Overexpression of Aurora-A Enhances Invasion and Matrix Metalloproteinase-2 Expression in Esophageal Squamous Cell Carcinoma Cells
Overexpression of Aurora-A Enhances Invasion and Matrix Metalloproteinase-2 Expression in Esophageal Squamous Cell Carcinoma Cells
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Aurora-A 的过表达增强食管鳞状细胞癌细胞的侵袭和基质金属蛋白酶-2 的表达
DOI：
10.1158/1541-7786.mcr-11-0416
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发表时间：
2012-05-01
影响因子：
5.2
通讯作者：
Cheng, Niuliang
中科院分区：
文献类型：
--
作者：
Wang, Xiaoxia;Lu, Na;Cheng, Niuliang
食管鳞状细胞癌（ESCC）是最具侵袭性的恶性肿瘤之一，转移是ESCC患者死亡的主要原因。已经表明，有丝分裂丝氨酸/苏氨酸激酶Aurora-A的扩增和过表达发生在几种类型的人类肿瘤中，包括ESCC。此外，Aurora-A表达水平的增加已被预测与肿瘤分化和侵袭能力的等级相关。然而，Aurora-A介导其侵袭作用的机制仍然难以捉摸。在这篇文章中，我们发现Aurora-A过表达显着增加细胞的迁移和侵袭以及基质金属蛋白酶-2（MMP-2）的分泌和表达。相反，siRNA介导的Aurora-A在人ESCC细胞中表达的敲低导致细胞侵袭性以及MMP-2的分泌和表达的抑制。此外，Aurora-A过表达增加了p38丝裂原活化蛋白激酶（MAPK）和Akt的磷酸化水平，而siRNA敲低Aurora-A则降低了p38 MAPK和Akt的活性。此外，使用化学抑制剂阻断上述激酶的活性可抑制Aurora-A诱导MMP-2分泌和表达以及细胞侵袭的能力。这些数据表明Aurora-A的过表达通过增强肿瘤细胞侵袭以及MMP-2活性和表达而促进ESCC的恶性发展，这可以通过涉及p38 MAPK和Akt蛋白激酶的信号通路发生。综上所述，这些研究为Aurora-A在ESCC恶性发展中的促进作用提供了分子基础。Mol Cancer Res; 10（5）; 588-96. (C)2012年AACR。
Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers, and metastasis is the principal cause of death in ESCC patients. It has been shown that amplification and overexpression of mitotic serine/threonine kinase Aurora-A occur in several types of human tumors, including ESCC. Moreover, increase in expression levels of Aurora-A has been predicted to correlate with the grades of tumor differentiation and invasive capability. However, the mechanisms by which Aurora-A mediates its invasive effects still remain elusive. In this article, we showed that Aurora-A overexpression significantly increased cell migration and invasion as well as secretion and expression of matrix metalloproteinase-2 (MMP-2). Conversely, siRNA-mediated knockdown of Aurora-A expression in human ESCC cells led to inhibition of cell invasiveness as well as secretion and expression of MMP-2. In addition, Aurora-A overexpression increased phosphorylation levels of p38 mitogen-activated protein kinase (MAPK) and Akt, and the knockdown of Aurora-A by siRNA decreased the activity of p38 MAPK and Akt. Moreover, the blocking of the activity of above kinases using chemical inhibitors suppressed the ability of Aurora-A to induce MMP-2 secretion and expression as well as cell invasion. These data show that overexpression of Aurora-A contributes to the malignancy development of ESCC by enhancing tumor cell invasion as well as MMP-2 activity and expression, which can occur through signaling pathways involving p38 MAPK and Akt protein kinases. Taken together, these studies provide a molecular basis for promoting the role of Aurora-A in malignancy development of ESCC. Mol Cancer Res; 10(5); 588-96. (C) 2012 AACR.