Downregulation of HADH promotes gastric cancer progression via Akt signaling pathway.
Downregulation of HADH promotes gastric cancer progression via Akt signaling pathway.
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HADH下调通过Akt信号通路促进胃癌进展
DOI：
10.18632/oncotarget.19348
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发表时间：
2017-09-29
期刊：
影响因子：
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通讯作者：
Zhou J
中科院分区：
文献类型：
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作者：
Shen C;Song YH;Xie Y;Wang X;Wang Y;Wang C;Liu S;Xue SL;Li Y;Liu B;Tang Z;Chen W;Song J;Amin HM;Zhou J
HADH是脂肪酸氧化的关键酶。本研究的目的是确定HADH在胃癌中的作用。我们分析了HADH在102对胃癌标本中的表达。Western blot分析显示，HADH在I/II期胃癌样品中与匹配的邻近正常胃组织相比降低，并且其表达在III/IV期样品中进一步降低。重要的是，在胃癌肿瘤样品中，HADH的表达减少与p-Akt的表达增加和PTEN的表达减少相关。为了确定HADH下调在胃癌进展中的意义，我们使用transwell测定法测试了HADH敲低或过表达对胃癌细胞迁移和侵袭的影响。HADH基因敲低可显著促进胃癌细胞的迁移和侵袭，这与p-Akt表达增加有关。PI 3 K抑制剂LY 294002可抑制HADH shRNA诱导的细胞迁移/侵袭，并消除p-Akt的上调。相反，HADH过表达抑制MKN 45细胞的迁移和侵袭。在此，我们首次证明HADH的下调通过激活Akt信号通路促进胃癌的进展。
HADH is a key enzyme in fatty acid oxidation. The aim of this study was to identify the role of HADH in gastric cancer. We analyzed the expression of HADH in 102 pairs of gastric cancer samples. Western blot analysis revealed that HADH was decreased in stage I/II gastric cancer samples compared to matched adjacent normal gastric tissue, and its expression was further decreased in stage III/IV samples. Importantly, the reduced expression of HADH was associated with increased expression of p-Akt and reduced expression of PTEN in the gastric carcinoma tumor samples. To determine the significance of HADH downregulation in gastric cancer progression, we tested the impact of HADH knockdown or overexpression on the migration and invasion of the gastric cancer cells using a transwell assay. Knockdown of HADH significantly promoted gastric cancer cell migration and invasion, which was associated with increased expression of p-Akt. The PI3K inhibitor LY294002 inhibited HADH shRNA induced migration/invasion, and abolished the upregulation of p-Akt. By contrast, HADH overexpression inhibited the migration and invasion of MKN45 cells. Herein, for the first time, we demonstrate that downregulation of HADH promotes gastric cancer progression via activation of Akt signaling pathway.