Cell mixing induced by myc is required for competitive tissue invasion and destruction

Live imaging of myc -driven competition in healthy Drosophila tissues shows that cells expressing higher levels of myc actively mix with the neighbouring cells, which increases the probability of eliminating neighbouring cells. Myc-driven cell competition Cells are known to compete with each other: fast-proliferating cells (winners) can cause the demise of slower-proliferating (loser) cells. This process can be triggered by the cancer-associated protein Myc. To investigate interaction between the winners and losers in living organisms, Eduardo Moreno and performed live imaging of myc -driven competition in healthy Drosophila tissues. They find that that cells expressing higher levels of myc actively mix with the neighbouring cells, increasing the probability that they will eliminate the competition. Specifically, cell–cell intercalation is driven by differences in tension at the interface between various cell combinations: winner–winner, winner–loser and loser–loser. At a molecular level, variations in the levels of F-actin at cell junctions due to differential levels of the membrane lipid PIP3 result in tension differences. The outcome is tissue destruction and invasion. Cell–cell intercalation is a well-established phenomenon during development, but these findings suggest that it can also occur in the context of disease. Cell–cell intercalation is used in several developmental processes to shape the normal body plan 1 . There is no clear evidence that intercalation is involved in pathologies. Here we use the proto-oncogene myc to study a process analogous to early phase of tumour expansion: myc -induced cell competition 2 , 3 , 4 , 5 , 6 , 7 . Cell competition is a conserved mechanism 5 , 6 , 8 , 9 driving the elimination of slow-proliferating cells (so-called ‘losers’) by faster-proliferating neighbours (so-called ‘winners’) through apoptosis 10 and is important in preventing developmental malformations and maintain tissue fitness 11 . Here we show, using long-term live imaging of myc -driven competition in the Drosophila pupal notum and in the wing imaginal disc, that the probability of elimination of loser cells correlates with the surface of contact shared with winners. As such, modifying loser–winner interface morphology can modulate the strength of competition. We further show that elimination of loser clones requires winner–loser cell mixing through cell–cell intercalation. Cell mixing is driven by differential growth and the high tension at winne