Stem vs non-stem cell origin of colorectal cancer

Colorectal cancer (CRC) is one of the most common cancers in the western world and is characterised by deregulation of the Wnt signalling pathway. Mutation of the adenomatous polyposis coli (APC) tumour suppressor gene, which encodes a protein that negatively regulates this pathway, occurs in almost 80% of CRC cases. The progression of this cancer from an early adenoma to carcinoma is accompanied by a well-characterised set of mutations including KRAS, SMAD4 and TP53. Using elegant genetic models the current paradigm is that the intestinal stem cell is the origin of CRC. However, human histology and recent studies, showing marked plasticity within the intestinal epithelium, may point to other cells of origin. Here we will review these latest studies and place these in context to provide an up-to-date view of the cell of origin of CRC.