FIGURE 1.

Non-activated canonical Wnt signaling pathway and the drug targeted components. (1) In the absence of Wnt signaling transduction, Axin, GSK3, CK1, and APC form a multiprotein destructive complex to promote β-catenin phosphorylation. In the negative feedback regulation, PP1 promotes dephosphorylation of Axin and subsequent disassembly of multiprotein destructive complex, whereas PP2A binds to Axin and/or APC and directs β-catenin dephosphorylation. (2) β-Trcp binds to the phosphorylated β-catenin for β-catenin ubiquitination. (3) Proteasomal degradation of the ubiquinated and phosphorylated β-catenin results in cytoplasmic β-catenin destruction. (A) WIF1 directly binds to Wnt for inhibition of Wnt binding to Fzd. (B) XAV939 inhibits activity of TNKS and thus promotes Axin upregulation. (C) Indomethacin promotes β-catenin degradation by phosphorylating β-catenin. (D) Aspirin acts as an inhibitor for negative feedback regulation modulated by PP2A and eventually directs β-catenin phosphorylation.