UPLC-MS-based metabolomics reveals metabolic dysregulation in ALDH1A1-overexpressed lung adenocarcinoma cells
UPLC-MS-based metabolomics reveals metabolic dysregulation in ALDH1A1-overexpressed lung adenocarcinoma cells
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DOI：
10.1007/s11306-019-1514-5
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发表时间：
2019-03
期刊：
影响因子：
3.6
通讯作者：
Tang Ya Bin
中科院分区：
文献类型：
--
作者：
Wang Yang;Wang Cong Hui;Zhang Yu Fei;Zhu Liang;Lei Hui Min;Tang Ya Bin
特定的癌基因型可以在癌症中产生不同的代谢变化。近年来，代谢重编程被认为是耐药的重要原因。乙醛脱氢酶1A 1（ALDH 1A 1）在耐药肺腺癌中过表达，可能是获得性耐药的原因。然而，在这方面，ALDH 1A 1对肺腺癌细胞代谢的影响尚不清楚。为了更好地了解ALDH 1A 1诱导肺腺癌细胞耐药的重编程和代谢机制，我们试图研究ALDH 1A 1诱导肺腺癌细胞代谢的改变。方法采用超高效液相色谱-四极杆时间-质谱联用技术分析肺腺癌HCC 827-ALDH 1A 1细胞代谢的改变。飞行质谱（UPLC-QTOF-MS）。通过单变量和多变量统计分析提取HCC 827-ALDH 1A 1代谢特征。结果用标准品鉴定出22种代谢产物，包括尿苷一磷酸（UMP）、尿苷二磷酸（UDP）、腺苷二磷酸（ADP）、苹果酸、丙二酰辅酶A、烟酰胺腺嘌呤二核苷酸（NAD）、辅酶A等。代谢途径分析揭示了HCC 827-ALDH 1A 1细胞中的几个异常代谢途径，包括核苷酸代谢、尿素循环、三羧酸（TCA）循环和甘油磷脂代谢等。几乎所有患者最终都会因获得性耐药而发生疾病进展。需要确定生物获得性抗性的机制。我们的研究确定了HCC 827-ALDH 1A 1细胞中改变的代谢物，增强了我们对ALDH 1A 1诱导的肺腺癌代谢改变的认识，创造了一种新的治疗途径。这些ALDH 1A 1过表达的代谢特征可能揭示耐药肿瘤的分子机制和候选药物靶点。此外，新的分子靶点可能为肺癌治疗的潜在抗癌策略提供基础。
IntroductionSpecific oncogenotypes can produce distinct metabolic changes in cancer. Recently it is considered that metabolic reprograming contributes heavily to drug resistance. Aldehyde dehydrogenase 1A1 (ALDH1A1), is overexpressed in drug resistant lung adenocarcinomas and may be the cause of acquired drug resistance. However, how ALDH1A1 affects metabolic profiling in lung adenocarcinoma cells remains elusive.ObjectiveWe sought to investigate metabolic alterations induced by ALDH1A1 in lung adenocarcinoma in order to better understand the reprogramming and metabolic mechanism of resistance induced by ALDH1A1.MethodsMetabolic alterations in lung adenocarcinoma HCC827-ALDH1A1 cells were analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC–QTOF-MS). HCC827-ALDH1A1 metabolic signatures were extracted by univariate and multivariate statistical analysis. Furthermore, metabolite enrichment analysis and pathway analysis were performed using MetaboAnalyst 4.0 software.ResultsTwenty-two metabolites were positively identified using authentic standards, including uridine monophosphate (UMP), uridine diphosphate (UDP), adenosine diphosphate (ADP), malic acid, malonyl-coenzyme A, nicotinamide adenine dinucleotide (NAD), coenzyme A and so on. Furthermore, metabolic pathway analysis revealed several dysregulated pathways in HCC827-ALDH1A1 cells, including nucleotide metabolism, urea cycle, tricarboxylic acid (TCA) cycle, and glycerol phospholipid metabolism etc.ConclusionLung cancer is the most frequent cause of cancer-related deaths worldwide. Nearly all patients eventually undergo disease progression due to acquired resistance. Mechanisms of biological acquired resistance need to be identified. Our study identified altered metabolites in HCC827-ALDH1A1 cells, enhancing our knowledge of lung adenocarcinoma metabolic alterations induced by ALDH1A1, creating a novel therapeutic pathway. These metabolic signatures of ALDH1A1 overexpression may shed light on molecular mechanisms in drug-resistant tumors, and on candidate drug targets. Furthermore, new molecular targets may provide the foundation for potential anticancer strategies for lung cancer therapy.
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影响因子：
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作者：
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通讯作者：
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