The role of Cdx proteins in intestinal development and cancer.
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TLDR
Current understanding of the roles of the caudal homologues Cdx1 and Cdx2 in intestinal development and carcinogenesis is explored.Abstract:
Since their original identification in Drosophila, the caudal related homologues (Cdx1 and Cdx2) have been known to be evolutionarily conserved both in molecular structure and function. In a great variety of organisms they are recognized to function critically during antero-posterior patterning and the development of the intestinal epithelium. The Cdx homologues, when expressed, modulate a diverse set of processes including proliferation, apoptosis, cell-adhesion, and columnar morphology. They are also necessary for the expression of an increasing number of intestine-specific genes. By targeting these processes and genes, the Cdx homologues promote the appearance of a mature intestinal cell phenotype. In addition to these critical roles during development, accumulating evidence suggests that the Cdx homologues may play significant roles in oncogenesis in the gastrointestinal tract and other tissues. In the colon, several studies suggest the Cdx homologues may act as tumor suppressors. However, ectopic Cdx1 and Cdx2 expression is involved in the development of the precancerous intestinal metaplasia in the stomach and esophagus, and may be a transforming event in one form of acute myelogenous leukemia. This review will explore our current understanding of the roles of the caudal homologues Cdx1 and Cdx2 in intestinal development and carcinogenesis.read more
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Helicobacter pylori CagA interacts with E-cadherin and deregulates the β-catenin signal that promotes intestinal transdifferentiation in gastric epithelial cells
Naoko Murata-Kamiya,Yo Kurashima,Yasuhiro Teishikata,Y Yamahashi,Y. Saito,Hideaki Higashi,Hiroyuki Aburatani,Tetsu Akiyama,Richard M. Peek,Takeshi Azuma,Masanori Hatakeyama +10 more
TL;DR: Results indicate that perturbation of the E-cadherin/β-catenin complex by H. pylori CagA plays an important role in the development of intestinal metaplasia, a premalignant transdifferentiation of gastric epithelial cells from which intestinal-type gastric adenocarcinoma arises.
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Differentiation-Specific Histone Modifications Reveal Dynamic Chromatin Interactions and Partners for the Intestinal Transcription Factor CDX2
Michael P. Verzi,Hyunjin Shin,Housheng Hansen He,Rita Sulahian,Rita Sulahian,Clifford A. Meyer,Robert K. Montgomery,Robert K. Montgomery,James C. Fleet,Myles Brown,Myles Brown,X. Shirley Liu,Ramesh A. Shivdasani,Ramesh A. Shivdasani +13 more
TL;DR: Dynamic CDX2 occupancy corresponds with condition-specific gene expression and to differential co-occupancy with other tissue-restricted transcription factors, such as GATA6 and HNF4A, and reveals dynamic, context-specific functions and mechanisms of a prominent transcriptional regulator within a cell lineage.
Journal ArticleDOI
Acid, Bile, and CDX: the ABCs of making Barrett's metaplasia
TL;DR: The roles of developmental signaling pathways and the Cdx genes in the development of normal gut epithelia are reviewed and the potential mechanisms whereby GERD may induce the esophageal expression of C dx genes and other morphogenetic factors that mediate thedevelopment of Barrett's metaplasia are addressed.
Journal ArticleDOI
Regulation of Cdx2 expression by promoter methylation, and effects of Cdx2 transfection on morphology and gene expression of human esophageal epithelial cells
Tong Liu,Xinyan Zhang,Xinyan Zhang,Chi-Kwong So,Su Wang,Peng Wang,Liying Yan,Rene Myers,Zhigang Chen,Amy P. Patterson,Chung S. Yang,Xiaoxin Chen,Xiaoxin Chen +12 more
TL;DR: It is suggested that exposure to acid and/or bile acids may activate Cdx2 expression in human esophageal epithelial cells through promoter demethylation, and ectopic Cdx 2 expression in esophagal squamous epithel cells may contribute to intestinal metaplasia of the esophagus.
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Transcription factors c-Myc and CDX2 mediate E-selectin ligand expression in colon cancer cells undergoing EGF/bFGF-induced epithelial–mesenchymal transition
TL;DR: A significant link between sLex/a expression and EMT in colon cancer cells and a pivotal role of c-Myc and CDX2 in regulating sLex /a expression during EMT are suggested.
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