We believe that the only exception to the requirement for p120 occurs in cells that express p120 family members such as ARVCF or δ-catenin. This qualifier is based in part on cell lines such as HCT116 where the observed reduction in E-cadherin levels after p120 siRNA expression did not perfectly parallel the extent of p120 loss. Indeed, although ARVCF is typically difficult to detect in many epithelial cell lines, it is expressed at moderate levels in HCT116 cells (unpublished data). Our data show that ARVCF and δ-catenin efficiently compensate for p120 loss when ectopically expressed in A431 cell lines expressing p120 siRNA. Despite significant structural and sequence similarity, plakophilin-3 had no effect, presumably because it does not bind classical cadherins. These data strongly imply that surface cadherin stability is invariably dependent on the binding of either p120 or a closely related family member, and the presence of variable levels of p120 family members likely accounts for the discrepancy in cell lines where p120 knockdown does not cause a corresponding loss of resident classical cadherins.
