Apoptosis and colorectal cancer

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Abstract
Before discussing apoptosis itself it is important to understand the hierarchical organisation of intestinal epithelium as this is central to any appreciation of the pathogenesis of colorectal cancer. Colonic epithelial cells are configured in deep invaginations into the wall of the colon called crypts. These cells arise from stem cells that are located at the base of the crypt and migrate to the luminal surface of the crypt where they are shed.2 Evidence is accumulating that stem cells do not have unique intrinsic properties but rather are epithelial cells that acquire self renewal together with related properties as a result of being located within a specialised niche.3 To date, no markers for stem cells have been identified although significant advances have been made towards this holy grail.4 Stem cells divide asymmetrically, with newly synthesised DNA donated to daughter cells that migrate up the crypt ultimately to be shed while “old” DNA is retained in the stem cell population.5 This renders the stem cell particularly vulnerable to developing mutations that might evolve into a malignant clone. To counteract this possibility, cells at the base of crypts, and therefore presumably stem cells, are highly prone to apoptosis, an altruistic form of cell death that rids the organism of cells harbouring dangerous mutations.6