Expression of Eph receptors and ephrins is differentially regulated by E-cadherin

E-cadherin is the main cell adhesion molecule of early embryonic and adult epithelial cells. Downregulation of E-cadherin is associated with epithelia l-mesenchymal transition during embryonic mesoderm formation and tumor prog ression. To identify genes whose expression is affected by the loss of E-ca dherin, we compared mRNA expression patterns between wild-type and E-cadher in null mutant embryonic stem (ES) cells. We found that expression of sever al Eph receptors and ephrins is dependent on E-cadherin. Rescue of E-cadher in null ES cells with E-cadherin cDNA restores the wild-type expression pat tern of Eph family members. Rescue of E-cadherin null ES cells with N-cadhe rin cDNA does not restore the wild-type expression pattern, indicating that the regulation of differential expression of Eph family members is specifi c to E-cadherin, Constitutive ectopic expression of E-cadherin in non-epith elial NIH3T3 cells results in the production of the EphA2 receptor. In epit helial cells, E-cadherin is required for EphA2 receptor localization at cel l-cell contacts; in the absence of functional E-cadherin, EphA2 localizes t o the perinuclear region. Our results indicate that E-cadherin mag be direc tly or indirectly required for the membrane localization of Eph receptors a nd their membrane-bound ligands.