The Notch pathway in cancer: Differentiation gone awry

The Notch signalling cascade influences several key aspects of normal development by regulating differentiation, proliferation and apoptosis. Its association to human cancer is firmly established in T-cell leukaemia where point mutations or chromosomal translocations lead to constitutive signalling. Accumulating data indicate that deregulated Notch activity is involved also in the genesis of other human cancers, such as pancreatic cancer, medulloblastoma and mucoepidermoid carcinoma. In these tumours, the oncogenic effect of Notch signalling reflects an aberrant recapitulation of the highly tissue-specific function of the cascade during normal development and in tissue homeostasis.