Snail-induced down-regulation of ΔNp63α acquires invasive phenotype of human squamous cell carcinoma

p63 is a member of the p53 family and regulates crucial events in the formation of epithelial structures, but the role of p63 in tumor is unclear. We found that Snail-induced epithelialto-mesenchymal transition (EMT) is accompanied by downregulation of p63 in human squamous cell carcinomas (SCC). Delta Np63 alpha is the predominantly expressed p63 isoform in SCC cells. Delta Np63 promoter activity required a CAAT/enhancer binding protein (C/EBP) binding element and was reduced remarkably by Snail. Down-regulation of Delta Np63 alpha and reduction of C/EBP alpha were observed in EMT phenotype cells, which exhibited invasive activity in vitro. p63 knockdown in cells enhanced invasive activity in the presence of E-cadherin. Conversely, forced expression of Delta Np63 alpha y14 blocked invasive activity of cells with the EMT phenotype. These findings indicate that Snail down-regulates Delta Np63 alpha, leading to acquisition of the invasive phenotype by SCC. The invasive activity caused by down-regulation of Delta Np63 alpha, does not require down-regulation of E-cadherin.