Smad7 stabilizes beta-catenin binding to E-cadherin complex and promotes cell-cell adhesion.

Beta-catenin functions both as an adherens junction adhesion protein and as an essential mediator of the canonical Wnt signaling pathway. Wnts stabilize beta-catenin and promote its accumulation in the nucleus, where it regulates transcription of the target genes. Here we show that Smad7 promotes cell-cell adhesion by stabilizing beta-catenin and consequently increases the beta-catenin-E-cadherin complex level at the plasma membrane. A Smad7-Axin interaction disassociates GSK-3beta and beta-catenin from Axin, as well as inhibits the recruitment of Smurf2, an E3 ligase, to beta-catenin, thus protecting beta-catenin from phosphorylation and degradation. Smad7 increases the stabilized beta-catenin to form a complex with E-cadherin and stabilizes the E-cadherin-beta-catenin complex. Thereby, rather than being translocated to the nucleus for regulating the target gene transcription, Smad7-stabilized-beta-catenin is shunted to the E-cadherin complex to modulate cell-cell adhesion.