Inhibiting system xC− and glutathione biosynthesis – a potential Achilles' heel in mutant-p53 cancers
Effective therapeutic strategies to target mutant tumor protein p53 (TP53, best known as p53) cancers remain an unmet medical need. We found that mutant p53 impairs the function of nuclear factor (erythroid-derived 2)-like 2 (NFE2L2, commonly known as NRF2), suppresses solute carrier family 7 member...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2017-09-01
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| Series: | Molecular & Cellular Oncology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/23723556.2017.1344757 |
| _version_ | 1827809395681001472 |
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| author | Nicholas J. Clemons David S. Liu Cuong P. Duong Wayne A. Phillips |
| author_facet | Nicholas J. Clemons David S. Liu Cuong P. Duong Wayne A. Phillips |
| author_sort | Nicholas J. Clemons |
| collection | DOAJ |
| description | Effective therapeutic strategies to target mutant tumor protein p53 (TP53, best known as p53) cancers remain an unmet medical need. We found that mutant p53 impairs the function of nuclear factor (erythroid-derived 2)-like 2 (NFE2L2, commonly known as NRF2), suppresses solute carrier family 7 member 11 (SLC7A11) expression, and diminishes cellular glutamate/cystine exchange. This decreases glutathione biosynthesis, resulting in redox imbalance. Mutant p53 tumors are thus inherently susceptible to further perturbations of the SLC7A11/glutathione axis. |
| first_indexed | 2024-03-11T22:41:36Z |
| format | Article |
| id | doaj.art-348115661eca484bbf949019178edd01 |
| institution | Directory Open Access Journal |
| issn | 2372-3556 |
| language | English |
| last_indexed | 2024-03-11T22:41:36Z |
| publishDate | 2017-09-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Molecular & Cellular Oncology |
| spelling | doaj.art-348115661eca484bbf949019178edd012023-09-22T09:10:58ZengTaylor & Francis GroupMolecular & Cellular Oncology2372-35562017-09-014510.1080/23723556.2017.13447571344757Inhibiting system xC− and glutathione biosynthesis – a potential Achilles' heel in mutant-p53 cancersNicholas J. Clemons0David S. Liu1Cuong P. Duong2Wayne A. Phillips3Division of Cancer Research, Peter MacCallum Cancer CentreDivision of Cancer Research, Peter MacCallum Cancer CentreDivision of Cancer Surgery, Peter MacCallum Cancer CentreDivision of Cancer Research, Peter MacCallum Cancer CentreEffective therapeutic strategies to target mutant tumor protein p53 (TP53, best known as p53) cancers remain an unmet medical need. We found that mutant p53 impairs the function of nuclear factor (erythroid-derived 2)-like 2 (NFE2L2, commonly known as NRF2), suppresses solute carrier family 7 member 11 (SLC7A11) expression, and diminishes cellular glutamate/cystine exchange. This decreases glutathione biosynthesis, resulting in redox imbalance. Mutant p53 tumors are thus inherently susceptible to further perturbations of the SLC7A11/glutathione axis.http://dx.doi.org/10.1080/23723556.2017.1344757apr-246glutathione (gsh)nfe2l2nrf2p53prima-1metreactive oxygen species (ros)slc7a11system xc−xct |
| spellingShingle | Nicholas J. Clemons David S. Liu Cuong P. Duong Wayne A. Phillips Inhibiting system xC− and glutathione biosynthesis – a potential Achilles' heel in mutant-p53 cancers Molecular & Cellular Oncology apr-246 glutathione (gsh) nfe2l2 nrf2 p53 prima-1met reactive oxygen species (ros) slc7a11 system xc− xct |
| title | Inhibiting system xC− and glutathione biosynthesis – a potential Achilles' heel in mutant-p53 cancers |
| title_full | Inhibiting system xC− and glutathione biosynthesis – a potential Achilles' heel in mutant-p53 cancers |
| title_fullStr | Inhibiting system xC− and glutathione biosynthesis – a potential Achilles' heel in mutant-p53 cancers |
| title_full_unstemmed | Inhibiting system xC− and glutathione biosynthesis – a potential Achilles' heel in mutant-p53 cancers |
| title_short | Inhibiting system xC− and glutathione biosynthesis – a potential Achilles' heel in mutant-p53 cancers |
| title_sort | inhibiting system xc and glutathione biosynthesis a potential achilles heel in mutant p53 cancers |
| topic | apr-246 glutathione (gsh) nfe2l2 nrf2 p53 prima-1met reactive oxygen species (ros) slc7a11 system xc− xct |
| url | http://dx.doi.org/10.1080/23723556.2017.1344757 |
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