APC and neoplasm: In the canonical pathway to CRC, the primary driving force is mutant APC-mediated activation of Wnt/β-catenin signaling (Morin et al., 1997), and the ‘just-right’ level of Wnt/β-catenin signaling optimal for tumor formation is achieved mainly by the selection for specific APC mutant proteins based on their residual β-catenin-downregulating activity (Albuquerque et al., 2002; Leedham et al., 2013; Christie et al., 2013; Buchert et al., 2010).