The malignant growth of lgl- RasV12 tumours depends on Myc function

Simultaneous loss of function of the tumour suppressor gene lethal giant larvae (lgl) and constitutive activation of Ras signalling (RasV12) represent a powerful model of oncogenic cooperation. In the wing disc we have shown that lgl mutant clones are eliminated by cell competition, while lgl-/- RasV12 cells are able to grow and form tumourous masses in which Yorkie, the transcriptional co-activator downstream of the Hippo pathway, is activated. As previously shown, lgl mutant cells require Myc expression to display malignant behaviour and, since Myc is a Yki transcriptional target and Myc protein is stabilised by the MAPK downstream of Ras signalling, we have investigated Myc contribution to lgl-/- RasV12 -induced tumourous traits. We found that Myc activity is necessary for the growth of lgl-/- RasV12 cells and it is sufficient to drive proliferation and invasive behaviour even in the absence of endogenous Ras signalling. Furthermore, our data suggest that both transcriptional and post-transcriptional regulation of Myc are necessary to induce malignant growth in the wing pouch region. Preliminary data will also be presented about a role of hypoxia in promoting changes in FGF signalling and consequent interactions between lgl-/- RasV12 tumours and the tracheal network.