The role of CDX2 in Caco-2 cell differentiation

Eur J Pharm Biopharm. 2013 Sep;85(1):20-5. doi: 10.1016/j.ejpb.2013.03.018.

Abstract

Background: CDX2 plays a key part in the differentiation of Caco-2 cells, a colon carcinoma derived cell line that undergoes spontaneous differentiation. The effect of CDX2 expression in Caco-2 cells over time in culture has not been studied yet on a genome-wide level.

Methods: The impact of CDX2 expression on the genomic profile of Caco-2 cells was studied by transducing cells with CDX2 targeting shRNAs. Knockdown efficiency was assessed on mRNA level and protein level by RTPCR, microarrays, and Western blots. Gene set enrichment analysis was performed to assess regulation of specific gene sets.

Results: CDX2 expression had an inhibitory effect on the transcriptional activity of β-catenin/TCF at early stages of culturing, while at later stages, its role in the trans-activation of target genes specific for small intestinal enterocytes seemed more dominant.

Conclusions: The unique induction of a small intestinal signature upon differentiation in Caco-2 cells seems to be at least partially under the control of CDX2.

Keywords: CDX2; Caco-2 cells; Differentiation; Genomic profiling; Intestine; Wnt pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CDX2 Transcription Factor
  • Caco-2 Cells
  • Cell Differentiation*
  • Chemotaxis
  • Databases, Genetic
  • Down-Regulation*
  • Enterocytes / cytology*
  • Enterocytes / metabolism
  • Gene Expression Profiling
  • Genomics / methods
  • Homeodomain Proteins / antagonists & inhibitors
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Humans
  • Kinetics
  • RNA Interference
  • RNA, Messenger / metabolism
  • RNA, Small Interfering
  • TCF Transcription Factors / antagonists & inhibitors
  • TCF Transcription Factors / genetics
  • TCF Transcription Factors / metabolism
  • Transcriptional Activation*
  • Up-Regulation*
  • Wnt Signaling Pathway*
  • beta Catenin / antagonists & inhibitors
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • CDX2 Transcription Factor
  • CDX2 protein, human
  • CTNNB1 protein, human
  • Homeodomain Proteins
  • RNA, Messenger
  • RNA, Small Interfering
  • TCF Transcription Factors
  • beta Catenin