MYC-Mediated Cell Competition as an Evolutionary Trait of Cancer

MYC-Mediated Cell Competition (MMCC) is a phenomenon of fitness comparison occurring between adjacent cells showing different levels of MYC activity.. It describes a mechanism, conserved from Drosophila to mammalian development, through which cells characterised by high expression of MYC induce apoptotic death of neighbouring low MYC-expressing cells and acquire an advantage in space occupancy. Though it is widely speculated that this phenomenon is relevant to cancer, its characterisation during tumour progression is still missing. Here we show the presence of markers of MMCC in human carcinomas and demonstrate through experiments in human cancer cell lines that MYC modulation is per se sufficient to induce competitive behaviours in both genetically distant and identical cells. Noteworthy, MYC inhibition in the fittest cell line is sufficient to reverse its competitive status. Moreover, data obtained in a Drosophila,cancer model indicate that MMCC is normally at work during tumour growth and that induction of high or low-MYC expressing cells in the growing masses deeply alters the final tumour size, supporting a role for MMCC in cancer evolution.