E-cadherin regulates the stability and transcriptional activity of β-catenin in embryonic stem cells
E-CADHERIN is abundantly expressed in embryonic stem cells (ESCs) and plays an important role in the maintenance of cell-cell adhesions. However, the exact function of this molecule beyond cell adhesion, in the context of cell fate decisions is largely unknown. Using mouse ESCs (mESCs), we demonstrate that E-CADHERIN and β-CATENIN interact at the membrane and continue to do so upon internalization within the cell. Knockout of the gene encoding E-CADHERIN, Cdh1, in mESCs resulted in a failure to form tight colonies, accompanied by altered expression of differentiation markers, and retention of pluripotency factor expression during differentiation. Interestingly, Cdh1-/- mESCs showed a dramatic reduction in β-CATENIN levels. Transcriptional profiling of Cdh1-/- mESCs displayed a significant alteration in the expression of a subset of β-CATENIN targets, in a cell-state dependent manner. While treatment with a pharmacological inhibitor against GSK3β could rescue levels of β-CATENIN in Cdh1-/- mESCs, expression of downstream targets were altered in a context-dependent manner, indicating an additional layer of regulation within this subset. Together, our results reveal the existence of a cell-state-dependent regulation of β-CATENIN and its transcriptional targets in an E-CADHERIN dependent manner. Our findings hint at hitherto unknown roles played by E-CADHERIN in regulating the activity of β-CATENIN in ESCs.