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beta-Catenin is essential for E-cadherin-mediated cell adhesion in epithelial cells, but it also forms nuclear complexes with high mobility group transcription factors. Using a mouse mammary epithelial cell system, we have shown previously that conversion of epithelial cells to a fibroblastoid phenotype (epithelial-mesenchymal transition) involves downregulation of E-cadherin and upregulation of beta-catenin transcriptional activity. Here, we demonstrate that transient expression of exogenous E-cadherin in both epithelial and fibroblastoid cells arrested cell growth or caused apoptosis, depending on the cellular E-cadherin levels. By expressing E-cadherin subdomains, we show that the growth-suppressive effect of E-cadherin required the presence of its cytoplasmic beta-catenin interaction domain and/or correlated strictly with the ability to negatively interfere with beta-catenin transcriptional activity. Furthermore, coexpression of beta-catenin or lymphoid enhancer binding factor-1 or T cell factor 3 with E-cadherin rescued beta-catenin transcriptional activity and counteracted E-cadherin-mediated cell cycle arrest. Stable expression of E-cadherin in fibroblastoid cells decreased beta-catenin activity and reduced cell growth. Since proliferating cells had a higher beta-catenin activity than G1 phase-arrested or contact-inhibited cells, we conclude that beta-catenin transcriptional activity is essential for cell proliferation and can be controlled by E-cadherin in a cell adhesion-independent manner.
Stockinger et al. (Mon,) studied this question.