Snail-induced downregulation of deltaNp63 acquires invasive phenotype of human squamous cell carcinoma

p63是p53家族的一员，调节上皮结构形成中的关键事件，但p63在肿瘤中的作用尚不清楚。我们发现，蜗牛诱导的上皮间质转化（EMT）伴随着下调p63在人类鳞状细胞癌（SCC）。Δ Np 63 α是SCC细胞中主要表达的p63同种型。deltaNp 63启动子活性需要C/EBP结合元件，并被Snail显著降低。在EMT表型细胞中观察到deltaNp 63 α的下调和C/EBPalpha的减少，其在体外表现出侵袭活性。在E-钙粘蛋白存在下，细胞中p63敲低增强了侵袭活性。相反，deltaNp 63 α的强制表达阻断了具有EMT表型的细胞的侵袭活性。这些发现表明Snail下调deltaNp 63 α，导致SCC获得侵袭性表型。deltaNp 63 alpha下调引起的侵袭活动不需要E-钙粘蛋白下调。

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 downregulation of p63 in human squamous cell carcinomas (SCCs). deltaNp63alpha is the predominantly expressed p63 isoform in SCC cells. deltaNp63 promoter activity required a C/EBP binding element and was reduced remarkably by Snail. Downregulation 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 downregulates deltaNp63alpha, leading to acquisition of the invasive phenotype by SCC. The invasive activity caused by downregulation of deltaNp63alpha does not require downregulation of E-cadherin.