Interaction between Smad7 and β-Catenin: Importance for Transforming Growth Factor β-Induced Apoptosis

Members of the transforming growth factor β (TGF-β) and Wnt/wingless superfamilies regulate cell fate during development and tissue maintenance. Here we report that Smad7 interacts with β-catenin and lymphoid enhancer binding factor 1/T-cell-specific factor (LEF1/TCF), transcriptional regulators in Wnt signaling, in a TGF-β-dependent manner. Smad7 was found to be required for TGF-β1-induced accumulation of β-catenin and LEF1 in human prostate cancer (PC-3U) cells as well as in human keratinocytes (HaCaT cells). Moreover, when the endogenous Smad7 was repressed by specific small interfering RNA, TGF-β-induced increase of activated p38, Akt phosphorylated on Ser473, glycogen synthase kinase 3β phosphorylated on Ser9 was prevented, as well as the TGF-β-induced association between β-catenin and LEF1. Notably, the observed physical association of Smad7 and β-catenin was found to be important for TGF-β-induced apoptosis, since suppression of β-catenin expression by small interfering RNA decreased the apoptotic response to TGF-β.