Modelling the effect of subcellular mutations on the migration of cells in the colorectal crypt

摘要

Colorectal cancer (CRC) is one of the most common forms of cancer and a leading cause of cancer death in the western world [ ]. CRC’s initiation has been attributed to a loss of control over the proliferation and migration of colon crypt cells [ , ] with cell proliferation and crypt production processes playing crucial roles in the growth of colorectal adenomas and hyperplastic polyps [ ]. The Wnt signalling pathway has been linked to intestinal crypt formation, cell proliferation [ – ] and the regulation of cell-cell adhesion in crypts [ , ]. With 90% of CRCs having mutations in key components of the Wnt pathway, i.e. adenomatous polyposis coli (APC) or -catenin ( -cat) [ ], it is inevitable that this pathway attracts considerable attention. Oddly, the importance of cell-cell adhesion’s association with -cat has often being overlooked, particularly as E-cadherin (E-cad) has several critical functions, including facilitating the normal homeostasis and morphogenesis of the intestine [ , ], serving as a tumor suppressor gene [ ] and preventing invasiveness in carcinomas cells [ ]. Currently, neither the roles of Wnt signalling and cell-cell adhesion in the colon nor the links between the underlying APC, -catenin and E-cadherin biochemistry and adenoma formation are well understood.