Modelling cooperative tumourigenesis in Drosophila: understanding the link between cell polarity, cell signalling, tissue growth and tumourigenesis

We have identified novel tumour suppressors that cooperate with oncogenic Ras (RasV12) in cancer progression in a genetic screen in collaboration with Professor Josef Penninger (IMBA, Vienna, Austria). These novel tumour suppressors include Tetraspanins, Autophagy, vesicular trafficking, cytoskeletal and metabolic regulators. We seek to determine how knockdown of these tumour suppressors results in tumourigenesis with RasV12.

We are currently focusing on genes involved in Autophagy, which is a catabolic process involved in the break down of proteins and organelles in order to generate energy, and is important in cell survival under stress conditions. We have found that knockdown of autophagy genes cooperates with RasV12 to promote hyperplasia of the Drosophila eye. We have dissected the mechanism by which this occurs and have found that autophagic gene knockdown together with RasV12leads to an upregulation of the JNK signalling pathway, and that this is crucial for the cooperation.

This is in agreement with our previous data showing that JNK signalling cooperates with RasV12 to enhance tissue overgrowth (Brumby et al., 2011). We are also investigating a Tetraspanin, which is a four-pass membrane protein involved in signalling pathway regulation, which acts via a novel mechanism to cooperate with RasV12 in tumourigenesis.