Wnt/β-catenin pathway
Wnt pathway in essence comprises of canonical (β-catenin dependent) and
noncanonical (β-catenin-independent) signaling pathway. Here, we focus
on canonical pathway which is found to be implicated in survival of most
of the CSCs. In canonical Wnt signaling pathway, in the absence of Wnt
ligands (Wnt3a and Wnt1), β-catenin is phosphorylated due to its
interaction with the destruction complex, which consists of the scaffold
protein Axin, APC and GSK3β kinase and casein kinase (CK1α). This
phosphorylation brings about ubiquitination and degradation of
β-catenin. On the other hand, the pathway is activated when Wnt ligands
bind to Frizzled (Fzd) receptors and/or the low-density
lipoprotein-related protein (LRP) co-receptors. As a result, Dishevelled
(Dvl) proteins are recruited and Dvl polymers inactivate the destruction
complex. This results in stabilization and accumulation of β-catenin
which then translocates into the nucleus, binds to lymphoid enhancer
factor (LEF)/T-cell factor (TCF) transcription factors, and facilitates
transcription of various target genes (Zhan et al., 2017) .