The canonical Wnt pathway. a Wnt is naturally inhibited by inhibitors such as SFRP and WIF. Without a Wnt signal, the β-catenin is captured by APC and Axin, then CK1 and GSK3 phosphorilate β-catenin, leading to proteasomal degradation. Without β-catenin binding, the TCF/LEF family proteins bind with Groucho family proteins, and function as a transcription inhibitor. b When Wnt signaling activated, Wnt binds to specific Frizzled-LRP complexes on the cell surface and initiate the canonical Wnt pathway. The activated receptor complex phosphorylates Dvl. Then Dvl inhibits CK1 and GSK-3, resulting in the accumulation of non-phosphorylated β-catenin in cytoplasm, which cannot be ubiquitinylated for degradation. β-catenin then translocates into the nucleus, and binds with TCF/LEF, causes transcriptional activation of target genes. β-cat β-catenin, LRP low-density lipoprotein receptor-related protein, CK1 casein kinase 1α, GSK-3 glycogen synthase kinase-3β, Dvl disheveled, APC adenomatous polyposis coli, SFRP secreted Frizzledrelated protein, WIF Wnt inhibitory factor, TCF T cell factor, LEF lymphoid enhancer-binding factor.