ArticleThe American journal of pathology2012
Methylation-dependent activation of CDX1 through NF-κB: a link from inflammation to intestinal metaplasia in the human stomach.
Article in The American journal of pathology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 27 citations in OpenAlex.
- [Identification of potential pathogenic genes of intestinal metaplasia based on transcriptomic sequencing and bioinformatics analysis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- The immune microenvironment in gastric adenocarcinoma.Nature reviews. Gastroenterology & hepatology · 2022Review
- Gastric epithelial histology and precancerous conditions.World journal of gastrointestinal oncology · 2022Review
- Caudal type homeoboxes as a driving force inGut microbes · 2020Article
- IL-32 gamma reduces lung tumor development through upregulation of TIMP-3 overexpression and hypomethylation.Cell death & disease · 2018Article
- hTERT promotes gastric intestinal metaplasia by upregulating CDX2 via NF-κB signaling pathway.Oncotarget · 2017Article
- Chronic Kidney Disease Induces Inflammatory CD40+ Monocyte Differentiation via Homocysteine Elevation and DNA Hypomethylation.Circulation research · 2016Article
- [Pathogenetic aspects in precursor lesions of gastrointestinal tumors].Der Pathologe · 2016Review
- Epigenetic modifications and NF-κB pathway activity in Cu,Zn-SOD-deficient mice.Molecular and cellular biochemistry · 2014Article
- Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer.Nature genetics · 2014Article
- Large deletions encompassing the TCOF1 and CAMK2A genes are responsible for Treacher Collins syndrome with intellectual disability.European journal of human genetics : EJHG · 2014Article
- Synbindin in extracellular signal-regulated protein kinase spatial regulation and gastric cancer aggressiveness.Journal of the National Cancer Institute · 2013Article
- Death-associated protein kinase controls STAT3 activity in intestinal epithelial cells.The American journal of pathology · 2013Article
- Quantitative leukocyte BDNF promoter methylation analysis in bipolar disorder.International journal of bipolar disorders · 2013Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
Abstract
The caudal homeobox factor 1 (CDX1) is an essential transcription factor for intestinal differentiation. Its aberrant expression in intestinal metaplasia of the upper gastrointestinal tract is a hallmark within the gastritis-metaplasia-carcinoma sequence. CDX1 expression is influenced by certain pathways, such as Wnt, Ras, or NF-κB signaling; however, these pathways alone cannot explain the transient expression of CDX1 in intestinal metaplasia or the molecular inactivation mechanism of its loss in cases of advanced gastric cancer. In this study, we investigated the epigenetic inactivation of CDX1 by promoter methylation, as well as the functional link of CDX1 promoter methylation to the inflammatory NF-κB signaling pathway. We identified methylation-dependent NF-κB binding to the CDX1 promoter and quantified it using competitive electrophoretic mobility shift assays and chromatin immunoprecipitation. A methylated CDX1 promoter was associated with closed chromatin structure, reduced NF-κB binding, and transcriptional silencing. Along the gastritis-metaplasia-carcinoma sequence, we observed a biphasic pattern of tumor necrosis factor-α (TNF-α) protein expression and an inverse biphasic pattern of CDX1 promoter methylation; both are highly consistent with CDX1 protein expression. The stages of hyper-, hypo-, and hyper-methylation patterns of the CDX1 promoter were inversely correlated with the NF-κB signaling activity along this sequence. In conclusion, these functionally interacting events drive CDX1 expression and contribute to intestinal metaplasia, epithelial dedifferentiation, and carcinogenesis in the human stomach.
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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.