Notch signalling in cancer

Notch signalling is crucial for the normal development of both lower organisms and mammals. It plays a critical role in the determination of cell fates and maintenance of progenitors in many developmental systems by mediating homotypic and heterotypic interaction. Notch function is important for the normal development of many tissues, including muscle, peripheral nervous system, haematopoietic system, etc. Subsequently, it has become clear that Notch signalling is involved in stem cell self-renewal and is able to regulate the main functions of cell life at different levels of development: cell proliferation, differentiation and apoptosis. By virtue of its wide involvement in the regulation of cell physiology it is not surprising that a deregulation in Notch pathway leads to tumour development. Indeed mutations in human Notch1 are involved in more than 50% T acute lymphoblastic leukaemia and to a lesser extent in the pathogenesis of a series of other human neoplasms. Interestingly, the ability of Notch signalling to regulate cell functions, positively or negatively in different cellular context, reflects the behaviour of Notch as both oncogene and tumour suppressor gene depending upon the tumour origin.