Wnt signalling pathway in the serrated neoplastic pathway of the colorectum: possible roles and epigenetic regulatory mechanisms

The role of Wnt signalling in the serrated neoplastic pathway of colorectal tumourigenesis appears to be heterogeneous. Wnt pathway abnormalities contribute to the progression of at least a subset of traditional serrated adenomas of the colorectum, but may play a less active role in its pathogenesis compared with that in conventional adenoma-carcinoma. However, immunohistochemical studies of beta-catenin in sessile serrated adenomas have shown wide variability, producing conflicting results on Wnt signalling activation in sessile serrated adenomas. DNA methylation, involving APC, SFRPs and mutated in colorectal cancer (MCC), may bridge the mutational gap of APC or beta-catenin for activating Wnt signalling in serrated adenomas of the colorectum.