Abstract
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). DeltaNp63alpha is the predominantly expressed p63 isoform in SCC cells. DeltaNp63 promoter activity required a CAAT/enhancer binding protein (C/EBP) binding element and was reduced remarkably by Snail. Down-regulation of DeltaNp63alpha and reduction of C/EBPalpha 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 DeltaNp63alpha blocked invasive activity of cells with the EMT phenotype. These findings indicate that Snail down-regulates DeltaNp63alpha, leading to acquisition of the invasive phenotype by SCC. The invasive activity caused by down-regulation of DeltaNp63alpha does not require down-regulation of E-cadherin.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
CCAAT-Enhancer-Binding Proteins / metabolism
-
Carcinoma, Squamous Cell / genetics
-
Carcinoma, Squamous Cell / metabolism*
-
Carcinoma, Squamous Cell / pathology*
-
Cell Line, Tumor
-
DNA-Binding Proteins / biosynthesis
-
DNA-Binding Proteins / deficiency*
-
DNA-Binding Proteins / genetics
-
Down-Regulation
-
Epithelial Cells / pathology
-
Female
-
Gene Expression Regulation, Neoplastic
-
Humans
-
Mesoderm / pathology
-
Mouth Neoplasms / genetics
-
Mouth Neoplasms / metabolism
-
Mouth Neoplasms / pathology
-
Neoplasm Invasiveness
-
Promoter Regions, Genetic
-
Snail Family Transcription Factors
-
Trans-Activators / biosynthesis
-
Trans-Activators / deficiency*
-
Trans-Activators / genetics
-
Transcription Factors / genetics
-
Transcription Factors / metabolism*
-
Tumor Suppressor Proteins / biosynthesis
-
Tumor Suppressor Proteins / deficiency*
-
Tumor Suppressor Proteins / genetics
-
Vulvar Neoplasms / genetics
-
Vulvar Neoplasms / metabolism
-
Vulvar Neoplasms / pathology
Substances
-
CCAAT-Enhancer-Binding Proteins
-
CEBPA protein, human
-
DNA-Binding Proteins
-
Snail Family Transcription Factors
-
TP63 protein, human
-
Trans-Activators
-
Transcription Factors
-
Tumor Suppressor Proteins