNA recording in single bacterial cells using reprogrammed tracrRNAs.Nature biotechnology · 2023Article
- The composition and roles of gastric stem cells in epithelial homeostasis, regeneration, and tumorigenesis.Cellular oncology (Dordrecht, Netherlands) · 2023Review
- Spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium.Protein & cell · 2023Article
- SOX9 Modulates the Transformation of Gastric Stem Cells Through Biased Symmetric Cell Division.Gastroenterology · 2023Article
- Dissection of gastric homeostasis in vivo facilitates permanent capture of isthmus-like stem cells in vitro.Nature cell biology · 2023Article
- Gastric Stem Cell Biology and Helicobacter pylori Infection.Current topics in microbiology and immunology · 2023Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 7 institutions in 5 countries.
Funding
Abstract
objectiveProgastrin is the incompletely cleaved precursor of gastrin that is secreted by G-cells in the gastric antrum. Both gastrin and progastrin bind to the CCK2 receptor (Cckbr or CCK2R) expressed on a subset of gastric epithelial cells. Little is known about how gastrin peptides and CCK2R regulate gastric stem cells and carcinogenesis. Interconversion among progenitors in the intestine is documented, but the mechanisms by which this occurs are poorly defined.
designWe generated CCK2R-CreERT mice and performed inducible lineage tracing experiments. CCK2R+ antral cells and Lgr5+ antral stem cells were cultured in a three-dimensional in vitro system. We crossed progastrin-overexpressing mice with Lgr5-GFP-CreERT mice and examined the role of progastrin and CCK2R in Lgr5+ stem cells during MNU-induced carcinogenesis.
resultsThrough lineage tracing experiments, we found that CCK2R defines antral stem cells at position +4, which overlapped with an Lgr5(neg or low) cell population but was distinct from typical antral Lgr5(high) stem cells. Treatment with progastrin interconverts Lgr5(neg or low) CCK2R+ cells into Lgr5(high) cells, increases CCK2R+ cell numbers and promotes gland fission and carcinogenesis in response to the chemical carcinogen MNU. Pharmacological inhibition or genetic ablation of CCK2R attenuated progastrin-dependent stem cell expansion and carcinogenesis.
conclusionsCCK2R labels +4 antral stem cells that can be activated and expanded by progastrin, thus identifying one hormonal trigger for gastric stem cell interconversion and a potential target for gastric cancer chemoprevention and therapy.
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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.