ArticleProceedings of the National Academy of Sciences of the United States of America2012
CDX1 confers intestinal phenotype on gastric epithelial cells via induction of stemness-associated reprogramming factors SALL4 and KLF5.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 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
80 citing papers in PubMed, 131 citations in OpenAlex.
- Revisiting Pluripotency Acquisition: A Unified Framework for Reprogramming Strategies.Development, growth & differentiation · 2026Review
- Integrative transcriptomic analysis unveils FXR as a key regulator of intestinal stemness and inflammation in ulcerative colitis.International journal of molecular medicine · 2026Article
- Gastric Cancer: Pathobiology and Therapeutics.MedComm · 2026Review
- The mechanical niche in gastric precancer: extracellular matrix remodeling, mechanotransduction, and stem-cell fate.Frontiers in cell and developmental biology · 2026Review
- Divergent roles of DNA methylation, TRIM28, and p53 surveillance in human embryonic and trophoblast stem cells.bioRxiv : the preprint server for biology · 2025Article
- Helicobacter pylori-induced aberrant methylation of ID4 mediated by DNMT3B drives gastric cancer progression via DEC1-SHH signaling pathway.Cell death & disease · 2025Article
- Genetically engineered mouse models in gastric precancerous lesions research.World journal of gastrointestinal surgery · 2025Review
- The plasticity of epithelial cells and its potential in the induced differentiation of gastric cancer.Cell death discovery · 2024Review
- Endoscopic and Histological Gastritis in University Students with Helicobacter pylori Infection.Internal medicine (Tokyo, Japan) · 2024Article
- PHF10 inhibits gastric epithelium differentiation and induces gastric cancer carcinogenesis.Cancer gene therapy · 2024Article
- The role of gastric mucins and mucin-related glycans in gastric cancers.Cancer science · 2024Review
- HNF4A-Bridging the Gap Between Intestinal Metaplasia and Gastric Cancer.Evolutionary bioinformatics online · 2024Article
- The cryptic role of CXCL17/CXCR8 axis in the pathogenesis of cancers: a review of the latest evidence.Journal of cell communication and signaling · 2023Review
- High-Salt Diet ExacerbatesJournal of personalized medicine · 2023Review
- The Roles of Innate Lymphoid Cells in the Gastric Mucosal Immunology and Oncogenesis of Gastric Cancer.International journal of molecular sciences · 2023Review
- Oxidative-Stress-Mediated ER Stress Is Involved in Regulating Manoalide-Induced Antiproliferation in Oral Cancer Cells.International journal of molecular sciences · 2023Article
- The role of bile acid in intestinal metaplasia.Frontiers in physiology · 2023Review
- A transcriptional network of cell cycle dysregulation in noninvasive papillary urothelial carcinoma.Scientific reports · 2022Article
- scRNA-seq of gastric tumor shows complex intercellular interaction with an alternative T cell exhaustion trajectory.Nature communications · 2022Article
- Review
20 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intestinal metaplasia of the stomach, a mucosal change characterized by the conversion of gastric epithelium into an intestinal phenotype, is a precancerous lesion from which intestinal-type gastric adenocarcinoma arises. Chronic infection with Helicobacter pylori is a major cause of gastric intestinal metaplasia, and aberrant induction by H. pylori of the intestine-specific caudal-related homeobox (CDX) transcription factors, CDX1 and CDX2, plays a key role in this metaplastic change. As such, a critical issue arises as to how these factors govern the cell- and tissue-type switching. In this study, we explored genes directly activated by CDX1 in gastric epithelial cells and identified stemness-associated reprogramming factors SALL4 and KLF5. Indeed, SALL4 and KLF5 were aberrantly expressed in the CDX1(+) intestinal metaplasia of the stomach in both humans and mice. In cultured gastric epithelial cells, sustained expression of CDX1 gave rise to the induction of early intestinal-stemness markers, followed by the expression of intestinal-differentiation markers. Furthermore, the induction of these markers was suppressed by inhibiting either SALL4 or KLF5 expression, indicating that CDX1-induced SALL4 and KLF5 converted gastric epithelial cells into tissue stem-like progenitor cells, which then transdifferentiated into intestinal epithelial cells. Our study places the stemness-related reprogramming factors as critical components of CDX1-directed transcriptional circuitries that promote intestinal metaplasia. Requirement of a transit through dedifferentiated stem/progenitor-like cells, which share properties in common with cancer stem cells, may underlie predisposition of intestinal metaplasia to neoplastic transformation.
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.