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

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 coactivator of the canonical Writ 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 Writ-dependent and -independent cellular systems. In DLD-1 colorectal cancer cells, which show constitutive activation of Writ 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 Writ 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 Writ signaling. (C) 2005 Elsevier Inc. All rights reserved.