Dysregulation of delta Np63 alpha in squamous cell carcinoma and its therapeutic targeting

The gene p63 has two isoforms -a full length transactivated isoform (TA) p63 and an amino-terminally truncated isoform, triangle Np63. DeltaNp63 alpha (triangle Np63 alpha) is the predominant splice variant of the isoform, triangle Np63 and is expressed in the basal layer of stratified epithelia. triangle Np63 alpha that is normally essential for the epithelial lineage maintenance may be dysregulated in squamous cell carcinomas (SCCs). The pro-tumorigenic or antitumorigenic role of triangle Np63 is a highly contentious arena. triangle Np63 alpha may act as a double-edged sword. It may either promote tumor progression, epithelial-mesenchymal transition, migration, chemoresistance, and immune-inflammatory responses, or inhibit the aforementioned phenomena depending upon cell type and tumor microenvironment. Several signaling pathways, transforming growth factor-beta, Wnt and Notch, as well as epigenetic alterations involving microRNAs, and long noncoding RNAs are regulated by triangle Np63 alpha. This review has attempted to provide an in-depth insight into the role of triangle Np63 alpha in the development of SCCs during different stages of tumor formation and how it may be targeted for therapeutic implications.