Abstract
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 found that while a compartment entirely made by Rab5 mutant cells can grow indefinitely, clones of Rab5 cells surrounded by normal cells are eliminated by cell competition. However, when a group of about 400 cells are simultaneously made mutant for Rab5, they form an overgrowing tumour: mutant cells in the periphery are eliminated, but those inside survive and continue proliferating because they are beyond the range of cell competition. These results identify group protection as a mechanism to evade the tumour-suppressing function of cell competition in Drosophila. Furthermore, we find that the growth of the tumour depends to a large extent on the presence of apoptosis inside the tumour: cells doubly mutant for Rab5 and the proapoptotic gene dronc do not form overgrowing tumours. These results suggest that the apoptosis caused by cell competition acts as a tumour-stimulating factor, bringing about high levels of Jun N-terminal kinase and subsequently Wg/Dpp signalling and high proliferation levels in the growing tumour. We conclude that under these circumstances cell competition facilitates the progression of the tumour, thus reversing its normal antitumour role.
