Wnt/β-catenin signalling and β-catenin role in adhesion in glioma cells. A) In the absence of Wnt ligands or in the presence of Wnt antagonists Dkk and sFRP that bind to the respective Wnt receptors Fz and LRP5/6, β-catenin is in a complex together with Axin, APC, and Gsk-3β. Here, β-catenin is phosphorylated by Gsk-3β in key Ser and Thr residues and is thus targeted for proteasomal degradation. Frat prevents the phosphorylation of β-catenin. Transcription by Lef/Tcf is off due to the binding of repressors. In the absence of growth factor signaling, a pool of β-catenin is engaged in the cadherin/β-catenin/α-catenin complex that is linked to the cytoskeleton. B) Following Wnt binding, the Fz-LRP5/6 complex is formed upon Dvl phosphorylation that recruits Gsk-3β, Axin, and APC to the membrane. This results in free β-catenin that accumulates in the cytosol and translocates to the nucleus, where it binds to Tcf and recruits transcriptional activators (including Pygo). Lef/Tcf transcriptional activation results in the regulation of Wnt target genes. The box shows Wnt target genes implicated in proliferation and invasion of glioma cells or conferring ES cell signature to GICs that might be related to aggressive growth and recurrence [37–39] EGF signalling through EGFR, ERK1/2, and CK2 results in the phosphorylation of α-catenin and promotes β-catenin transactivation [40]. Whether the Wnt-induced and growth factor-induced β-catenin nuclear pools collaborate in glioma cells remains to be studied. Text in red indicates Wnt pathway components that are overexpressed and green indicates Wnt antagonists repressed in high-grade astrocytomas and GBM. Wnt factors and Fz that have been reported to be upregulated in high-grade astrocytomas and GBM are shown (see references in the text).