β-Catenin functions both as a regulator of cadherin-mediated cell-cell adhesion and a mediator of Wnt signaling. Recently, caspase-3-dependent cleavage of β-catenin was demonstrated to occur during apoptosis. Here, we show that β-catenin is proteolytically cleaved in G401 Wilms' tumor cells that were detached from the culture dish. β-Catenin cleavage products of the same electrophoretic mobility were detected in G401 cells after induction of apoptosis with staurosporine and cell cycle arrest by aphidicolin. The detached cells show no sign of anoikis and ≈90% of the floating cells were able to reattach to new dishes. Furthermore, β-catenin was not cleaved in cells cultured on dishes coated with poly(2-hydroxyethylmethacrylate), which inhibits cellular attachment on the dishes, with ≈90% of cells viable under these conditions. All β-catenin cleavage products lost N-terminal and C-terminal regions and were unable to associate with α-catenin, which is responsible for actin filament binding and organization. However, they were still able to associate with E-cadherin. Aggregation assays revealed that the floating cells had weak aggregation compared with the attached cells. These results suggest that the cleavage of β-catenin during cell detachment functions at least in part to remove the α-catenin-binding domain, thereby reducing cell adhesion activity.

Related Articles