APC and colorectal carcinoma: In contrast, without Wnt stimulation, glycogen synthase kinase (GSK)-3 (in a complex with APC) constitutively phosphorylates β-catenin, resulting in its proteasome-dependent degradation.[21] Although genetic and epigenetic changes have been documented in several targets throughout the pathway, mutation in either APC or β-catenin appears to be a crucial element in CRC carcinogenesis.[22] The LEF1 gene itself is not normally expressed in the adult intestinal epithelium, but only observed in the embryos while development is in progress.