ABHD5在子宫内膜癌中的致癌作用。
Oncogenic role of ABHD5 in endometrial cancer.
作者信息
Zhou Qing, Wang Fang, Zhou Kai, Huang Kate, Zhu Qiuyuan, Luo Xishao, Yu Jiangtao, Shi Zhengzheng
机构信息
Department of Gynecology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China,
Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
出版信息
Cancer Manag Res. 2019 Mar 14;11:2139-2150. doi: 10.2147/CMAR.S188648. eCollection 2019.
BACKGROUND
Abhydrolase domain containing 5 (ABHD5) functions as a tumor suppressor in colorectal and prostate cancers. The aim of this study was to investigate the roles of ABHD5 in endometrial cancer.
MATERIALS AND METHODS
ABHD5 expression was detected in clinical samples by immunohistochemical staining. Cell proliferation and invasion were evaluated with the Cell Counting Kit-8 and Transwell assay, respectively. Western blotting was performed to analyze protein expression. Glucose uptake was assessed by 2-[-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose. Lactate production was detected by a lactate assay kit.
RESULTS
In the present study, ABHD5 was overexpressed in endometrial cancer tissues, and its expression was closely correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage and lymph node metastasis. In addition, we observed that the knockdown of ABHD5 inhibited cell proliferation, invasion, glucose uptake and lactate production in HEC-1A cells, which expressed high levels of ABHD5. Conversely, the opposite effects were observed when ABHD5 was ectopically expressed in Ishikawa cells, which had low levels of ABHD5. Furthermore, the changes in glycolysis regulators (enolase 1 [ENO1], glucose transporter 1 [GLUT1] and lactate dehydrogenase A [LDHA]) and epithelial-to-mesenchymal transition-related proteins (E-cadherin and Snail) in HEC-1A cells with ABHD5 knockdown were consistent with the effects of ABHD5 on glycolysis and cell invasion. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was increased, while the phosphorylated AKT (p-AKT) was decreased when ABHD5 was downregulated. Notably, treatment with the allosteric AKT inhibitor MK-2206 completely abolished the effects caused by ABHD5 overexpression in Ishikawa cells. Finally, ABHD5 knockdown potently suppressed tumor growth in vivo.
CONCLUSION
Overall, these results suggest that ABHD5 may play an oncogenic role in endometrial cancer via the AKT pathway.
背景
含水解酶结构域5（ABHD5）在结直肠癌和前列腺癌中发挥肿瘤抑制作用。本研究旨在探讨ABHD5在子宫内膜癌中的作用。
材料与方法
采用免疫组织化学染色法检测临床样本中ABHD5的表达。分别用细胞计数试剂盒-8和Transwell实验评估细胞增殖和侵袭能力。进行蛋白质免疫印迹分析蛋白表达。用2-[(7-硝基苯并-2-恶唑-1,3-二氮杂环丁烷-4-基)氨基]-2-脱氧葡萄糖评估葡萄糖摄取。用乳酸检测试剂盒检测乳酸生成。
结果
在本研究中，ABHD5在子宫内膜癌组织中过表达，其表达与国际妇产科联盟（FIGO）分期及淋巴结转移密切相关。此外，我们观察到敲低ABHD5可抑制HEC-1A细胞（该细胞ABHD5表达水平高）的增殖、侵袭、葡萄糖摄取和乳酸生成。相反，在ABHD5水平低的Ishikawa细胞中异位表达ABHD5时，观察到相反的效果。此外，敲低ABHD5的HEC-1A细胞中糖酵解调节因子（烯醇化酶1 [ENO1]、葡萄糖转运蛋白1 [GLUT1]和乳酸脱氢酶A [LDHA]）以及上皮-间质转化相关蛋白（E-钙黏蛋白和Snail）的变化与ABHD5对糖酵解和细胞侵袭的影响一致。当ABHD5下调时，第10号染色体缺失的磷酸酶和张力蛋白同源物（PTEN）增加，而磷酸化的AKT（p-AKT）减少。值得注意的是，用变构AKT抑制剂MK-2206处理完全消除了ABHD5过表达在Ishikawa细胞中引起的效应。最后，敲低ABHD5可有效抑制体内肿瘤生长。
结论
总体而言，这些结果表明ABHD5可能通过AKT途径在子宫内膜癌中发挥致癌作用。
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