Inactivation of the APC tumour suppressor gene represents the rate-limiting event in colorectal cancer. Loss of APC function leads to constitutive activation of the canonical Wnt-β-catenin signalling pathway, thus resulting into a broad spectrum of cellular defects, ranging from stem cell self-renewal and differentiation, apoptosis, migration and proliferation. Recently, Phelps et al [1] presented an alternative model where loss of APC does not primarily result in Wnt signalling activation but rather involves the transcriptional co-repressor CtBP1. According to this alternative scenario, oncogenic KRAS activation represents a conditio sine qua non for nuclear β-catenin translocation and Wnt activation. In a recent issue of the Journal of Pathology, Obrador-Hevia and collaborators [2] reaffirmed the broadly accepted textbook model by showing the presence of nuclear β-catenin in both the presence and, more often, the absence of KRAS mutations. Copyright

β-catenin (CTNNB1), Adenomatous polyposis coli (APC), Colon cancer, KRAS, Wnt signalling,
Journal of Pathology
Department of Pathology

Fodde, R, & Tomlinson, I.P. (2010). Nuclear β-catenin expression and Wnt signalling: In defence of the dogma. Journal of Pathology (Vol. 221, pp. 239–241). doi:10.1002/path.2718