A study on epithelial-mesenchymal transition mediated by deltaNp63 in invasion and metastasis of oral squamous cell carcinoma

在这项研究中，我们研究了DeltaNp63在口腔鳞状细胞癌(OSCC)进展过程中EMT中的作用。口腔鳞癌组织中可检测到deltaNp63和上皮性标志物的表达，而高转移潜能的SQUU-B细胞中未检测到该基因的表达。间充质标志物在SQUU-B细胞中呈强阳性表达。HSC-2细胞内源性deltaNp63基因敲除后，细胞形态发生纺锤形改变，上皮性标志物表达减少，间质标志物表达增加，迁移增加。相反，过表达deltaNp63的SQUU-B细胞显示其形态发生改变，从间质细胞样细胞转变为上皮细胞。免疫组织化学染色显示，口腔鳞癌组织中DeltaNp63表达强度降低与口腔鳞癌的转移和预后不良呈正相关。这些结果表明，癌细胞中deltaNp63的下调诱导了与口腔鳞癌肿瘤进展相关的间充质表型。

In this study, we investigated the role of deltaNp63 in EMT during progression of oral squamous cell carcinoma (OSCC). The expressions of deltaNp63 and epithelial markers was detected in the OSCC cells, but not in SQUU-B cells (high metastatic potential). Mesenchymal markers were strongly expressed in the SQUU-B cells. Knockdown of endogenous deltaNp63 in HSC-2 cells induced morphological changes to the spindle shape, decreased the expression of epithelial markers, increased the expression of mesenchymal markers, increased migration. By contrast, SQUU-B cells overexpressing deltaNp63 showed changed their morphology from stromal cell-like to epithelial cells. Immunohistochemical staining revealed decreased intensity of deltaNp63 was positively associated with metastases and poor prognosis in the OSCC patients. These results indicated that deltaNp63 downregulation in cancer cells induces a mesenchymal phenotype that is related to tumor progression of OSCC.