cPLA2α activates PI3K/AKT and inhibits Smad2/3 during epithelial-mesenchymal transition of hepatocellular carcinoma cells
cPLA2α activates PI3K/AKT and inhibits Smad2/3 during epithelial-mesenchymal transition of hepatocellular carcinoma cells
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cPLA2α在肝癌细胞上皮间质转化过程中激活PI3K/AKT并抑制Smad2/3
DOI：
10.1016/j.canlet.2017.06.022
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发表时间：
2017-09-10
期刊：
影响因子：
9.7
通讯作者：
Guo, Hua
中科院分区：
文献类型：
--
作者：
Fu, Hui;He, Yuchao;Guo, Hua
胞浆磷脂酶A2 α（cPLA 2 α）是调节脂质代谢的关键磷脂酶，在肿瘤进展中起重要作用。在目前的肝细胞癌（HCC）研究中，cPLA 2 α在高转移性HCC细胞系中过表达。免疫组化染色显示cPLA 2 α在HCC的浸润边缘水平升高，对111例患者样本的临床病理分析显示其表达水平与微血管浸润和肝硬化有关。cPLA 2 α的敲低抑制迁移，可能是由于其在肌动蛋白聚合中的作用。过表达cPLA 2 α可促进细胞迁移和侵袭。基于上述机制分析，我们的数据表明cPLA 2 α通过PI 3 K/AKT/ERK途径介导表皮生长因子（EGF）诱导上皮-间充质转化（EMT）。cPLA 2 α活性是转化生长因子（TGF）-β诱导的EMT所必需的。然而，cPLA 2 α抑制Smad 2/3活化并促进PI 3 K/AKT/ERK通路的活化。异种移植肿瘤移植模型证实了cPLA 2 α在HCC侵袭和转移中的作用。基于机制分析，cPLA 2 α介导EGF和TGF-β诱导的EMT，这是HCC转移所必需的。cPLA 2 α是HCC新疗法的潜在靶点。(C)2017爱思唯尔B. V.保留所有权利。
Cytosolic phospholipase A2 alpha (cPLA2 alpha), a key phospholipase that regulates lipid metabolism, plays an important role in tumor progression. In the present study of hepatocellular carcinoma (HCC), cPLA2 alpha was overexpressed in highly metastatic HCC cell lines. Immunohistochemical staining showed increased levels of cPLA2 alpha at the invasive edges of HCC, and a clinicopathological analysis of samples from 111 patients revealed that its expression level was linked with micro-vascular invasion and cirrhosis. Knockdown of cPLA2 alpha inhibited migration, probably due to its role in actin polymerization. Overexpression of cPLA2 alpha promoted cell migration and invasion. Based on the mechanistic analysis, our data suggested that cPLA2 alpha mediate epidermal growth factor (EGF) induced epithelial-mesenchymal transition (EMT) through PI3K/AKT/ERK pathway. cPLA2 alpha activity was required for the transforming growth factor-(TGF)-beta-induced EMT. However, cPLA2 alpha inhibited Smad2/3 activation and promoted the activation of the PI3K/AKT/ERK pathway. A xenograft tumor transplant model confirmed the role of cPLA2 alpha in HCC invasion and metastasis. Based on the mechanistic analysis, cPLA2 alpha mediated both EGF- and TGF-beta-induced EMT, which are essential for HCC metastasis. cPLA2 alpha is a potentially target for novel therapies of HCC. (C) 2017 Elsevier B.V. All rights reserved.