研究动态
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非小细胞肺癌中核因子κB的表达。

Nuclear factor kappa B expression in non-small cell lung cancer.

发表日期:2023 Sep 14
作者: Leilei Zhang, Claudia M Ludden, Alexander J Cullen, Kenneth D Tew, André Luís Branco de Barros, Danyelle M Townsend
来源: BIOMEDICINE & PHARMACOTHERAPY

摘要:

在这篇小综述中,我们讨论了NF-κB这一促炎性转录因子在参与炎症、增殖和凋亡途径的基因表达中的作用,并将其与不同人类癌症,尤其是非小细胞肺癌(NSCLC)的预后相关起来。我们及其他人的研究表明,NF-κB的活性可以通过翻译后的S-谷胱甘肽化作用受到影响,通过其半胱氨酸残基与谷胱甘肽(GSH)之间可逆形成的混合二硫键形式。临床数据分析显示,NF-κB的高表达与NSCLC患者的总生存期(OS)缩短相关,表明NF-κB可能具有肿瘤促进功能。此外,NF-κB的表达与肿瘤分期、淋巴结转移和这些患者的5年生存率相关。与相邻正常组织相比,NF-κB在肿瘤组织的细胞质中过度表达。NF-κB的S-谷胱甘肽化作用通过干扰NF-κB亚单位的DNA结合活性,导致NF-κB的负调控。对氧化剂的应答中,NF-κB的S-谷胱甘肽化还与肺部炎症的增强相关。因此,S-谷胱甘肽化是NF-κB调控的重要因素,临床结果突显了NF-κB在NSCLC中的重要性,该疾病中NF-κB水平与不良预后相关。版权所有© 2023作者。由Elsevier Masson SAS出版。保留所有权利。
In this mini-review, we discuss the role of NF-κB, a proinflammatory transcription factor, in the expression of genes involved in inflammation, proliferation, and apoptosis pathways, and link it with prognosis of various human cancers, particularly non-small cell lung cancer (NSCLC). We and others have shown that NF-κB activity can be impacted by post-translational S-glutathionylation through reversible formation of a mixed disulfide bond between its cysteine residues and glutathione (GSH). Clinical data analysis showed that high expression of NF-κB correlated with shorter overall survival (OS) in NSCLC patients, suggesting a tumor promotion function for NF-κB. Moreover, NF-κB expression was associated with tumor stage, lymph node metastasis, and 5-year OS in these patients. NF-κB was over-expressed in the cytoplasm of tumor tissue compared to adjacent normal tissues. S-glutathionylation of NF-κB caused negative regulation by interfering with DNA binding activities of NF-κB subunits. In response to oxidants, S-glutathionylation of NF-κB also correlated with enhanced lung inflammation. Thus, S-glutathionylation is an important contributor to NF-κB regulation and clinical results highlight the importance of NF-κB in NSCLC, where NF-κB levels are associated with unfavorable prognosis.Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.