ArticleThe Journal of clinical investigation2009
Inactivating cholecystokinin-2 receptor inhibits progastrin-dependent colonic crypt fission, proliferation, and colorectal cancer in mice.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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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.
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Who cites it
53 citing papers in PubMed, 87 citations in OpenAlex.
- Progastrin Promotes Colorectal Cancer Stem Cell-Like Properties via the Receptor PZR.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Gut Hormones and Inflammatory Bowel Disease.Biomolecules · 2025Review
- Deciphering Aflatoxin B1 affected critical molecular pathways governing cancer: A bioinformatics study using CTD and PANTHER databases.Mycotoxin research · 2025Article
- Intestinal Gastrin/CCKBR (Cholecystokinin B Receptor) Ameliorates Salt-Sensitive Hypertension by Inhibiting Intestinal NaHypertension (Dallas, Tex. : 1979) · 2022Article
- An update on the biological characteristics and functions of tuft cells in the gut.Frontiers in cell and developmental biology · 2022Review
- Review
- Notch signaling drives development of Barrett's metaplasia from Dclk1-positive epithelial tuft cells in the murine gastric mucosa.Scientific reports · 2021Article
- Cholecystokinin type 2 receptor in colorectal cancer: diagnostic and therapeutic target.Journal of cancer research and clinical oncology · 2020Article
- Notch Signaling Mediates Differentiation in Barrett's Esophagus and Promotes Progression to Adenocarcinoma.Gastroenterology · 2020Observational
- Hormonal Suppression of Stem Cells Inhibits Symmetric Cell Division and Gastric Tumorigenesis.Cell stem cell · 2020Article
- Targeting cholecystokinin-2 receptor for pancreatic cancer chemoprevention.Molecular carcinogenesis · 2019Article
- The role of GαBiochemistry and biophysics reports · 2018Article
- The Activation and Signaling Mechanisms of GPR56/ADGRG1 in Melanoma Cell.Frontiers in oncology · 2018Review
- Cell cycle dependent expression of the CCK2 receptor by gastrointestinal myofibroblasts: putative role in determining cell migration.Physiological reports · 2017Article
- Article
- The G-protein coupled receptor 56, expressed in colonic stem and cancer cells, binds progastrin to promote proliferation and carcinogenesis.Oncotarget · 2017Article
- Activation of the mTOR Pathway by Oxaliplatin in the Treatment of Colorectal Cancer Liver Metastasis.PloS one · 2017Article
- Gastrin attenuates ischemia-reperfusion-induced intestinal injury in rats.Experimental biology and medicine (Maywood, N.J.) · 2016Article
- The role of the calcium-sensing receptor in gastrointestinal inflammation.Seminars in cell & developmental biology · 2016Review
- Epigenetic regulation of humanStem cell investigation · 2016Article
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12 authors at 3 institutions in 3 countries.
Funding
Abstract
Hyperproliferation of the colonic epithelium, leading to expansion of colonic crypt progenitors, is a recognized risk factor for colorectal cancer. Overexpression of progastrin, a nonamidated and incompletely processed product of the gastrin gene, has been shown to induce colonic hyperproliferation and promote colorectal cancer in mice, but the mechanism of pathogenesis has not been defined. Cholecystokinin-2 receptor (CCK2R) is the primary receptor for cholecystokinin (CCK) and amidated gastrin. Here, we show that Cck2r was expressed in murine colonic crypts and upregulated in the transgenic mice that overexpress human progastrin. Murine deletion of Cck2r abrogated progastrin-dependent increases in colonic proliferation, mucosal thickness, and beta-catenin and CD44 expression in the colon tumor. In addition, either deletion or antagonism of Cck2r resulted in the inhibition of progastrin-dependent increases in progenitors expressing doublecortin and CaM kinase-like-1 (DCAMKL1), stem cells expressing leucine rich repeat-containing G protein-coupled receptor 5 (LgR5), and colonic crypt fission. Furthermore, in the azoxymethane mouse model of colorectal carcinogenesis, Cck2r deletion in human progastrin-overexpressing mice resulted in markedly decreased aberrant crypt foci formation and substantially reduced tumor size and multiplicity. Taken together, these observations indicate that progastrin induces proliferative effects, primarily in colonic progenitor cells, through a CCK2R-dependent pathway. Moreover, our data suggest that CCK2R may be a potential target in the treatment or prevention of colorectal cancer.
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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.