Cancer is a cooperative process, involving mutations in multiple genes. Activation of a cancer-driving gene, the Ras small GTPase, via a mutation that locks Ras in the GTP-bound active form (RasV12), occurs in ~30% of human cancers. However, alone it is not sufficient for tumour formation. A loss of function screen previously performed in the vinegar fly, Drosophila melanogaster,identified 947 genes that potentiate RASV12-mediated tumourigenesis and metastasis (Zoranovic et al., in prep). We have narrowed down this list to 234 genes that 1) show increased tumourigenicity with RASV12in vivo, 2) are in the top 100 genes down-regulated in human cancer, and 3) are known to regulate the cytoskeleton, polarity, adhesion or cell motility. Our study will allow the identification of cooperative tumour suppressors in Ras-mediated tumourigenesis and metastasis in vivo in Drosophila. We have successfully confirmed involvement of a few genes from the list in regulating RasV12-mediated proliferation in the Drosophila eye tissue using the UAS/GAL4 system. Amongst them, we have identified the autophagy-related genes Atg1, Atg3, Atg5, Atg6, Atg7, Atg8, Atg12, Atg101 which cooperate with RasV12leading to increased tissue overgrowth in Drosophila eye tissue. We have found that Atg8 and Atg101 cooperate with RasV12 through the Raf pathway. We are currently further analysing the mechanism of cooperation of Atg genes with RasV12 in epithelial tissue growth and tumourigenesis. These genes could serve as prognostic markers in Ras-driven oncogenesis and might reveal effective therapeutic targets to combat this deadly disease.