Cooperates with Oncogenic in Tumourigenesis via the JNK and PI3K Pathways in epithelial Tissue.

The oncogene (Rat Sarcoma oncogene, a small GTPase) is a key driver of human cancer, however alone it is insufficient to produce malignancy, due to the induction of cell cycle arrest or senescence. In a genetic screen for genes that cooperate with oncogenic (bearing the mutation, or ), we identified the (Sarcoma virus oncogene) family non-receptor tyrosine protein kinase genes, and , as promoting increased hyperplasia in a whole epithelial tissue context in the eye. Moreover, overexpression of cooperated with in epithelial cell clones to drive neoplastic tumourigenesis. We found that overexpression alone activated the Jun N-terminal Kinase (JNK) signalling pathway to promote actin cytoskeletal and cell polarity defects and drive apoptosis, whereas, in cooperation with , JNK led to a loss of differentiation and an invasive phenotype. cooperative tumourigenesis was dependent on JNK as well as Phosphoinositide 3-Kinase (PI3K) signalling, suggesting that targeting these pathways might provide novel therapeutic opportunities in cancers dependent on Src and Ras signalling.