From Drosophila to humans: Myc-driven cell competition in cancer

Cell competition was first discovered as a homeostatic mechanism resulting from bi-directional interactions between genetically different cells within a growing tissue. In Drosophila epithelia, neighbouring cell showing different proliferation rates compete for ground occupancy, with the lower-proliferating population undergoing apoptotic death and the higher-proliferating population overgrowing to compensate for cell loss. Recent studies have shown that cell competition is also involved in the selection of the fittest cells during mammalian development. One of the most important factors associated with cell competition is the oncoprotein MYC: cells with high MYC levels win the competition and cells with low MYC levels are eliminated by apoptosis. As MYC over-regulation is a common trait of human cancers, we analysed a variety of human tumour samples in search of an essential signature of cell competition. Strikingly, we repeatably found an impairment in apical-basal cell polarity, MYC overexpression and massive apoptotic death of stromal cells at the outer boundary of the malignant mass. In addition, cell death was also observed in small groups of cancer cells expressing low levels of MYC close to high-MYC expressing tumour cells. To investigate this phenomenon, we have developed a cell culture-based assay using human cancer cell lines showing different levels of MYC. Following co-culture, high MYC-expressing cells survived and overgrew, whereas cells with lower MYC levels showed an impaired growth. These preliminary findings suggest that MYC-mediated cell competition may shape cancer evolution by favouring high MYC-expressing clones.