Small interfering RNA targeting ILK inhibits metastasis in human tongue cancer cells through repression of epithelial-to-mesenchymal transition
Small interfering RNA targeting ILK inhibits metastasis in human tongue cancer cells through repression of epithelial-to-mesenchymal transition
复制标题
靶向 ILK 的小干扰 RNA 通过抑制上皮间质转化来抑制人舌癌细胞的转移
DOI：
10.1016/j.yexcr.2013.05.014
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发表时间：
2013-08-01
影响因子：
3.7
通讯作者：
Chen, Junxia
中科院分区：
文献类型：
--
作者：
Xing, Yu;Qi, Jin;Chen, Junxia
整合素连接的激酶(ILK)是一种多功能的丝氨酸/苏氨酸激酶。越来越多的证据表明，ILK参与细胞-基质相互作用、细胞增殖、侵袭、迁移、血管生成和上皮-间充质转化(EMT)。然而，潜在的机制在很大程度上仍不清楚。EMT一直被认为是转移的先决条件。研究表明，EMT与口腔鳞状细胞癌的转移有关。因此，我们进一步推测ILK可能参与舌癌的EMT。我们发现，在体内和体外，ilk siRNA在低N-钙粘蛋白、Vimentin、Snail、Slug和Twist的情况下抑制EMT，而在E-钙粘素的高表达的情况下抑制EMT。我们发现，ILK基因的敲除抑制了细胞的增殖、迁移和侵袭，并改变了细胞的形态。我们还证明了ilk siRNA抑制了下游信号转导靶Akt和GSK3β的磷酸化，并减少了MMP2和MMP9的表达。此外，临床标本中转移能力高的舌癌组织中ILK、Vimentin、Snail、Slug和Twist的表达较高，而E-cadherin的表达较低。最后，ILK siRNA在体内抑制了肿瘤的发生和转移。我们的发现表明，ILK可能成为舌癌的一个新的诊断和治疗靶点。(C)2013 Elsevier Inc.保留所有权利。
Integrin-linked kinase (ILK) is a multifunctional serine/threonine kinase. Accumulating evidences suggest that ILK are involved in cell-matrix interactions, cell proliferation, invasion, migration, angiogenesis and Epithelial-mesenchymal transition (EMT). However, the underlying mechanisms remain largely unknown. EMT has been postulated as a prerequisite for metastasis. The reports have demonstrated that EMT was implicated in metastasis of oral squamous cell carcinomas. Therefore, here we further postulate that ILK might participate in EMT of tongue cancer. We showed that ILK siRNA inhibited EMT with low N-cadherin, Vimentin, Snail, Slug and Twist as well as high E-cadherin expression in vivo and in vitro. We found that knockdown of ILK inhibited cell proliferation, migration and invasion as well as changed cell morphology. We also demonstrated that ILK siRNA inhibited phosphorylation of downstream signaling targets Akt and GSK3 beta as well as reduced expression of MMP2 and MMP9. Furthermore, we found that the tongue tumor with high metastasis capability showed higher ILK, Vimentin, Snail, Slug and Twist as well as lower E-cadherin expression in clinical specimens. Finally, ILK siRNA led to the suppression for tumorigenesis and metastasis in vivo. Our findings suggest that ILK could be a novel diagnostic and therapeutic target for tongue cancer. (C) 2013 Elsevier Inc. All rights reserved.