Mutated E-Cadherin: Genomic and Functional Characterization in Thyroid Cells from the KAT Family

Abstract

Members of a family of thyroid cell lines (KAT) were analyzed because they expressed a higher molecular weight (135 kd) form of E-cadherin at their surface. We found that this aberrant E-cadherin is the result of a point mutation in the exon 9 donor splice site causing a skipping of exon 9 with consequent deletion of the corresponding aminoacids on E-cadherin protein. As a spin-off, we report that the various members of the KAT family share this mutation as well as the genetic background. Furthermore we found that this mutated protein leads to disturbed cell-cell adhesion although E-cadherin is still able to mediate the formation of the cadherin/ catenin complex. We also demonstrate the presence of another cell–cell adhesion complex, formed by Pcadherin and the catenins. The latter is also not able to mediate cell–cell adhesion. Although these cells lack cell–cell adhesion they are not invasive without exogenous stimulus.