ArticleGut2011
CDX2 autoregulation in human intestinal metaplasia of the stomach: impact on the stability of the phenotype.
Article in Gut, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 58 citations in OpenAlex.
- Helicobacter pylori SlyD stabilizes TPT1 via hnRNPK and enhances OCT1-mediated CDX2 transcriptional activation to drive gastric intestinal metaplasia.BMC medicine · 2025Article
- The Killer's Web: Interconnection between Inflammation, Epigenetics and Nutrition in Cancer.International journal of molecular sciences · 2024Review
- Inference on autoregulation in gene expression with variance-to-mean ratio.Journal of mathematical biology · 2023Article
- Epigenetics as a mediator of plasticity in cancer.Science (New York, N.Y.) · 2023Review
- Morphogen Signals Shaping the Gastric Glands in Health and Disease.International journal of molecular sciences · 2022Review
- Transcription factor-mediated intestinal metaplasia and the role of a shadow enhancer.Genes & development · 2022Article
- Silencing LINC01021 inhibits gastric cancer through upregulation of KISS1 expression by blocking CDK2-dependent phosphorylation of CDX2.Molecular therapy. Nucleic acids · 2021Article
- Chromatin regulatory dynamics of early human small intestinal development using a directed differentiation model.Nucleic acids research · 2021Article
- Caudal type homeoboxes as a driving force inGut microbes · 2020Article
- A panel of intestinal differentiation markers (CDX2, GPA33, and LI-cadherin) identifies gastric cancer patients with favourable prognosis.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2020Article
- TGR5-HNF4α axis contributes to bile acid-induced gastric intestinal metaplasia markers expression.Cell death discovery · 2020Article
- Activation of FXR promotes intestinal metaplasia of gastric cells via SHP-dependent upregulation of the expression of CDX2.Oncology letters · 2018Article
- R-spondin1/Wnt-enhanced Ascl2 autoregulation controls the self-renewal of colorectal cancer progenitor cells.Cell cycle (Georgetown, Tex.) · 2018Article
- HpSlyD inducing CDX2 and VIL1 expression mediated through TCTP protein may contribute to intestinal metaplasia in the stomach.Scientific reports · 2017Article
- hTERT promotes gastric intestinal metaplasia by upregulating CDX2 via NF-κB signaling pathway.Oncotarget · 2017Article
- Helicobacter pylori-induced gastric pathology: insights from in vivo and ex vivo models.Disease models & mechanisms · 2017Review
- Inhibition of CDH17 gene expression via RNA interference reduces proliferation and apoptosis of human MKN28 gastric cancer cells.International journal of oncology · 2017Article
- CDX2 immunostaining in primary and metastatic germ cell tumours of the testis.The Journal of international medical research · 2016Article
- CDX2 homeoprotein is involved in the regulation of ST6GalNAc-I gene in intestinal metaplasia.Laboratory investigation; a journal of technical methods and pathology · 2015Article
- Review
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimsIntestinal metaplasia (IM) is a gastric preneoplastic lesion that appears following Helicobacter pylori infection and confers an increased risk for development of cancer. It is induced by gastric expression of the intestine-specific transcription factor CDX2. The regulatory mechanisms involved in triggering and maintaining gastric CDX2 expression have not been fully elucidated. The Cdx2(+/-) mouse develops intestinal polyps with gastric differentiation and total loss of Cdx2 expression in the absence of structural loss of the second allele, suggesting a regulatory defect. This putative haplo-insufficiency, together with the apparent stability of IM, led to the hypothesis that CDX2 regulates its own expression through an autoregulatory loop in both contexts.
methodsGastrointestinal cell lines were co-transfected with wild-type or mutated Cdx2 promoter constructs and CDX2 expression vector for luciferase assays. Transfection experiments were also used to assess endogenous CDX2 autoregulation, evaluated by RT-PCR, qPCR and western blotting. Chromatin immunoprecipitation was performed in a cell line, mouse ileum and human IM.
resultsCDX2 binds to and transactivates its own promoter and positively regulates its expression in gastrointestinal human carcinoma cell lines. Furthermore, CDX2 is bound to its promoter in the mouse ileum and in human gastric IM, providing a major contribution to understanding the relevance of this autoregulatory pathway in vivo.
conclusionThe results of this study demonstrate another layer of complexity in CDX2 regulation by an effective autoregulatory loop which may have a major impact on the stability of human IM, possibly resulting in the inevitable progression of the gastric carcinogenesis pathway.
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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.