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 epithelial-mesenchymal transition during embryonic mesoderm formation and tumor progression. To identify genes whose expression is affected by the loss of E-cadherin, we compared mRNA expression patterns between wild-type and E-cadherin null mutant embryonic stem (ES) cells. We found that expression of several Eph receptors and ephrins is dependent on E-cadherin. Rescue of E-cadherin null ES cells with E-cadherin cDNA restores the wild-type expression pattern of Eph family members. Rescue of E-cadherin null ES cells with N-cadherin cDNA does not restore the wild-type expression pattern, indicating that the regulation of differential expression of Eph family members is specific to E-cadherin. Constitutive ectopic expression of E-cadherin in non-epithelial NIH3T3 cells results in the production of the EphA2 receptor. In epithelial cells, E-cadherin is required for EphA2 receptor localization at cell-cell contacts; in the absence of functional E-cadherin, EphA2 localizes to the perinuclear region. Our results indicate that E-cadherin may be directly or indirectly required for the membrane localization of Eph receptors and their membrane-bound ligands.
Orsulic
S
S
Max-Planck-Institut für Immunbiologie, Stübeweg 51, D-79108 Freiburg, Germany. sorsulic@nhgri.nih.gov
Kemler
R
R
D015820:Cadherins / Q000235:genetics* / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology*; D002449:Cell Aggregation / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D036383:Ephrin-A2; D004847:Epithelial Cells / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic
D015820:Cadherins; D036383:Ephrin-A2; D012333:RNA, Messenger; D014157:Transcription Factors