Notch signaling in melanoma: interacting pathways and stromal influences that enhance Notch targeting

The Notch signaling pathway is an evolutionarily conserved, intercellular signaling cascade. Notch was first described in the early 1900s when a mutant Drosophila showed notches on the wing margins. Studies of the role of Notch signaling have ever since flourished, and the pleiotropic nature of the Notch gene is now evident. Indeed, the Notch signaling pathway plays key roles in cell fate decisions, tissue patterning, and morphogenesis during development. However, deregulation of this pathway can contribute to cell transformation and tumorigenesis. Several reports have now highlighted the role of Notch signaling in a variety of malignancies where Notch can either be an oncogene or a tumor suppressor depending on the cell context. Here, we summarize the major components of Notch signaling with an aim to emphasize the contribution of deregulated Notch signaling in melanomagenesis.