ArticleLaboratory investigation; a journal of technical methods and pathology2016
Bile acids induce Delta-like 1 expression via Cdx2-dependent pathway in the development of Barrett's esophagus.
Article in Laboratory investigation; a journal of technical methods and pathology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 24 citations in OpenAlex.
- CDX2 confers ferroptosis resistance in stage II-III colon cancer via upregulation of NUPR1.Cell death & disease · 2026Article
- GATA4 Forms a Positive Feedback Loop with CDX2 to Transactivate MUC2 in Bile Acids-Induced Gastric Intestinal Metaplasia.Gut and liver · 2024Article
- Review
- Signaling Pathways in the Pathogenesis of Barrett's Esophagus and Esophageal Adenocarcinoma.International journal of molecular sciences · 2023Review
- The role of bile acid in intestinal metaplasia.Frontiers in physiology · 2023Review
- Article
- Notch Signaling Mediates Differentiation in Barrett's Esophagus and Promotes Progression to Adenocarcinoma.Gastroenterology · 2020Observational
- Salivary Pepsin as an Intrinsic Marker for Diagnosis of Sub-types of Gastroesophageal Reflux Disease and Gastroesophageal Reflux Disease-related Disorders.Journal of neurogastroenterology and motility · 2020Article
- Bile acids promote gastric intestinal metaplasia by upregulating CDX2 and MUC2 expression via the FXR/NF-κB signalling pathway.International journal of oncology · 2019Article
- Gastroesophageal reflux and Barrett's esophagus: a pathway to esophageal adenocarcinoma.Updates in surgery · 2018Review
- Origins of Metaplasia in Barrett's Esophagus: Is this an Esophageal Stem or Progenitor Cell Disease?Digestive diseases and sciences · 2018Review
- Notch Signaling Pathway Is Inhibited in the Development of Barrett's Esophagus: An In Vivo and In Vitro Study.Canadian journal of gastroenterology & hepatology · 2018Article
- Longitudinal study of esophageal mucosal damage after esophagectomy and gastric interposition: relationship between reflux-related mucosal injury and Notch signaling.Journal of thoracic disease · 2017Article
- From Heartburn to Barrett's Esophagus, and Beyond.World journal of surgery · 2017Review
- Reflux esophagitis and its role in the pathogenesis of Barrett's metaplasia.Journal of gastroenterology · 2017Review
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Authors and funding
9 authors at 2 institutions in 2 countries.
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No grant is acknowledged in the PubMed record.
Abstract
Crosstalk between the Notch signaling pathway and Caudal-related homeobox 2 (Cdx2) has important roles in the development of Barrett's esophagus (BE). We investigated the expression and function of the Notch signaling ligand Delta-like 1 (Dll1) during the development of BE. We determined the expression levels of Dll1 and intracellular signaling molecules related to Notch signaling ((Notch1, Hairy/enhancer of split 1 (Hes1), and Atonal homolog 1 (ATOH1)) in human esophageal squamous and Barrett's epithelium samples. Next, those expression levels in esophageal squamous cells (Het-1A) and Barrett's esophageal cells (CP-A and BAR-T) following stimulation with either bile acids or gamma-secretase inhibitor were investigated. Finally, changes in those expression levels following transfection of a Cdx2 or Dll1 expression vector into Het-1A cells were examined. In addition, changes in those expression levels following knockdown of Cdx2 or Dll1 in CP-A cells were also examined. Dll1 was found to be upregulated and localized in the cell membrane and cytoplasm in BE. Bile acids enhanced cytoplasmic expression of Dll1 in CP-A cells, while cleaved Notch1 expression did not change, suggesting lack of a Dll1 agonistic effect on Notch signaling. Cells transfected with Cdx2 revealed significantly enhanced Dll1, while forced expression of Dll1 enhanced ATOH1, Cdx2, and MUC2 expression levels. Nevertheless, enhanced Dll1 did not induce Hes1 expression, suggesting that Dll1 may primarily function as an intracellular signaling molecule and not a Notch agonistic ligand in the canonical pathway. In addition, knockdown of Cdx2 completely abrogated any increase in Dll1 expression upon treatment with bile acids. Our results revealed a novel function of Dll1: facilitation of intestinal metaplasia in conjunction with Cdx2 expression. Furthermore, they suggest that intracellular induction of Dll1 expression in esophageal epithelial cells due to Cdx2 induction in response to bile acids has important roles in BE development.
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