Stem cell competition: how speeding mutants beat the rest

Abstract

How mutations lead to tumor formation is a central question in cancer research. Although cellular changes that follow the occurrence of common mutations are well characterized, much less is known about their effects on the population level. Now, two recent studies reveal in what way oncogenic aberrations alter stem cell dynamics to provide cells with an evolutionary advantage over their neighbors (Amoyel et al, ; Baker et al, 2014).

Figure 1. Stem cell dynamics and oncogenic transformation

(A) Both fly testis (cyst) stem cells and human ISCs behave in similar fashion. During homeostasis, stem cells continuously compete with their neighbors randomly replacing them or being replaced. (B) Amoyel et al have shown that mutations can confer a competitive advantage by speeding up the mutant stem cell proliferation rate which in turn makes the stem cells more likely to take up vacant niche positions. (C) A potential consequence of this elevated proliferation, once all stem cells are mutant, is the overwhelming of homeostatic control mechanisms leading to higher numbers of stem cells compared to wild type. This would explain the observation by Baker et al for human adenomatous crypts, where the crypts were found to have a larger number of stem cells with an accelerated stem cell replacement rate.