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].