NFE2L2 and STAT3 Converge on Common Targets to Promote Survival of Primary Lymphoma Cells
NFE2L2 and STAT3 are key pro-survival molecules, and thus, their targeting may represent a promising anti-cancer strategy. In this study, we found that a positive feedback loop occurred between them and provided evidence that their concomitant inhibition efficiently impaired the survival of PEL cell...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/14/11598 |
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| author | Andrea Arena Michele Di Crosta Roberta Gonnella Roberta Zarrella Maria Anele Romeo Rossella Benedetti Maria Saveria Gilardini Montani Roberta Santarelli Gabriella D’Orazi Mara Cirone |
| author_facet | Andrea Arena Michele Di Crosta Roberta Gonnella Roberta Zarrella Maria Anele Romeo Rossella Benedetti Maria Saveria Gilardini Montani Roberta Santarelli Gabriella D’Orazi Mara Cirone |
| author_sort | Andrea Arena |
| collection | DOAJ |
| description | NFE2L2 and STAT3 are key pro-survival molecules, and thus, their targeting may represent a promising anti-cancer strategy. In this study, we found that a positive feedback loop occurred between them and provided evidence that their concomitant inhibition efficiently impaired the survival of PEL cells, a rare, aggressive B cell lymphoma associated with the gammaherpesvirus KSHV and often also EBV. At the molecular level, we found that NFE2L2 and STAT3 converged in the regulation of several pro-survival molecules and in the activation of processes essential for the adaption of lymphoma cells to stress. Among those, STAT3 and NFE2L2 promoted the activation of pathways such as MAPK3/1 and MTOR that positively regulate protein synthesis, sustained the antioxidant response, expression of molecules such as MYC, BIRC5, CCND1, and HSP, and allowed DDR execution. The findings of this study suggest that the concomitant inhibition of NFE2L2 and STAT3 may be considered a therapeutic option for the treatment of this lymphoma that poorly responds to chemotherapies. |
| first_indexed | 2024-03-11T00:59:50Z |
| format | Article |
| id | doaj.art-8e717e52ac8e42f5b7f9f8a22c52b652 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T00:59:50Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-8e717e52ac8e42f5b7f9f8a22c52b6522023-11-18T19:42:05ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-07-0124141159810.3390/ijms241411598NFE2L2 and STAT3 Converge on Common Targets to Promote Survival of Primary Lymphoma CellsAndrea Arena0Michele Di Crosta1Roberta Gonnella2Roberta Zarrella3Maria Anele Romeo4Rossella Benedetti5Maria Saveria Gilardini Montani6Roberta Santarelli7Gabriella D’Orazi8Mara Cirone9Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, ItalyDepartment of Neurosciences, Imaging and Clinical Sciences, University “G. D’Annunzio”, 66013 Chieti, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, ItalyNFE2L2 and STAT3 are key pro-survival molecules, and thus, their targeting may represent a promising anti-cancer strategy. In this study, we found that a positive feedback loop occurred between them and provided evidence that their concomitant inhibition efficiently impaired the survival of PEL cells, a rare, aggressive B cell lymphoma associated with the gammaherpesvirus KSHV and often also EBV. At the molecular level, we found that NFE2L2 and STAT3 converged in the regulation of several pro-survival molecules and in the activation of processes essential for the adaption of lymphoma cells to stress. Among those, STAT3 and NFE2L2 promoted the activation of pathways such as MAPK3/1 and MTOR that positively regulate protein synthesis, sustained the antioxidant response, expression of molecules such as MYC, BIRC5, CCND1, and HSP, and allowed DDR execution. The findings of this study suggest that the concomitant inhibition of NFE2L2 and STAT3 may be considered a therapeutic option for the treatment of this lymphoma that poorly responds to chemotherapies.https://www.mdpi.com/1422-0067/24/14/11598PELSTAT3NRF2HSPsDDRp62/SQSTM1 |
| spellingShingle | Andrea Arena Michele Di Crosta Roberta Gonnella Roberta Zarrella Maria Anele Romeo Rossella Benedetti Maria Saveria Gilardini Montani Roberta Santarelli Gabriella D’Orazi Mara Cirone NFE2L2 and STAT3 Converge on Common Targets to Promote Survival of Primary Lymphoma Cells International Journal of Molecular Sciences PEL STAT3 NRF2 HSPs DDR p62/SQSTM1 |
| title | NFE2L2 and STAT3 Converge on Common Targets to Promote Survival of Primary Lymphoma Cells |
| title_full | NFE2L2 and STAT3 Converge on Common Targets to Promote Survival of Primary Lymphoma Cells |
| title_fullStr | NFE2L2 and STAT3 Converge on Common Targets to Promote Survival of Primary Lymphoma Cells |
| title_full_unstemmed | NFE2L2 and STAT3 Converge on Common Targets to Promote Survival of Primary Lymphoma Cells |
| title_short | NFE2L2 and STAT3 Converge on Common Targets to Promote Survival of Primary Lymphoma Cells |
| title_sort | nfe2l2 and stat3 converge on common targets to promote survival of primary lymphoma cells |
| topic | PEL STAT3 NRF2 HSPs DDR p62/SQSTM1 |
| url | https://www.mdpi.com/1422-0067/24/14/11598 |
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