Transactivation of Vimentin by -Catenin in Human Breast Cancer Cells

The cytoplasmic and nuclear redistribution of -catenin and the de novo expression of vimentin are frequently involved in the epithelial-tomesenchymal transition associated with increased invasive/migratory properties of epithelial cells. Because -catenin can act as a coactivator of transcription through its binding to the T-cell factor (TCF)/lymphoid enhancer factor 1 transcription factor family, we have explored the possibility that -catenin/TCF could directly transactivate vimentin. We first compared vimentin expression in relation with the localization of -catenin in eight breast cancer cell lines displaying various degrees of invasiveness and in a model of cell migration using human mammary MCF10A cells. We could thus show a cytoplasmic and/or nuclear distribution of -catenin in invasive/migratory cells expressing vimentin, but not in noninvasive/stationary vimentin-negative cell lines. In addition, the human vimentin promoter was found to be up-regulated by -catenin and TCF-4 cotransfection. Varying with the cellular background, a diminution of this up-regulation was observed when the putative -catenin/TCF binding site of the vimentin promoter was mutated. Our results therefore demonstrate that the vimentin promoter is a target of the -catenin/TCF pathway and strongly suggest an implication of this regulation in epithelial cell migration/invasion.