ArticleGastroenterology2013
Progastrin stimulates colonic cell proliferation via CCK2R- and β-arrestin-dependent suppression of BMP2.
Article in Gastroenterology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 41 citations in OpenAlex.
- Progastrin Promotes Colorectal Cancer Stem Cell-Like Properties via the Receptor PZR.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Expression of bone morphogenetic protein signaling pathway players in the jejunum and colon of adult rats.European journal of histochemistry : EJH · 2025Article
- SOX9 Modulates the Transformation of Gastric Stem Cells Through Biased Symmetric Cell Division.Gastroenterology · 2023Article
- Cysteine protease of Clonorchis sinensis alleviates DSS-induced colitis in mice.PLoS neglected tropical diseases · 2022Article
- Intestinal Gastrin/CCKBR (Cholecystokinin B Receptor) Ameliorates Salt-Sensitive Hypertension by Inhibiting Intestinal NaHypertension (Dallas, Tex. : 1979) · 2022Article
- Review
- Cholecystokinin type 2 receptor in colorectal cancer: diagnostic and therapeutic target.Journal of cancer research and clinical oncology · 2020Article
- Hormonal Suppression of Stem Cells Inhibits Symmetric Cell Division and Gastric Tumorigenesis.Cell stem cell · 2020Article
- New Routes in GPCR/β-Arrestin-Driven Signaling in Cancer Progression and Metastasis.Frontiers in pharmacology · 2019Review
- The Activation and Signaling Mechanisms of GPR56/ADGRG1 in Melanoma Cell.Frontiers in oncology · 2018Review
- The G-protein coupled receptor 56, expressed in colonic stem and cancer cells, binds progastrin to promote proliferation and carcinogenesis.Oncotarget · 2017Article
- β-arrestin1 at the cross-road of endothelin-1 signaling in cancer.Journal of experimental & clinical cancer research : CR · 2016Review
- Article
- Gastrin attenuates ischemia-reperfusion-induced intestinal injury in rats.Experimental biology and medicine (Maywood, N.J.) · 2016Article
- Adipocytes promote prostate cancer stem cell self-renewal through amplification of the cholecystokinin autocrine loop.Oncotarget · 2016Article
- MiR-148a Functions as a Tumor Suppressor by Targeting CCK-BR via Inactivating STAT3 and Akt in Human Gastric Cancer.PloS one · 2016Article
- Cancer stem cells in human digestive tract malignancies.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
- Gastric Hypersecretory States: Investigation and Management.Current treatment options in gastroenterology · 2015Article
- Progastrin a new pro-angiogenic factor in colorectal cancer.Oncogene · 2015Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND &
aimsProgastrin stimulates colonic mucosal proliferation and carcinogenesis through the cholecystokinin 2 receptor (CCK2R)-partly by increasing the number of colonic progenitor cells. However, little is known about the mechanisms by which progastrin stimulates colonic cell proliferation. We investigated the role of bone morphogenetic proteins (BMPs) in progastrin induction of colonic cell proliferation via CCK2R.
methodsWe performed microarray analysis to compare changes in gene expression in the colonic mucosa of mice that express a human progastrin transgene, gastrin knockout mice, and C57BL/6 mice (controls); the effects of progastrin were also determined on in vitro colonic crypt cultures from cholecystokinin 2 receptor knockout and wild-type mice. Human colorectal and gastric cancer cells that expressed CCK2R were incubated with progastrin or Bmp2; levels of β-arrestin 1 and 2 were knocked down using small interfering RNAs. Cells were analyzed for progastrin binding, proliferation, changes in gene expression, and symmetric cell division.
resultsThe BMP pathway was down-regulated in the colons of human progastrin mice compared with controls. Progastrin suppressed transcription of Bmp2 through a pathway that required CCK2R and was mediated by β-arrestin 1 and 2. In mouse colonic epithelial cells, down-regulation of Bmp2 led to decreased phosphorylation of Smads1/5/8 and suppression of inhibitor of DNA binding 4. In human gastric and colorectal cancer cell lines, CCK2R was necessary and sufficient for progastrin binding and induction of proliferation; these effects were blocked when cells were incubated with recombinant Bmp2. Incubation with progastrin increased the number of CD44(+), bromodeoxyuridine+, and NUMB(+) cells, indicating an increase in symmetric divisions of putative cancer stem cells.
conclusionsProgastrin stimulates proliferation in colons of mice and cultured human cells via CCK2R- and β-arrestin 1 and 2-dependent suppression of Bmp2 signaling. This process promotes symmetric cell division.
Indexed as
Identifiers
What OpenQuestion holds
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.