Androgen receptor enhances cell adhesion and decreases cell migration via modulating β1-integrin-AKT signaling in hepatocellular carcinoma cells
Androgen receptor enhances cell adhesion and decreases cell migration via modulating β1-integrin-AKT signaling in hepatocellular carcinoma cells
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DOI：
10.1016/j.canlet.2014.05.017
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发表时间：
2014-08-28
期刊：
影响因子：
9.7
通讯作者：
Chang, Chawnshang
中科院分区：
文献类型：
--
作者：
Ma, Wen-Lung;Jeng, Long-Bin;Chang, Chawnshang
雄激素受体（AR）已被证明在疾病过程的早期阶段促进肝细胞癌（HCC）的发生和发展，并在疾病的晚期阶段抑制HCC细胞的侵袭。管理这些双重但相反的作用的机制尚未阐明。使用致癌物诱导的HCC体内小鼠模型和体外人HCC细胞系SKhep 1，我们发现，与野生型小鼠细胞相比，原代HCC细胞中AR的敲除导致HCC细胞粘着斑能力降低。将功能性AR加入人HCC SKhep 1细胞后获得了类似的结果。进一步的分析表明，AR在HCC细胞粘附中的作用至少部分地由其上调β 1-整合素和激活PI 3 K/AKT通路的能力所控制。我们还发现AR-β 1-整联蛋白介导的细胞粘附抑制细胞迁移。这些结果表明，AR-β 1-整合素-PI 3 K/AKT信号通路可能在AR对细胞粘附和迁移的细胞水平的双峰功能中发挥作用。(C)2014爱思唯尔爱尔兰有限公司版权所有。
The androgen receptor (AR) has been shown to promote the initiation and development of hepatocellular carcinoma (HCC) during the early stage of the disease process and to suppress HCC cell invasion during the later stages of the disease. The mechanisms governing these dual yet opposite roles have yet to be elucidated. Using carcinogen-induced HCC in vivo mouse models and the in vitro human HCC cell line SKhep1, we found that knockout of AR in primary HCC cells led to a decrease in HCC cell focal adhesion capacity compared to cells from wildtype mice. Similar results were obtained after adding functional AR into human HCC SKhep1 cells. Further analysis revealed that the role AR plays in adhesion of HCC cells is governed, at least in part, by its ability to up-regulate beta 1-integrin and activate the PI3K/AKT pathway. We also found that AR-beta 1-integrin-mediated cell adhesion suppresses cell migration. Those findings indicate that the AR-beta 1-integrin-PI3K/AKT signaling pathway might play a role in the bimodal function of AR on cell adhesion and migration at the cellular level. (C) 2014 Elsevier Ireland Ltd. All rights reserved.