E-cadherin modulates Wnt-dependent transcription in colorectal cancer cells but does not alter Wnt-independent gene expression in fibroblasts

Exp Cell Res. 2006 Feb 15;312(4):457-67. doi: 10.1016/j.yexcr.2005.11.007.


E-cadherin mediates homophilic adhesion of epithelial cells and is a major determinant of epithelial differentiation during embryonic development and tumor progression. At cell junctions, E-cadherin associates with beta-catenin, which also functions as a transcriptional co-activator of the canonical Wnt signaling pathway by interacting with TCF transcription factors. Here, we have analyzed whether E-cadherin plays a role in the control of gene expression in Wnt-dependent and -independent cellular systems. In DLD-1 colorectal cancer cells, which show constitutive activation of Wnt signaling and exhibit E-cadherin-based cell contacts, the siRNA-mediated knock-down of E-cadherin led to the disturbance of cell junctions, translocation of beta-catenin to the nucleus and an enhancement of beta-catenin/TCF-dependent reporter activity. In L929 fibroblasts, which are deficient in Wnt signaling and E-cadherin-mediated cell adhesion, ectopic expression of E-cadherin induced the stabilization of beta-catenin at the cell junctions and caused marked alterations in cellular morphology and phenotype. However, E-cadherin did not significantly change the transcriptional program of these cells as revealed by DNA microarray analysis. Our data indicate that E-cadherin may modulate Wnt-dependent gene expression by regulating the availability of beta-catenin but has a surprisingly small impact on gene expression in the absence of Wnt signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cadherins / physiology*
  • Cell Line, Tumor
  • Cell Membrane / metabolism
  • Cell Movement / genetics
  • Cell Nucleus / metabolism
  • Cell Shape / genetics
  • Colforsin / pharmacology
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology
  • Cytoskeleton / drug effects
  • Cytoskeleton / metabolism
  • Doxycycline / pharmacology
  • Fibroblasts / cytology
  • Fibroblasts / metabolism*
  • Gene Expression / genetics
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Keratinocytes / cytology
  • Keratinocytes / metabolism
  • Mice
  • Oligonucleotide Array Sequence Analysis
  • Protein Transport / genetics
  • RNA, Small Interfering / genetics
  • Tight Junctions / metabolism
  • Transcription, Genetic / drug effects
  • Transcription, Genetic / genetics
  • Transfection
  • Wnt Proteins / physiology*
  • beta Catenin / metabolism


  • Cadherins
  • RNA, Small Interfering
  • Wnt Proteins
  • beta Catenin
  • Colforsin
  • Doxycycline