WFDC2 contributes to epithelial-mesenchymal transition (EMT) by activating AKT signaling pathway and regulating MMP-2 expression.
WFDC2 contributes to epithelial-mesenchymal transition (EMT) by activating AKT signaling pathway and regulating MMP-2 expression.
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WFDC2 通过激活 AKT 信号通路和调节 MMP-2 表达来促进上皮间质转化 (EMT)。
作者：
陈瑶;黄莉萍;王穗海;李继良;李明;吴英松;刘天才
目的：探讨WFDC 2在卵巢癌转移中的作用。方法：通过敲低或过表达WFDC 2，我们证明了WFDC 2在上皮间质转化（EMT）中的作用。结果：稳定敲除WFDC 2可抑制EMT沿着上调E-cadherin和下调Vimentin。此外，在体外细胞模型和体内裸鼠异种移植物中，WFDC 2敲低降低基质金属蛋白酶-2（MMP-2）表达。临床标本中WFDC 2与MMP-2表达的相关性证实WFDC 2与肿瘤的发生发展密切相关。更重要的是，siMMP-2和P13 K/AKT信号抑制剂可以逆转WFDC 2过表达诱导的EMT表型和细胞侵袭。结论：WFDC 2通过激活AKT信号通路，诱导MMP-2表达，促进卵巢癌转移和EMT的发生。关键词：WFCD 2，卵巢癌，转移，细胞迁移和侵袭，上皮间质转化
Objective: To understand the role of WFDC2 in metastasis of ovarian cancer..Methods: By knockdown or overexpression of WFDC2, we demonstrated the role of WFDC2 in epithelial–mesenchymal transition (EMT)..Results: We demonstrated that stable knockdown of WFDC2 suppressed EMT along with the upregulation of E-cadherin and the downregulation of Vimentin. In addition, WFDC2 knockdown decreases matrix metalloproteinase-2 (MMP-2) expression in in vitro cell model and in in vivo nude mice xenografts. The correlation of WFDC2 and MMP-2 expression in the clinical sample confirmed that WFDC2 was tightly correlated with the development of tumor. More importantly, the EMT phenotype and cell invasion induced by WFDC2 overexpressing can be reversed by the siMMP-2 and P13K/AKT signaling inhibitor..Conclusion: WFDC2 contributed to ovarian cancer metastasis and EMT as a positive regulator by activating AKT signaling pathway and inducing MMP-2 expression..Keywords: WFCD2, ovarian cancer, metastasis, cell migration and invasion, epithelial mesenchymal transition