The role of Cdx proteins in intestinal development and cancer

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.

Helicobacter pylori CagA interacts with E-cadherin and deregulates the β-catenin signal that promotes intestinal transdifferentiation in gastric epithelial cells

“…One of those CagA-activated genes is cdx1, which encodes CDX1 transcription factor (Lickert et al, 2000). CDX1 and CDX2 are specifically expressed in the intestine, where they play a crucial role in the regulation of cell proliferation and differentiation (Guo et al, 2004). Aberrant expression of CDX1 is found in areas of the stomach and esophagus containing intestinal metaplasia (Silberg et al, 1997) and transgenic expression of CDX1 in mouse stomach induces intestinal metaplasia (Mutoh et al, 2004).…”

Hepatocyte nuclear factor-4α promotes differentiation of intestinal epithelial cells in a coculture system

“…Total RNA was isolated from cultured cells and subjected to a DNase treatment according to the manufacturer's instructions (Totally RNA kit). Reverse transcriptions were carried out at 42°C for 1 h in the presence of 2 g RNA, 40 mU of polyoligo(dT) [12][13][14][15][16][17][18], and 40 U of Reverse Transcriptase (Roche Diagnostics). Semiquantitative PCR was performed in a total volume of 20 l in the presence of 1 l of RT reaction, 0.6 U of Taq DNA polymerase (New England Biolabs), 0.2 mM dNTPs, and 30 ng of each specific primer.…”

Repression of the Desmocollin 2 Gene Expression in Human Colon Cancer Cells Is Relieved by the Homeodomain Transcription Factors Cdx1 and Cdx2

“…Is it by activating transcription or disrupting a repressor complex? Typically, Cdx1 and Cdx2 act as activators of transcription, binding proximal promoter regions to enhance promoter activity (10). However, the Cdx2-responsive elements in the DSC2 promoter are quite distant from the transcription initiation site of the gene.…”

“…However, little is known about the mechanisms regulating DSC2 gene expression in this tissue. The homeobox transcription factors Cdx1 and Cdx2 are important regulators of intestinal epithelial cell differentiation, cell adhesion and columnar morphology, apoptosis, and proliferation (10). They modulate these diverse processes largely by enhancing the expression of several target genes, including sucrase isomaltase, haephestin, LI-cadherin, claudin2, Bcl2, and KLF4 (11-16).…”