Isoprenaline induces epithelial-mesenchymal transition in gastric cancer cells
Isoprenaline induces epithelial-mesenchymal transition in gastric cancer cells
复制标题
异丙肾上腺素诱导胃癌细胞上皮间质转化
DOI：
10.1007/s11010-015-2477-0
复制
发表时间：
2015-10-01
影响因子：
4.3
通讯作者：
Wei, Bo
中科院分区：
文献类型：
--
作者：
Lu, Yan-Jie;Geng, Zhi-Jun;Wei, Bo
应激相关信号在调节癌症发展和进展中的新兴作用已被认识到。然而，应激是否作为促进胃癌转移的机制尚不清楚。在这里，我们发现β 2-AR激动剂异丙肾上腺素上调胃癌细胞中CD 44和CD 44 v8 -10的表达水平。CD 44是一种肿瘤干细胞相关的标志物，在胃癌组织中高水平表达，其与体内和体外上皮间质转化（EMT）相关表型的发生密切相关。结合对两种人胃癌细胞系的实验观察，我们发现β（2）-AR信号可以启动EMT。它导致间充质标志物，如α-SMA，波形蛋白和蜗牛在mRNA和蛋白质水平的表达增加，相反，上皮标志物，E-钙粘蛋白和β-连环蛋白的表达减少。β 2-AR受体的异丙肾上腺素刺激激活下游靶点STAT 3，其作为正调节剂发挥作用并介导胃癌细胞中向间充质细胞类型的表型转换。我们的数据提供了一个复杂的信号级联机制的理解，涉及压力相关激素及其对EMT的影响。根据我们的观察，靶向β（2）-AR-STAT 3信号传导的药物干预可能用于改善应激对胃癌发生和进展的影响。
The emerging role of stress-related signaling in regulating cancer development and progression has been recognized. However, whether stress serves as a mechanism to promote gastric cancer metastasis is not clear. Here, we show that the beta(2)-AR agonist, isoprenaline, upregulates expression levels of CD44 and CD44v8-10 in gastric cancer cells. CD44, a cancer stem cell-related marker, is expressed at high levels in gastric cancer tissues, which strongly correlates with the occurrence of epithelial-mesenchymal transition (EMT)-associated phenotypes both in vivo and in vitro. Combined with experimental observations in two human gastric cancer cell lines, we found that beta(2)-AR signaling can initiate EMT. It led to an increased expression of mesenchymal markers, such as alpha-SMA, vimentin, and snail at mRNA and protein levels, and conversely a decrease in epithelial markers, E-cadherin and beta-catenin. Isoprenaline stimulation of beta 2-AR receptors activates the downstream target STAT3, which functions as a positive regulator and mediated the phenotypic switch toward a mesenchymal cell type in gastric cancer cells. Our data provide a mechanistic understanding of the complex signaling cascades involving stress-related hormones and their effects on EMT. In light of our observations, pharmacological interventions targeting beta(2)-AR-STAT3 signaling can potentially be used to ameliorate stress-associated influences on gastric cancer development and progression.