Cell competition as a mechanism that can promote tumour growth through JNK activation. Luna L. Ballesteros-Arias, Verónica Saavedra, Ginés Morata. Centro de Biología Molecular Severo Ochoa, Madrid, Spain.

   Drosophila endocytosis-defective cells develop tumour overgrowths in the imaginal discs. We have analysed the tumorigenic potential of cells mutant for rab5, a gene involved in endocytosis. We find that while rab5 deficient clones are subject to cell competition, a compartment entirely made by rab5 cells grows indefinitely. However, when a group of about 400 cells are simultaneously made mutant for rab5, they form an overgrowing tumour: cells in the periphery are eliminated, but those inside survive because they are beyond the range of cell competition. These results identify group protection as a mechanism to evade cell competition in Drosophila tumorigenesis. Furthermore, we find that the tumour growth depends to a large extent on the presence of apoptosis, as tested on a dronc mutant background. These results suggest that the apoptosis caused by cell competition in the periphery may act as a tumour-promoting factor, bringing about high levels of Wg signalling and inducing dMyc activity in the neighbourhood of apoptotic cells. If, in this context the activity of the JNK pathway, and hence Wg signalling, are suppressed, the apoptotic levels and the associated cell proliferation are much reduced. Moreover, tissue architecture is restored, while no signs of tumour growth are observed. We conclude that under these circumstances cell competition facilitates tumour growth through JNK activation, thus reversing its normal anti-tumour role.