Notch signaling in oral squamous neoplasia

Notch signaling is involved in cell-cell communication. It is an evolutionarily ancient mechanism and plays a fundamental role in development. The typical function of Notch signaling is the regulation of cell fate segregation at asymmetric division; however, a role in tumorigenesis has also been suggested. Inactivating mutations of NOTCH1 are present in about 10 % of cases of squamous cell carcinoma of the skin, oral cavity, esophagus, and lung, rendering it one of the most frequently mutated genes in squamous cell carcinoma. Mouse knockout studies have demonstrated that Notch1 is imperative for early development but is dispensable for formation of the squamous epithelium. However, loss of Notch signaling predisposes the epidermis to hyperplasia and increases tumor incidence. This tumor-inducing effect resulting from the loss of Notch signaling is associated with non-cell-autonomous effects that are elicited by subtle alteration of epithelial cell features, generating a wound-like microenvironment in the underlying stroma. We found that Notch1 was expressed specifically in the basal cells of the oral squamous epithelium. In cancer and oral epithelial dysplasia, it was significantly downregulated, suggesting that reduced Notch activity plays a distinct role in oral neoplasia.