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. 2007 Oct 1;67(19):9207-13.
doi: 10.1158/0008-5472.CAN-07-0932.

Snail-induced down-regulation of DeltaNp63alpha acquires invasive phenotype of human squamous cell carcinoma

Koichiro Higashikawa  1 , Shingo Yoneda, Kei Tobiume, Masayuki Taki, Hideo Shigeishi, Nobuyuki Kamata
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Snail-induced down-regulation of DeltaNp63alpha acquires invasive phenotype of human squamous cell carcinoma (VSports)

Koichiro Higashikawa et al. Cancer Res. .

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. VSports手机版.

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