Cadherin cytoplasmic domains inhibit the cell surface localization of endogenous E-cadherin, blocking desmosome and tight junction formation and inducing cell dissociation.

ABSTRACT: The downregulation of E-cadherin function has fundamental consequences with respect to cancer progression, and occurs as part of the epithelial-mesenchymal transition (EMT). In this study, we show that the expression of the Discosoma sp. red fluorescent protein (DsRed)-tagged cadherin cytoplasmic domain in cells inhibited the cell surface localization of endogenous E-cadherin, leading to morphological changes, the inhibition of junctional assembly and cell dissociation. These changes were associated with increased cell migration, but were not accompanied by the down-regulation of epithelial markers and up-regulation of mesenchymal markers. Thus, these changes cannot be classified as EMT. The cadherin cytoplasmic domain interacted with ?-catenin or plakoglobin, reducing the levels of ?-catenin or plakoglobin associated with E-cadherin, and raising the possibility that ?-catenin and plakoglobin sequestration by these constructs induced E-cadherin intracellular localization. Accordingly, a cytoplasmic domain construct bearing mutations that weakened the interactions with ?-catenin or plakoglobin did not impair junction formation and adhesion, indicating that the interaction with ?-catenin or plakoglobin was essential to the potential of the constructs. E-cadherin-?-catenin chimeras that did not require ?-catenin or plakoglobin for their cell surface transport restored cell-cell adhesion and junction formation.

SUBMITTER: Ozawa M 

PROVIDER: S-EPMC4133371 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature