FIGURE 1.

Overview of the Wnt pathway. (A) Canonical pathway. Binding of Wnt to frizzled receptors activates disheveled (DVL), which disrupts the stability of the destruction complex, composed of Axin, APC, GSK3-β, CK1, and β-catenin. Subsequently, phosphorylation and degradation of β-catenin are inhibited, which allows the association of β-catenin with TCF transcription factors. In the absence of Wnt ligands, the complexes promote phosphorylation of β-catenin. Phosphorylated β-catenin becomes multiubiquitinated (Ub) and subsequently degraded in proteasomes (Foulquier et al., 2018). (B) Non-canonical pathway. In the Wnt/Ca²⁺ pathway, Wnt ligands bind to a complex consisting of Fzd, DVL, and G-proteins, leading to the activation of PLC, which cleaves phosphatidylinositol 4,5 biphosphate (PIP2) into diacylglycerol (DAG) and IP3. DAG activates PKC whereas IP3 promotes the release of intracellular Ca²⁺, which in turn activates CamKII and calcineurin (Russell and Monga, 2018). Calcineurin activates NFAT to regulate cell migration and cell proliferation. In the PCP pathway, Wnt ligands bind to a complex consisting of Fzd, Ror2, and DVL, which mediates the activation of RhoA and ROCK, or activation of Rac and JNK signaling, to regulate cell polarity and migration.