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, ∆Np63. DeltaNp63 alpha (∆Np63α) is the predominant splice variant of the isoform, ∆Np63 and is expressed in the basal layer of stratified epithelia. ∆Np63α that is normally essential for the epithelial lineage maintenance may be dysregulated in squamous cell carcinomas (SCCs). The pro-tumorigenic or antitumorigenic role of ∆Np63 is a highly contentious arena. ∆Np63α 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-β, Wnt and Notch, as well as epigenetic alterations involving microRNAs, and long noncoding RNAs are regulated by ∆Np63α. This review has attempted to provide an in-depth insight into the role of ∆Np63α in the development of SCCs during different stages of tumor formation and how it may be targeted for therapeutic implications.