p53 Suppresses Metabolic Stress-Induced Ferroptosis in Cancer Cells
How cancer cells respond to nutrient deprivation remains poorly understood. In certain cancer cells, deprivation of cystine induces a non-apoptotic, iron-dependent form of cell death termed ferroptosis. Recent evidence suggests that ferroptosis sensitivity may be modulated by the stress-responsive t...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-01-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717319149 |
| _version_ | 1819170482048466944 |
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| author | Amy Tarangelo Leslie Magtanong Kathryn T. Bieging-Rolett Yang Li Jiangbin Ye Laura D. Attardi Scott J. Dixon |
| author_facet | Amy Tarangelo Leslie Magtanong Kathryn T. Bieging-Rolett Yang Li Jiangbin Ye Laura D. Attardi Scott J. Dixon |
| author_sort | Amy Tarangelo |
| collection | DOAJ |
| description | How cancer cells respond to nutrient deprivation remains poorly understood. In certain cancer cells, deprivation of cystine induces a non-apoptotic, iron-dependent form of cell death termed ferroptosis. Recent evidence suggests that ferroptosis sensitivity may be modulated by the stress-responsive transcription factor and canonical tumor suppressor protein p53. Using CRISPR/Cas9 genome editing, small-molecule probes, and high-resolution, time-lapse imaging, we find that stabilization of wild-type p53 delays the onset of ferroptosis in response to cystine deprivation. This delay requires the p53 transcriptional target CDKN1A (encoding p21) and is associated with both slower depletion of intracellular glutathione and a reduced accumulation of toxic lipid-reactive oxygen species (ROS). Thus, the p53-p21 axis may help cancer cells cope with metabolic stress induced by cystine deprivation by delaying the onset of non-apoptotic cell death. |
| first_indexed | 2024-12-22T19:36:05Z |
| format | Article |
| id | doaj.art-65fa87ec72d24c9a89ee70935269d022 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-22T19:36:05Z |
| publishDate | 2018-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-65fa87ec72d24c9a89ee70935269d0222022-12-21T18:14:57ZengElsevierCell Reports2211-12472018-01-0122356957510.1016/j.celrep.2017.12.077p53 Suppresses Metabolic Stress-Induced Ferroptosis in Cancer CellsAmy Tarangelo0Leslie Magtanong1Kathryn T. Bieging-Rolett2Yang Li3Jiangbin Ye4Laura D. Attardi5Scott J. Dixon6Program in Cancer Biology, Stanford University School of Medicine, 291 Campus Drive, Stanford, CA 94305, USADepartment of Biology, Stanford University, 337 Campus Drive, Stanford, CA 94305, USADepartment of Radiation Oncology, Stanford University School of Medicine, 291 Campus Drive, Stanford, CA 94305, USAProgram in Cancer Biology, Stanford University School of Medicine, 291 Campus Drive, Stanford, CA 94305, USAProgram in Cancer Biology, Stanford University School of Medicine, 291 Campus Drive, Stanford, CA 94305, USAProgram in Cancer Biology, Stanford University School of Medicine, 291 Campus Drive, Stanford, CA 94305, USAProgram in Cancer Biology, Stanford University School of Medicine, 291 Campus Drive, Stanford, CA 94305, USAHow cancer cells respond to nutrient deprivation remains poorly understood. In certain cancer cells, deprivation of cystine induces a non-apoptotic, iron-dependent form of cell death termed ferroptosis. Recent evidence suggests that ferroptosis sensitivity may be modulated by the stress-responsive transcription factor and canonical tumor suppressor protein p53. Using CRISPR/Cas9 genome editing, small-molecule probes, and high-resolution, time-lapse imaging, we find that stabilization of wild-type p53 delays the onset of ferroptosis in response to cystine deprivation. This delay requires the p53 transcriptional target CDKN1A (encoding p21) and is associated with both slower depletion of intracellular glutathione and a reduced accumulation of toxic lipid-reactive oxygen species (ROS). Thus, the p53-p21 axis may help cancer cells cope with metabolic stress induced by cystine deprivation by delaying the onset of non-apoptotic cell death.http://www.sciencedirect.com/science/article/pii/S2211124717319149p53cell deathmetabolismcancerferroptosisreactive oxygen speciesglutathionecystine |
| spellingShingle | Amy Tarangelo Leslie Magtanong Kathryn T. Bieging-Rolett Yang Li Jiangbin Ye Laura D. Attardi Scott J. Dixon p53 Suppresses Metabolic Stress-Induced Ferroptosis in Cancer Cells Cell Reports p53 cell death metabolism cancer ferroptosis reactive oxygen species glutathione cystine |
| title | p53 Suppresses Metabolic Stress-Induced Ferroptosis in Cancer Cells |
| title_full | p53 Suppresses Metabolic Stress-Induced Ferroptosis in Cancer Cells |
| title_fullStr | p53 Suppresses Metabolic Stress-Induced Ferroptosis in Cancer Cells |
| title_full_unstemmed | p53 Suppresses Metabolic Stress-Induced Ferroptosis in Cancer Cells |
| title_short | p53 Suppresses Metabolic Stress-Induced Ferroptosis in Cancer Cells |
| title_sort | p53 suppresses metabolic stress induced ferroptosis in cancer cells |
| topic | p53 cell death metabolism cancer ferroptosis reactive oxygen species glutathione cystine |
| url | http://www.sciencedirect.com/science/article/pii/S2211124717319149 |
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