Enolase 1 differentially contributes to cell transformation in lung cancer but not in esophageal cancer
Enolase 1 differentially contributes to cell transformation in lung cancer but not in esophageal cancer
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DOI：
10.3892/ol.2020.11427
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发表时间：
2020-04-01
期刊：
影响因子：
2.9
通讯作者：
Yu, Chang-Tze Ricky
中科院分区：
文献类型：
--
作者：
Chen, Jo-Mei Maureen;Chiu, Shao-Chih;Yu, Chang-Tze Ricky
烯醇化酶在糖酵解过程中将2-磷酸-D-甘油酸转化为磷酸烯醇丙酮酸。人烯醇化酶（ENO）家族包括三个成员，称为ENO 3，其仅限于肌肉组织，ENO 2，其是神经元和神经内分泌组织特异性的，以及ENO 1，其在几乎所有组织中表达。ENO 1参与多种类型的人类癌症，包括视网膜母细胞瘤、肝细胞癌、胰腺癌、肾细胞癌、胆管癌和胃癌。此外，ENO 1在许多癌细胞系中增强细胞转化。据报道，ENO 1参与了多种对细胞转化有害的活动，包括细胞凋亡和分化。然而，一些研究表明，ENO 1可以在各种类型的肺癌中下调或上调，这表明ENO 1在肺癌的发展中具有不明确的作用。本研究的目的是研究ENO 1对不同类型癌症的不同影响，特别是阐明ENO 1在肺癌中的作用。Western blotting检测肺癌和食管癌组织中ENO 1蛋白的表达水平。此外，外源性ENO 1过表达的细胞系来源于各种组织和单细胞增殖，流式细胞仪分析，并进行蛋白质印迹法，以确定细胞增殖率，细胞转化状态，细胞周期进程和细胞周期调控因子的表达，如细胞周期蛋白和细胞周期蛋白依赖性激酶，和生存因子，如MAPK和AKT。结果表明，ENO 1在收集的肺癌组织组中上调，但在食管癌组织中不上调。此外，异位ENO 1的过表达促进了肺癌细胞系中的细胞增殖和存活，而在其他细胞（包括食管细胞系）中并非如此。此外，机制分析显示，ENO 1通过加速G（1）进展和上调G（1）期细胞周期蛋白依赖性激酶6（CDK 6）来增强细胞增殖，并通过上调MAPK级联中的p38和增加AKT级联中的p-AKT来改善细胞存活，特别是在肺癌细胞系中。总的来说，本研究的结果表明，ENO 1可能有助于肺癌的发展，但不是食管癌。
Enolase transforms 2-phospho-D-glycerate into phosphoenolpyruvate during glycolysis. The human enolase (ENO) family comprises three members named ENO3, which is restricted to muscle tissues, ENO2, which is neuron- and neuroendocrine tissue-specific, and ENO1, which is expressed in almost all tissues. ENO1 is involved in various types of human cancer, including retinoblastoma, hepatocellular carcinoma, pancreatic cancer, renal cell carcinoma, cholangiocarcinoma and gastric cancer. Furthermore, ENO1 enhances cell transformation in numerous cancer cell lines. It has been reported that ENO1 is involved in various activities that are detrimental to cell transformation, including apoptosis and differentiation. However, a few studies demonstrated that ENO1 can be down- or upregulated in various types of lung cancer, which suggests that ENO1 has an ambiguous role in the development of lung cancer. The present study aimed to investigate the differential influences of ENO1 on various types of cancer, and to clarify the role of ENO1 in lung cancer in particular. Western blotting was performed to assess ENO1 protein expression levels in lung cancer and esophageal cancer tissues. Furthermore, exogenous ENO1 was overexpressed in cell lines derived from various tissues and single cell proliferation, flowcytometric analysis, and western blotting were performed to determine the cell proliferation rate, cell transformation status, cell cycle progression and the expression of cell cycle regulators, such as cyclins and cyclin-dependent kinases, and survival factors, such as MAPK and AKT. The results demonstrated that ENO1 was upregulated in collected panels of lung cancer tissues, but not in esophageal cancer tissues. In addition, overexpression of ectopic ENO1 promoted cell proliferation and survival in lung cancer cell lines, which was not the case in other cells, including an esophageal cell line. Furthermore, mechanistic analyses revealed that ENO1 enhanced cell proliferation by accelerating G(1) progression and upregulating G(1) phase cyclin-dependent kinase 6 (CDK6), and improved cell survival by upregulating p38 in the MAPK cascade and increasing p-AKT in the AKT cascade, in particular in lung cancer cell lines. Overall, the results from the present study demonstrated that ENO1 may contribute to the development of lung cancers, but not esophageal cancers.