Both ERK and Wnt / β - catenin pathways are involved in Wnt 3 a - induced proliferation

Wnt activates the cytoplasmic Disheveled (Dsh) protein leading to inhibition of glycogen synthase kinase 3β (GSK3β) (Lee et al., 1999). Inhibition of GSK3β protects β-catenin against degradation by protein complexes, consisting of GSK3β, axin and adenomatous polyposis coli (APC) In the resting state, very little β-catenin is present in either the cytoplasm or the nucleus because of rapid degradation by the proteasome promoted by the protein complex (Ikeda et al., 1998; Sakanaka et al., 1998). After cytoplasmic accumulation as a result of Wnt signaling, β-catenin is translocated into the nucleus where it cooperates with Tcf/Lef transcription factors for activation of target genes, such as c-Myc and cyclin D1 (He et al., 1998; Tetsu and McCormick, 1999). Regulation of cell proliferation by Wnt signaling relies on activation of c-Myc and cyclin D1, followed by stimulated progression of the cell cycle (Lustig and Behrens, 2003). Aberrant regulation of the Wnt/β-catenin signaling pathway, including upregulation of β-catenin, is one of the major causes of colorectal and other cancers (Giles et al.