The winner takes it all: competition between NIH3T3 cells

Cell competition is a unique type of short-range communication originally identified in Drosophila embryos, whereby cells with relatively higher fitness than their neighbours become ‘winners’ and those with lower fitness are eliminated as ‘losers’. In Drosophila imaginal discs, genes affecting proliferation have been shown to induce cell competition, including Myc and the Hippo co-activator Yorkie, with their overexpression resulting in ‘super-competitor’ cells. However, it is unclear whether cell competition exists in mammalian or non-epithelial cells. Hiroshi Sasaki and co-workers now (p.790) establish an in vitro assay for cell competition using the mouse embryonic fibroblast cell line NIH3T3, in which they modulate the activity of the Tead transcription factor. Tead was chosen because it is regulated by Hippo signalling, which controls proliferation and apoptosis in these cells. Co-culturing of wild-type NIH3T3 cells with those that had modulated Tead activity indeed resulted in cell competition behaviour; cells with high levels of Tead became super-competitors, whereas cells with reduced levels were losers. Interestingly, at low cell density, proliferation required both Tead and Myc activity, whereas, at high cell density, a decrease in either of these factors could be compensated for by an increase in the other, resulting in winner behaviour. These results indicate that cell competition indeed exists in mammalian fibroblast cells and that such an assay could further elucidate the mechanisms underlying this behaviour.