High throughput proteomic and metabolic profiling identified target correction of metabolic abnormalities as a novel therapeutic approach in head and neck paraganglioma.
High throughput proteomic and metabolic profiling identified target correction of metabolic abnormalities as a novel therapeutic approach in head and neck paraganglioma.
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高通量蛋白质组学和代谢分析确定了代谢异常的目标校正作为头颈部副神经节瘤的一种新型治疗方法。
DOI：
10.1016/j.tranon.2021.101146
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发表时间：
2021-08
影响因子：
5
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Wang Z;Chen H;Xue L;He W;Shu W;Wu H;Wang Z
SDH突变导致头部和颈部paragangliomas（HNPGLS）的发生。
与代谢相关的氧化磷酸化（ROS）的放松管制可能在HNPGL中起重要作用。
NDUFA 2、4和10显示了HNPGL中最显着的脱甲，并且可以通过二甲双胍校正该放松管制。
二甲双胍通过降低的活性氧和代谢改变了对HNPGL细胞的抑制作用。
HNPGL的蛋白质组学/代谢分析确定ROS/代谢作为治疗靶点在临床环境中的作用。
颈部和颈部的肿瘤是罕见的肿瘤，代表了编码琥珀酸酯脱氢酶（SDH）的生殖器突变的困难治疗范式。基因突变。在这些患者中，蛋白质在具有SDHB突变的肿瘤中损失了paraganglioma瘤细胞系（PGL-626）确认了氧化酶的高水平。 HNPGL中的磷酸化和代谢途径。线粒体复合物亚基NDUFA2，NDUFA10和NDUFA4表达最显着增加，并且主要在PGL-626细胞的细胞中局部局部局部。 - NDUFA2、4和10的调节，显着下降反应性氧和线粒体膜电位的水平。 PGL肿瘤发生和确定目标纠正代谢异常是该疾病的一种新型治疗方法。
SDH mutations are responsible for the occurrence of head and neck paragangliomas (HNPGLs). Deregulation of oxidative phosphorylation (ROS) in association with metabolism may play an important role in HNPGLs. NDUFA 2, 4 and 10 showed the most significant deregulaion in HNPGLs, and this deregulation can be corrected by metformin. Metformin exerts inhibitory effects on HNPGL cells via reduced level of reactive oxygen species and altered metabolism. Proteomic/metabolic profiling of HNPGLs identifies the role of ROS/metabolism as a therapeutic target in clinical settings. Head and neck paragangliomas (HNPGLs) are rare neoplasms that represent difficult treatment paradigms in neurotology. Germline mutations in genes encoding succinate dehydrogenase (SDH) are the cause of nearly all familial HNPGLs. However, the molecular mechanisms underlying tumorigenesis remain unclear. Mutational analysis identified 6 out of 14 HNPGLs harboring clinicopathologic SDH gene mutations. The SDHB gene was most frequently mutated in these patients, and western blot showed loss of SDHB protein in tumors with SDHB mutations. The paraganglioma cell line (PGL-626) was established from a sample that harbored a missense SDHB mutation (c.649C > T). Spectrometric analysis using tandem mass tags identified 151 proteins significantly differentially expressed in HNPGLs compared with normal nerves. Bioinformatics analyses confirmed the high level of enrichment of oxidative phosphorylation and metabolism pathways in HNPGLs. The mitochondrial complex subunits NDUFA2, NDUFA10, and NDUFA4, showed the most significantly increased expression and were localized predominantly in the cytoplasm of PGL-626 cells. The mitochondrial complex I inhibitor metformin exerted dose-dependent inhibitory effects on PGL-626 cells via cooperative down-regulation of NDUFA2, 4, and 10, with a significant decrease in the levels of reactive oxygen species and mitochondrial membrane potential. Further metabolomic analysis of PGL-626 cells showed that metabolites involved in central carbon metabolism in cancer and sphingolipid signaling pathways, pantothenate and CoA biosynthesis, and tryptophan and carbon metabolism were significantly altered after metformin treatment. Thus, this study provides insights into the molecular mechanisms underlying HNPGL tumorigenesis and identifies target correction of metabolic abnormalities as a novel therapeutic approach for this disease.
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影响因子：
29
作者：
Liu X;Romero IL;Litchfield LM;Lengyel E;Locasale JW
通讯作者：
Locasale JW
影响因子：
50.3
作者：
Fishbein L;Leshchiner I;Walter V;Danilova L;Robertson AG;Johnson AR;Lichtenberg TM;Murray BA;Ghayee HK;Else T;Ling S;Jefferys SR;de Cubas AA;Wenz B;Korpershoek E;Amelio AL;Makowski L;Rathmell WK;Gimenez-Roqueplo AP;Giordano TJ;Asa SL;Tischler AS;Cancer Genome Atlas Research Network;Pacak K;Nathanson KL;Wilkerson MD
通讯作者：
Wilkerson MD
头颈副神经节瘤患者的遗传和表观遗传模式与不同的临床特征相关
DOI：
10.1007/s00432-017-2355-0
发表时间：
2017-06-01
影响因子：
3.6
作者：
Chen, Hongsai;Zhu, Weidong;Wu, Hao
通讯作者：
Wu, Hao
影响因子：
--
作者：
Hes FJ;Weiss MM;Woortman SA;de Miranda NF;van Bunderen PA;Bonsing BA;Stokkel MP;Morreau H;Romijn JA;Jansen JC;Vriends AH;Bayley JP;Corssmit EP
通讯作者：
Corssmit EP
影响因子：
4.8
作者：
Imperiale, Alessio;Moussallieh, Franois-Marie;Roche, Philippe;Battini, Stephanie;Cicek, A. Ercument;Sebag, Frederic;Brunaud, Laurent;Barlier, Anne;Elbayed, Karim;Loundou, Anderson;Bachellier, Philippe;Goichot, Bernard;Stratakis, Constantine A.;Pacak, Karel;Namer, Izzie-Jacques;Taieb, david
通讯作者：
Taieb, david