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 epithelial-to-mesenchymal transition (EMT) is accompanied by down-regulation of p63 in human squamous cell carcinomas (SCC). ΔNp63α is the predominantly expressed p63 isoform in SCC cells. ΔNp63 promoter activity required a CAAT/enhancer binding protein (C/EBP) binding element and was reduced remarkably by Snail. Down-regulation of ΔNp63α and reduction of C/EBPα 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 ΔNp63α blocked invasive activity of cells with the EMT phenotype. These findings indicate that Snail down-regulates ΔNp63α, leading to acquisition of the invasive phenotype by SCC. The invasive activity caused by down-regulation of ΔNp63α does not require down-regulation of E-cadherin. [Cancer Res 2007;67(19):9207–13]