Oncogenic RTKs sensitize cancer cells to ferroptosis via c-Myc mediated upregulation of ACSL4
Abstract Alteration or abnormal activation of RTKs have been recurrently observed and recognized as an important driving factor in the progression of many human cancers. Ferroptosis, an iron-dependent form of regulated necrosis triggered by the accumulation of lethal lipid peroxides on cell membrane...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2024-11-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-024-07254-9 |
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| _version_ | 1846147332882563072 |
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| author | Na Sun Jiawa Wang Jianhua Qin Shuang Ma Jing Luan Guoyuan Hou Wei Zhang Minghui Gao |
| author_facet | Na Sun Jiawa Wang Jianhua Qin Shuang Ma Jing Luan Guoyuan Hou Wei Zhang Minghui Gao |
| author_sort | Na Sun |
| collection | DOAJ |
| description | Abstract Alteration or abnormal activation of RTKs have been recurrently observed and recognized as an important driving factor in the progression of many human cancers. Ferroptosis, an iron-dependent form of regulated necrosis triggered by the accumulation of lethal lipid peroxides on cell membranes, has been implicated in various tumor types. Here we reported that oncogenic RTKs/RAS/RAF/c-Myc axis promotes cancer cells to ferroptosis. Mechanistically, c-Myc binds to the promoter region of ACSL4 and promotes the expression of ACSL4, thereby sensitizes cells to ferroptosis. We further showed that RTKs/RAS/RAF promote ferroptosis by upregulating c-Myc mediated expression of ACSL4 in cancer cells. Notably, overexpression of RTKs enhances the vulnerability of melanoma to the ferroptosis inducer in mouse xenograft model. These findings may provide an attractive intervention strategy to target cancers with oncogenic activation of RTKs via a ferroptosis-inducing approach. |
| format | Article |
| id | doaj-art-1313b8a1752c44a1a83a8378750a7ece |
| institution | Kabale University |
| issn | 2041-4889 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj-art-1313b8a1752c44a1a83a8378750a7ece2024-12-01T12:47:31ZengNature Publishing GroupCell Death and Disease2041-48892024-11-01151111110.1038/s41419-024-07254-9Oncogenic RTKs sensitize cancer cells to ferroptosis via c-Myc mediated upregulation of ACSL4Na Sun0Jiawa Wang1Jianhua Qin2Shuang Ma3Jing Luan4Guoyuan Hou5Wei Zhang6Minghui Gao7The HIT Center for Life Sciences, School of Life Science and Technology, Harbin Institute of TechnologyThe HIT Center for Life Sciences, School of Life Science and Technology, Harbin Institute of TechnologyThe HIT Center for Life Sciences, School of Life Science and Technology, Harbin Institute of TechnologyThe HIT Center for Life Sciences, School of Life Science and Technology, Harbin Institute of TechnologyThe HIT Center for Life Sciences, School of Life Science and Technology, Harbin Institute of TechnologyThe HIT Center for Life Sciences, School of Life Science and Technology, Harbin Institute of TechnologyDepartment of Microbiology and Immunology, Weill Cornell MedicineThe HIT Center for Life Sciences, School of Life Science and Technology, Harbin Institute of TechnologyAbstract Alteration or abnormal activation of RTKs have been recurrently observed and recognized as an important driving factor in the progression of many human cancers. Ferroptosis, an iron-dependent form of regulated necrosis triggered by the accumulation of lethal lipid peroxides on cell membranes, has been implicated in various tumor types. Here we reported that oncogenic RTKs/RAS/RAF/c-Myc axis promotes cancer cells to ferroptosis. Mechanistically, c-Myc binds to the promoter region of ACSL4 and promotes the expression of ACSL4, thereby sensitizes cells to ferroptosis. We further showed that RTKs/RAS/RAF promote ferroptosis by upregulating c-Myc mediated expression of ACSL4 in cancer cells. Notably, overexpression of RTKs enhances the vulnerability of melanoma to the ferroptosis inducer in mouse xenograft model. These findings may provide an attractive intervention strategy to target cancers with oncogenic activation of RTKs via a ferroptosis-inducing approach.https://doi.org/10.1038/s41419-024-07254-9 |
| spellingShingle | Na Sun Jiawa Wang Jianhua Qin Shuang Ma Jing Luan Guoyuan Hou Wei Zhang Minghui Gao Oncogenic RTKs sensitize cancer cells to ferroptosis via c-Myc mediated upregulation of ACSL4 Cell Death and Disease |
| title | Oncogenic RTKs sensitize cancer cells to ferroptosis via c-Myc mediated upregulation of ACSL4 |
| title_full | Oncogenic RTKs sensitize cancer cells to ferroptosis via c-Myc mediated upregulation of ACSL4 |
| title_fullStr | Oncogenic RTKs sensitize cancer cells to ferroptosis via c-Myc mediated upregulation of ACSL4 |
| title_full_unstemmed | Oncogenic RTKs sensitize cancer cells to ferroptosis via c-Myc mediated upregulation of ACSL4 |
| title_short | Oncogenic RTKs sensitize cancer cells to ferroptosis via c-Myc mediated upregulation of ACSL4 |
| title_sort | oncogenic rtks sensitize cancer cells to ferroptosis via c myc mediated upregulation of acsl4 |
| url | https://doi.org/10.1038/s41419-024-07254-9 |
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