⑶Wnt signaling pathway
Wnt growth factors play prominent pleiotropic roles in cell–cell communication, including the control of cell fate, proliferation, and stem cell maintenance [60]. Studies have found that YAP/TAZ is a downstream effector of the Wnt signaling pathway[4,61]. YAP/TAZ is a component of the β-catenin destruction complex. In the absence of Wnt ligands, YAP/TAZ binds to Axin and recruits β-TrCP to degrade β-catenin. In the presence of Wnt ligands, YAP/TAZ is released from the complex, and β-catenin enters the nucleus, thus activating the pathway [60]. Wnt5a/b and Wnt3a induce YAP/TAZ activation to promote YAP/TAZ activation and TEAD-mediated transcription [61]. The study also found that the Wnt3a/EGF signaling pathway induces the nuclear translocation of YAP/TAZ by expressing Arl4c in the predilated duct, and YAP/TAZ enhances the expression of Arl4c induced by Wnt3a/EGF[62]. The Wnt signaling pathway can transcriptionally induce the expression of YAP/TAZ and TEAD1/2/4. YAP/TAZ is normally only localized to the nucleus in crypt basal stem cells, but during intestinal regeneration or organoid growth, YAP/TAZ is present in the nucleus in most intestinal epithelial cells in a Src family kinase-dependent manner. Thus, Wnt and SrcYAP/TAZ signaling together promote intestinal regeneration [63]. However, YAP/TAZ and TEAD jointly block the induction of mesoderm genes by SMAD2/3, indicating that the Wnt/β-catenin and SMAD2/3 pathways jointly inhibit YAP/TAZ and promote the EMT process[64].