Suppression of the SLC7A11/glutathione axis causes ferroptosis and apoptosis and alters the mitogen-activated protein kinase pathway in nasopharyngeal carcinoma
Copyright © 2023. Published by Elsevier B.V..
SLC7A11 is a unit of the glutamate cystine antiporter Xc- system. It functions to import cystine for glutathione biosynthesis and maintains the redox balance in cells. Sorafenib inhibits the transporter activity of SLC7A11. The use of sorafenib has been approved in the treatment of multiple cancers. However, at present, our understanding of the mechanism of SLC7A11 and sorafenib in nasopharyngeal carcinoma (NPC) remains limited. We found that the expression of SLC7A11 was upregulated in NPC. A high SLC7A11 expression was associated with poor prognosis, metastasis, and an advanced T stage, which can be used as an independent prognostic indicator of NPC. In vitro, we observed that NPC cells relied on cystine for survival. Targeting SLC7A11 resulted in glutathione biosynthesis limitation, intracellular reactive oxygen species accumulation, lipid peroxides, ferroptosis, and apoptosis. Meanwhile, it altered mitogen activated protein kinase pathway, including p38 activation but ERK inhibition in NPC. This limited the proliferation of NPC cells. Sorafenib inhibited the proliferation and induced the death of NPC cells in vivo. In conclusion, SLC7A11 plays an important role in the occurrence and progression of NPC and may be a novel target for NPC treatment.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:254 |
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| Enthalten in: |
International journal of biological macromolecules - 254(2024), Pt 3 vom: 15. Jan., Seite 127976 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Hai-Hua [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 05.01.2024 Date Revised 06.01.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ijbiomac.2023.127976 |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Suppression of the SLC7A11/glutathione axis causes ferroptosis and apoptosis and alters the mitogen-activated protein kinase pathway in nasopharyngeal carcinoma |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023. Published by Elsevier B.V. | ||
| 520 | |a SLC7A11 is a unit of the glutamate cystine antiporter Xc- system. It functions to import cystine for glutathione biosynthesis and maintains the redox balance in cells. Sorafenib inhibits the transporter activity of SLC7A11. The use of sorafenib has been approved in the treatment of multiple cancers. However, at present, our understanding of the mechanism of SLC7A11 and sorafenib in nasopharyngeal carcinoma (NPC) remains limited. We found that the expression of SLC7A11 was upregulated in NPC. A high SLC7A11 expression was associated with poor prognosis, metastasis, and an advanced T stage, which can be used as an independent prognostic indicator of NPC. In vitro, we observed that NPC cells relied on cystine for survival. Targeting SLC7A11 resulted in glutathione biosynthesis limitation, intracellular reactive oxygen species accumulation, lipid peroxides, ferroptosis, and apoptosis. Meanwhile, it altered mitogen activated protein kinase pathway, including p38 activation but ERK inhibition in NPC. This limited the proliferation of NPC cells. Sorafenib inhibited the proliferation and induced the death of NPC cells in vivo. In conclusion, SLC7A11 plays an important role in the occurrence and progression of NPC and may be a novel target for NPC treatment | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Apoptosis | |
| 650 | 4 | |a Ferroptosis | |
| 650 | 4 | |a Glutathione | |
| 650 | 4 | |a Nasopharyngeal carcinoma | |
| 650 | 4 | |a SLC7A11 | |
| 650 | 4 | |a Sorafenib | |
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| 700 | 1 | |a Fan, Song-Qing |e verfasserin |4 aut | |
| 700 | 1 | |a Zhan, Yu-Ting |e verfasserin |4 aut | |
| 700 | 1 | |a Peng, Shu-Ping |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Wei-Yuan |e verfasserin |4 aut | |
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