Figure 1. Schematic representation of the canonical (Wnt/β-catenin) and non-canonical (Wnt/Ca²⁺ and Wnt/PCP) signaling pathways.

Drugs used in the experiments and their action on Wnt signaling pathways are figured in black. Activation and inhibition are symbolized by and , respectively. In the presence of Wnt ligand, Fzd and LRP5/6 form a receptor complex leading to the recruitment of cytosolic proteins Dsh and LRP5/6 phosphorylation. The phosphorylation and partial internalization of LRP5/6 initiate the disruption of the destruction complex (axin, APC, CK-1, and GSK-3β), allowing cytosolic β-catenin accumulation and then translocation into the nucleus, where β-catenin serves as a coactivator of TCF/LEF transcription factors to control gene transcription. Depending on the cellular context, the non-canonical Wnt signaling pathway is stimulated by the binding of Fzd and ROR2/RYK coreceptors. The Wnt/Ca²⁺ pathway induces PKC activation via the intracellular Ca²⁺ increase. The Wnt/PCP pathway activates the small G proteins Rho and the MAPK cascade via the recruitment of the cytosolic proteins Dsh and DAAM1, or, alternatively, triggers activation of JNK leading to the transcription of target genes through AP-1 activation.