Knockdown of astrocyte elevated gene-1 (AEG-1) in cervical cancer cells decreases their invasiveness, epithelial to mesenchymal transition, and chemoresistance
Knockdown of astrocyte elevated gene-1 (AEG-1) in cervical cancer cells decreases their invasiveness, epithelial to mesenchymal transition, and chemoresistance
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DOI：
10.4161/cc.28607
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发表时间：
2014-06-01
期刊：
影响因子：
4.3
通讯作者：
Zhang, Ying
中科院分区：
文献类型：
--
作者：
Liu, Xiangwen;Wang, Degui;Zhang, Ying
在肿瘤发生发展过程中，上皮-间充质转化(EMT)促进了肿瘤的扩散和转移，其特征是从上皮细胞到成纤维细胞样细胞的形态变化，细胞间连接的解体和细胞运动的增加。星形胶质细胞上调基因-1(AEG-1)在多种肿瘤细胞系和肿瘤中的过度表达被发现与肿瘤的侵袭性行为有关。我们发现AEG-1在低分化宫颈癌组织中的表达升高。然而，目前对AEG-1‘S在肿瘤侵袭转移中的确切作用知之甚少。在这里，我们证明了RNAi下调AEG-1显著减少了宫颈癌细胞的侵袭和迁移，提示AEG-1的过表达可能通过诱导EMT来增强癌细胞的运动能力。AEG-1的下调还导致HeLa细胞间充质标志物Vimentin和转录因子Snail的表达减少，而上皮性标志物E-cadherin的表达上调。此外，在体外，AEG-1基因的敲除减少了集落形成单位，并增加了对癌症药物的敏感性。综上所述，我们的结果表明，AEG-1的敲除可以减少宫颈癌细胞的EMT和化疗耐药性，并减弱其侵袭行为。
During cancer development, epithelial-mesenchymal transition (EMT) facilitates tumor dissemination and metastatic spread, which is characterized by morphologic changes from epithelial cells to fibroblast-like cells, disassembly of intercellular junction, and increased cell motility. Overexpression of astrocyte elevated gene-1(AEG-1) in various cancer cell lines and cancers has been found to be associated with aggressive tumor behavior. We found that AEG-1 expression was elevated in low differentiation cervical cancer specimens from patients. However, little is known about the AEG-1's precise role in invasion and metastasis. Here we demonstrate that downregulation of AEG-1 by RNAi significantly decreased the invasion and migration of cervical cancer cells, suggesting that AEG-1 overexpression may enhance cancer cell motility by inducing EMT. Downregulation of AEG-1 also led to reduced expression of mesenchymal marker vimentin and the transcription factor Snail but upregulation of epithelial marker E-cadherin in HeLa cells. In addition, knockdown of AEG-1 decreased colony forming units and increased sensitivity to cancer drugs in vitro. Taken together, our results suggest that knockdown of AEG-1 could decrease EMT and chemoresistance in cervical cancer cells and attenuate their aggressive behavior.