Oncogenic programmes and Notch activity: An ‘organized crime’?

• There is growing evidence that inappropriate Notch signalling can contribute to many aspects of cancer.
• The reiterative use of Notch poses a challenge to manipulate and define specific roles of Notch in cancer cells.
• The genetic toolkits available in Drosophila provides opportunities to discover Notch's cooperating partners in cancer.
• An emerging view is that Notch triggers tumorigenesis by cooperating with other factors, as partners in ‘organized crime’.

The inappropriate Notch signalling can influence virtually all aspect of cancer, including tumour–cell growth, survival, apoptosis, angiogenesis, invasion and metastasis, although it does not do this alone. Hence, elucidating the partners of Notch that are active in cancer is now the focus of much intense research activity. The genetic toolkits available, coupled to the small size and short life of the fruit fly Drosophila melanogaster, makes this an inexpensive and effective animal model, suited to large-scale cancer gene discovery studies. The fly eye is not only a non-vital organ but its stereotyped size and disposition also means it is easy to screen for mutations that cause tumours and metastases and provides ample opportunities to test cancer theories and to unravel unanticipated nexus between Notch and other cancer genes, or to discover unforeseen Notch's partners in cancer. These studies suggest that Notch's oncogenic capacity is brought about not simply by increasing signal strength but through partnerships, whereby oncogenes gain more by cooperating than acting individually, as in a ring ‘organized crime’.