dMyc oncoprotein levels control lethal giant larvae neoplastic growth in Drosophila epithelia

Neoplastic growth requires the cooperation of several oncogenic mutations leading to major rearrangements in cellular behaviour. Premalignant cells are often removed from normal tissues, but the mechanisms orchestrating such a safeguard process remain in part elusive. In Drosophila, cells mutant for the neoplastic tumour suppressors lethal giant larvae (lgl), scribble (scrib) and discs large (dlg) undergo non-autonomous apoptosis when embedded in a wt background. scrib and dlg mutant clones are eliminated from the imaginal tissues through an Eiger-induced endosomal activation of the JNK pathway, a phenomenon named “intrinsic tumour suppression”. We found that, for lgl mutant clones, this latter does not represent the only mechanism of exclusion. In the wing pouch region of the imaginal wing disc, where cell competition acts in eliminating cells with impaired growth, intrinsic tumour suppression inhibition is not able to rescue lgl growth. lgl mutant cells express very low levels of dMyc protein and when juxtapposed to high dMyc-expressing neighbours, as it is in the wing pouch, they are strongly outcompeted, implicating a role for dMyc-induced cell competition in restraining lgl clonal expansion in this territory. In addition, we show how in different backgrounds and tissues lgl clonal behaviour is always correlated to dMyc protein abundance: an increase is invariantly observed when clones are able to overgrow whereas lower levels are associated with poor viability. Our results provide first evidence that, in addition to intrinsic tumour suppression, cell competition is involved in protecting tissues from tumourous growth and identify a specific function for dMyc oncoprotein in cooperating with lethal giant larvae tumour suppressor to promote malignant overgrowth.