p63 and p73 - Life and death in squamous cell carcinoma

The p53 family member p63 plays an essential role in the developing epithelium, and overexpression of the Delta Np63 alpha isoform is frequently observed in human squamous cell carcinomas (SCCs). These findings have suggested that Delta Np63 alpha might function as an oncogene within squamous epithelial cells. Nevertheless, the mechanism by which Delta Np63 alpha might promote tumorigenesis remains poorly understood, and data from mouse models implies that the p63 locus might in fact function as a tumor suppressor in these same tissues. A recent study using RNA interference in human SCC-derived cell lines shows that Delta Np63 alpha mediates an essential survival function in human SCC cells by virtue of its ability to suppress the pro-apoptotic function of the related p53 family member p73. These findings support an oncogenic role for Delta Np63 alpha and they demonstrate the existence of critical physical and functional interactions between endogenous p53 family members in human cancer. Specific chemotherapeutic agents and future targeted approaches may be able to exploit this pathway to therapeutic advantage.