The dark side of fly TNF: an ancient developmental proof reading mechanism turned into tumor promoter.

The fruit fly Drosophila is an important model for biological research; however, due to its relatively short lifespan its relevance in cancer research is often questioned. Nevertheless, among many other intriguing Drosophila models, scribble group mutants provided early evidence for the existence of tumor suppressor genes and their importance in mammalian systems is beginning to emerge. In this review, I discuss recent advances in our understanding of the phenotypes of scrib group mutants, in which the activation of JNK signaling plays a crucial role. Several mechanisms can account for the activation of JNK within scrib group mutant cells, including a mechanical stress triggered by the loss of polarity, cell competition, intrinsic tumor suppression by autonomous production of Eiger, and an inflammatory response mediated by Eiger-producing haemocytes. Eiger, the sole Drosophila homolog of tumor necrosis factor, is emerging as a 'danger signal' initiated upon the presence of external pathogens, damaged tissues and the appearance of pre-malignant cells. Remarkably, in the presence of the Ras oncoprotein Eiger can act as a tumor promoter by stimulating invasive migration and delaying the onset of metamorphosis.