ALX1 Induces Snail Expression to Promote Epithelial-to-Mesenchymal Transition and Invasion of Ovarian Cancer Cells
ALX1 Induces Snail Expression to Promote Epithelial-to-Mesenchymal Transition and Invasion of Ovarian Cancer Cells
复制标题
DOI：
10.1158/0008-5472.can-12-2377
复制
发表时间：
2013-03-01
期刊：
影响因子：
11.2
通讯作者：
Senga, Takeshi
中科院分区：
文献类型：
--
作者：
Yuan, Hong;Kajiyama, Hiroaki;Senga, Takeshi
卵巢癌是一种高度侵袭性和转移性疾病，如果在晚期诊断，预后很差，这种情况经常发生。最近的研究认为，卵巢癌细胞经过上皮-间质转化（EMT）获得侵袭性恶性特性，但在这种情况下相关的分子机制尚不清楚。在这里，我们报告了siRNA筛选的结果，发现同源盒转录因子ALX1是EMT的一种新的调节因子。RNA干扰介导的ALX1表达衰减恢复卵巢癌细胞中E-cadherin表达和细胞-细胞连接形成，抑制细胞侵袭、不依赖锚定生长和肿瘤形成。相反，在卵巢癌细胞或非致瘤性上皮细胞中强制表达ALX1可诱导EMT。我们发现ALX1上调EMT关键调控因子Snail （SNAI1）的表达，并介导了ALX1的EMT激活和细胞侵袭。我们的研究结果将ALX1/Snail轴定义为一种介导癌症侵袭的新型EMT途径。癌症Res;73 (5);1581 - 90。(c) 2012年aacr。
Ovarian cancer is a highly invasive and metastatic disease with a poor prognosis if diagnosed at an advanced stage, which is often the case. Recent studies argue that ovarian cancer cells that have undergone epithelial-to-mesenchymal transition (EMT) acquire aggressive malignant properties, but the relevant molecular mechanisms in this setting are not well-understood. Here, we report findings from an siRNA screen that identified the homeobox transcription factor ALX1 as a novel regulator of EMT. RNA interference-mediated attenuation of ALX1 expression restored E-cadherin expression and cell-cell junction formation in ovarian cancer cells, suppressing cell invasion, anchorage-independent growth, and tumor formation. Conversely, enforced expression of ALX1 in ovarian cancer cells or nontumorigenic epithelial cells induced EMT. We found that ALX1 upregulated expression of the key EMT regulator Snail (SNAI1) and that it mediated EMT activation and cell invasion by ALX1. Our results define the ALX1/Snail axis as a novel EMT pathway that mediates cancer invasion. Cancer Res; 73(5); 1581-90. (C) 2012 AACR.