Neuron specific enolase promotes tumor metastasis by activating the Wnt/β-catenin pathway in small cell lung cancer.

Neuron specific enolase promotes tumor metastasis by activating the Wnt/β-catenin pathway in small cell lung cancer.
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神经元特异性烯醇化酶通过激活小细胞肺癌中的 Wnt/β-catenin 通路促进肿瘤转移

DOI:
10.1016/j.tranon.2021.101039
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发表时间:
2021-04
影响因子:
5
通讯作者:
Liu G
Liu G
中科院分区:
医学3区
文献类型:
--
作者:
Zha Z;Li D;Zhang P;Wang P;Fang X;Liu X;Weng C;Li B;Wu Y;Mao H;Wang L;Xu L;Dong J;Guan M;Lu L;Liu G

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NSE表达与SCLC远处转移呈正相关。NSE促进SCLC细胞的迁移、侵袭和EMT过程。在NSE过表达的SCLC细胞中,Wnt/β-catenin信号通路被激活。NSE与β-catenin相互作用并抑制β-catenin的降解。神经元特异性烯醇化酶(NSE)已被用作小细胞肺癌(SCLC)患者的特异性生物标志物。然而,NSE在小细胞肺癌中的生物学功能和作用机制尚不清楚。在这项研究中,我们阐明了NSE在SCLC进展中的作用,发现NSE表达与远处转移呈正相关。功能分析显示NSE过表达促进SCLC细胞的迁移和侵袭。机制分析表明,NSE过表达诱导SCLC细胞发生上皮-间质转化(EMT)。此外,NSE过表达可增加β-catenin及其下游靶基因的蛋白表达,沉默β-catenin可消除NSE介导的细胞迁移、侵袭和EMT过程。NSE与β-catenin相互作用,抑制β-catenin的降解。此外,动物实验也表明NSE在体内可促进SCLC细胞的EMT进程和远处转移。综上所述,NSE可通过激活Wnt/β-catenin信号通路促进SCLC细胞的EMT进程,从而促进细胞迁移、侵袭和远处转移,这可能成为SCLC治疗的潜在靶点。
NSE expression was positively correlated with distant metastasis of SCLC. NSE promotes migration, invasion and EMT process of SCLC cells. Wnt/β-catenin signaling pathway is activated in the NSE-overexpressing SCLC cells. NSE interacts with β-catenin and inhibits the degradation of β-catenin. Neuron-specific enolase (NSE) has been used as a specific biomarker for small cell lung cancer (SCLC) patients. Nevertheless, the biological function and mechanism of NSE in SCLC are still unclear. In this study, we clarified the role of NSE in the progression of SCLC and found that NSE expression was positively correlated with distant metastasis. Functional analysis showed that overexpression of NSE promoted migration and invasion of SCLC cells. Mechanism analysis showed that NSE overexpression induced epithelial-mesenchymal transition (EMT) of SCLC cells. Moreover, overexpression of NSE increased the protein expression of β-catenin and its downstream target genes, and silencing β-catenin eliminated NSE-mediated cell migration, invasion and EMT process. Furthermore, NSE interacted with β-catenin and inhibited the degradation of β-catenin. Besides, the animal experiments also indicated that NSE could promote the EMT process and distant metastasis of SCLC cells in vivo. In summary, our results revealed that NSE could promote the EMT process of SCLC cells by activating the Wnt/β-catenin signaling pathway, thereby promoting cell migration, invasion and distant metastasis, which might serve as a potential target for the therapy of SCLC patients.
DOI: 10.1172/jci97611
发表时间: 2018-04-02
影响因子: 15.9
作者:
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发表时间: 2000-02-01
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DOI: 10.1016/s0169-5002(00)00186-0
发表时间: 2001-02-01
期刊: LUNG CANCER
影响因子: 5.3
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DOI: 10.1016/j.jtho.2016.01.012
发表时间: 2016-04
期刊: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
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Bunn PA Jr;Minna JD;Augustyn A;Gazdar AF;Ouadah Y;Krasnow MA;Berns A;Brambilla E;Rekhtman N;Massion PP;Niederst M;Peifer M;Yokota J;Govindan R;Poirier JT;Byers LA;Wynes MW;McFadden DG;MacPherson D;Hann CL;Farago AF;Dive C;Teicher BA;Peacock CD;Johnson JE;Cobb MH;Wendel HG;Spigel D;Sage J;Yang P;Pietanza MC;Krug LM;Heymach J;Ujhazy P;Zhou C;Goto K;Dowlati A;Christensen CL;Park K;Einhorn LH;Edelman MJ;Giaccone G;Gerber DE;Salgia R;Owonikoko T;Malik S;Karachaliou N;Gandara DR;Slotman BJ;Blackhall F;Goss G;Thomas R;Rudin CM;Hirsch FR
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DOI: 10.3892/ol.2016.5336
发表时间: 2016-12-01
期刊: ONCOLOGY LETTERS
影响因子: 2.9
作者:
Bae, Woo-Jin;Lee, Sang-Hyuk;Lim, Young-Chang
通讯作者: Lim, Young-Chang