Tumour growth and tracheogenesis are separable cancer hallmarks in Drosophila

Clonal analysis is common practice in Drosophila. In particular, induction of cell clusters carrying both loss-of-function alleles of neoplastic tumour suppressors and activated forms of oncogenes has successfully been exploited to study cooperative tumourigenesis in different organs. This strategy has allowed to collect a number of morphological and molecular details on the phenotypic traits associated with cancer evolution. We previously identified Myc as a target of the Hippo pathway in Drosophila, and found out that its expression is sufficient to rescue the growth deficit of cells mutant for polarity genes, releasing their malignant potential. We also previously characterised cancer-associated tracheogenesis, a process analogue to mammalian neo-angiogenesis, as an intrinsic trait of Drosophila epithelial tumours. Here we expand on previous work, showing that tumour growth and tracheogenesis are separable traits in Drosophila epithelia. While in situ cancer expansion is mainly supported by Myc, this is not the case for migration and tracheogenesis, which mostly depend on Fos activity. These proteins are strategically found at the crossroads of the Hippo, JNK and Ras/MAPK pathways, which current literature recognises as key players in cancer progression.