Figure 4.

Blocking autophagy enhances polarity-impaired Ras^V12-driven epithelial tumours. (a) Eye-antennal imaginal discs of ey-FLP-out Act»Ras^V12 dlg^RNAi lacZ (left) or ey-FLP-out Act»Ras^V12 dlg^RNAi Atg8a^RNAi (right) are shown attached to the brain and ventral nerve chord. (b) Autophagy inhibition at the induction (Atg13^RNAi), elongation (Atg8a^RNAi) or fusion to lysosome (Syx17^RNAi) step of the pathway enhanced developmental delay in an ey-FLP-out Act»Ras^V12 dlg^RNAi cooperative model of tumourigenesis. Inhibition of autophagy at the elongation step, using Atg8a^RNAi, accentuated developmental delay, with nearly 40% of animals dying as giant larvae, and only 8% reaching a later pupal stage. Inhibiting autophagy at the autophagosome–lysosome fusion step, using Syx17^RNAi, also delayed development of ey-FLP-out Act»GAL4 Ras^V12 dlg^RNAi larvae, although not as strongly as Atg8a^RNAi, with ~10% dying as giant larvae, and only 11% making it to the later pupal stage. Blocking the initiation step, using Atg13^RNAi, markedly enhanced developmental delay, with only 1% of animals reaching the late pupae stage, and 16% dying as giant larvae. However, inhibiting the pathway at the same step, using Atg1^RNAi, did not have any substantial effect on ey-FLP-out Act»GAL4 Ras^V12 dlg^RNAi development. Error bars=95% confidence intervals.