Nuclear factor kappa B expression in non-small cell lung cancer
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 h...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-11-01
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| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S075333222301257X |
| _version_ | 1797660580399546368 |
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| author | Leilei Zhang Claudia M. Ludden Alexander J. Cullen Kenneth D. Tew André Luís Branco de Barros Danyelle M. Townsend |
| author_facet | Leilei Zhang Claudia M. Ludden Alexander J. Cullen Kenneth D. Tew André Luís Branco de Barros Danyelle M. Townsend |
| author_sort | Leilei Zhang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T18:31:57Z |
| format | Article |
| id | doaj.art-6a59c99872434363a3b346b863248ec3 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-11T18:31:57Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-6a59c99872434363a3b346b863248ec32023-10-13T11:02:41ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-11-01167115459Nuclear factor kappa B expression in non-small cell lung cancerLeilei Zhang0Claudia M. Ludden1Alexander J. Cullen2Kenneth D. Tew3André Luís Branco de Barros4Danyelle M. Townsend5Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC, USADepartment of Drug Discovery and Experimental Sciences, Medical University of South Carolina, Charleston, SC, USADepartment of Drug Discovery and Experimental Sciences, Medical University of South Carolina, Charleston, SC, USADepartment of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC, USADepartment of Clinical and Toxicological Analyses, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, BrazilDepartment of Drug Discovery and Experimental Sciences, Medical University of South Carolina, Charleston, SC, USA; Correspondence to: Departments of Pharmaceutical and Biomedical Sciences, Medical University of South Carolina, 173 Ashley Ave., P.O. Box 250505, Charleston, SC 29425, USA.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.http://www.sciencedirect.com/science/article/pii/S075333222301257XNFkBLung cancerP65P50Redox regulationGlutathionylation |
| spellingShingle | Leilei Zhang Claudia M. Ludden Alexander J. Cullen Kenneth D. Tew André Luís Branco de Barros Danyelle M. Townsend Nuclear factor kappa B expression in non-small cell lung cancer Biomedicine & Pharmacotherapy NFkB Lung cancer P65 P50 Redox regulation Glutathionylation |
| title | Nuclear factor kappa B expression in non-small cell lung cancer |
| title_full | Nuclear factor kappa B expression in non-small cell lung cancer |
| title_fullStr | Nuclear factor kappa B expression in non-small cell lung cancer |
| title_full_unstemmed | Nuclear factor kappa B expression in non-small cell lung cancer |
| title_short | Nuclear factor kappa B expression in non-small cell lung cancer |
| title_sort | nuclear factor kappa b expression in non small cell lung cancer |
| topic | NFkB Lung cancer P65 P50 Redox regulation Glutathionylation |
| url | http://www.sciencedirect.com/science/article/pii/S075333222301257X |
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