M.D. Lynch

It has long been suspected that cellular senescence is an anti-cancer mechanism however it has been difficult to understand the advantage for the organism of retaining mutant cells in a post-mitotic state rather than simply deleting them by apoptosis. It is proposed that in certain circumstances apoptosis promotes neoplasia by causing neighboring cells to divide and that the role of cellular senescence is to prevent this. The proposed mechanism may be particularly important in stem cell compartments: Many if not all mammalian stem cells are organized into proliferating units containing a defined number of stem cells for example the colonic crypt contains 4-6 stem cells. Following loss of a stem cell another stem cell within the same niche divides symmetrically to restore the original number. The most important human malignancies arise from tissues maintained by stem cells and there is increasing evidence that stem cells are the targets for at least the initial genetic changes that occur during carcinogenesis. If a subset of stem cells within a niche arises containing an oncogenic mutation then tumour suppressor mechanisms will promote apoptosis of these cells and the niche will then restore the original number of stem cells by replication of both normal and mutated stem cells. Thus paradoxically apoptosis increases turnover of mutant cells with associated risk of further genetic changes. However if instead mutant cells become senescent then the stem cell niche will be progressively filled by senescent cells until either the mutant cells are eliminated or the niche is completely occupied by post-mitotic cells thereby preventing further evolution of the neoplastic clone.

Keywords (Optional): 
replicative senescence
stem cells