Primers on molecular pathways - Notch

Notch, initially discovered and well characterized in Drosophila due to the notches apparent in the wing blades of mutant strains, and its signaling pathway play a key role in cell-cell communication, which involves gene regulation mechanisms that control multiple cell differentiation processes during embryonic and adult life, including timely cell lineage specification of both the endocrine and exocrine pancreas. This pathway serves as an excellent model signaling cascade for the regulation of the transition from normal ductal epithelium to metaplasia to cancer. In human pancreatic cancer, the change in epithelial differentiation programming is an early hallmark. Several of these changes, including activation of the Notch pathway, which are observed in pathological scenarios, are also seen during normal embryonic development of the pancreas. Notch receptors, ligands as well as downstream targets have been identified to be upregulated in preneoplastic lesions to invasive pancreatic cancers in humans and mice, suggesting that Notch signaling may be an early event leading to accumulation of undifferentiated precursor cells in pancreatic cancers.