RIPK1-dependent necroptosis promotes vasculogenic mimicry formation via eIF4E in triple-negative breast cancer
Abstract Necroptosis is a caspase-independent form of programmed cell death. Receptor interacting protein kinase 1 (RIPK1) is a key molecule in the initiation of necroptosis and the formation of the necrotic complex. Vasculogenic mimicry (VM) provides a blood supply to tumor cells that is not depend...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2023-05-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-023-05841-w |
| _version_ | 1797682594593112064 |
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| author | Fan Li Huizhi Sun Yihui Yu Na Che Jiyuan Han Runfen Cheng Nan Zhao Yuhong Guo Chongbiao Huang Danfang Zhang |
| author_facet | Fan Li Huizhi Sun Yihui Yu Na Che Jiyuan Han Runfen Cheng Nan Zhao Yuhong Guo Chongbiao Huang Danfang Zhang |
| author_sort | Fan Li |
| collection | DOAJ |
| description | Abstract Necroptosis is a caspase-independent form of programmed cell death. Receptor interacting protein kinase 1 (RIPK1) is a key molecule in the initiation of necroptosis and the formation of the necrotic complex. Vasculogenic mimicry (VM) provides a blood supply to tumor cells that is not dependent on endothelial cells. However, the relationship between necroptosis and VM in triple-negative breast cancer (TNBC) is not fully understood. In this study, we found that RIPK1-dependent necroptosis promoted VM formation in TNBC. Knockdown of RIPK1 significantly suppressed the number of necroptotic cells and VM formation. Moreover, RIPK1 activated the p-AKT/eIF4E signaling pathway during necroptosis in TNBC. eIF4E was blocked by knockdown of RIPK1 or AKT inhibitors. Furthermore, we found that eIF4E promoted VM formation by promoting epithelial-mesenchymal transition (EMT) and the expression and activity of MMP2. In addition to its critical role in necroptosis-mediated VM, eIF4E was essential for VM formation. Knockdown of eIF4E significantly suppressed VM formation during necroptosis. Finally, through clinical significance, the results found that eIF4E expression in TNBC was positively correlated with the mesenchymal marker vimentin, the VM marker MMP2, and the necroptosis markers MLKL and AKT. In conclusion, RIPK1-dependent necroptosis promotes VM formation in TNBC. Necroptosis promotes VM formation by activating RIPK1/p-AKT/eIF4E signaling in TNBC. eIF4E promotes EMT and MMP2 expression and activity, leading to VM formation. Our study provides a rationale for necroptosis-mediated VM and also providing a potential therapeutic target for TNBC. |
| first_indexed | 2024-03-12T00:02:03Z |
| format | Article |
| id | doaj.art-4c138186728e46aaa3778fa2d12287de |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-03-12T00:02:03Z |
| publishDate | 2023-05-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-4c138186728e46aaa3778fa2d12287de2023-09-17T11:29:19ZengNature Publishing GroupCell Death and Disease2041-48892023-05-0114511610.1038/s41419-023-05841-wRIPK1-dependent necroptosis promotes vasculogenic mimicry formation via eIF4E in triple-negative breast cancerFan Li0Huizhi Sun1Yihui Yu2Na Che3Jiyuan Han4Runfen Cheng5Nan Zhao6Yuhong Guo7Chongbiao Huang8Danfang Zhang9Department of Pathology, Tianjin Medical UniversityTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for CancerDepartment of Pathology, Tianjin Medical UniversityDepartment of Pathology, Tianjin Medical UniversityDepartment of Pathology, Tianjin Medical UniversityTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for CancerDepartment of Pathology, Tianjin Medical UniversityTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for CancerTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for CancerDepartment of Pathology, Tianjin Medical UniversityAbstract Necroptosis is a caspase-independent form of programmed cell death. Receptor interacting protein kinase 1 (RIPK1) is a key molecule in the initiation of necroptosis and the formation of the necrotic complex. Vasculogenic mimicry (VM) provides a blood supply to tumor cells that is not dependent on endothelial cells. However, the relationship between necroptosis and VM in triple-negative breast cancer (TNBC) is not fully understood. In this study, we found that RIPK1-dependent necroptosis promoted VM formation in TNBC. Knockdown of RIPK1 significantly suppressed the number of necroptotic cells and VM formation. Moreover, RIPK1 activated the p-AKT/eIF4E signaling pathway during necroptosis in TNBC. eIF4E was blocked by knockdown of RIPK1 or AKT inhibitors. Furthermore, we found that eIF4E promoted VM formation by promoting epithelial-mesenchymal transition (EMT) and the expression and activity of MMP2. In addition to its critical role in necroptosis-mediated VM, eIF4E was essential for VM formation. Knockdown of eIF4E significantly suppressed VM formation during necroptosis. Finally, through clinical significance, the results found that eIF4E expression in TNBC was positively correlated with the mesenchymal marker vimentin, the VM marker MMP2, and the necroptosis markers MLKL and AKT. In conclusion, RIPK1-dependent necroptosis promotes VM formation in TNBC. Necroptosis promotes VM formation by activating RIPK1/p-AKT/eIF4E signaling in TNBC. eIF4E promotes EMT and MMP2 expression and activity, leading to VM formation. Our study provides a rationale for necroptosis-mediated VM and also providing a potential therapeutic target for TNBC.https://doi.org/10.1038/s41419-023-05841-w |
| spellingShingle | Fan Li Huizhi Sun Yihui Yu Na Che Jiyuan Han Runfen Cheng Nan Zhao Yuhong Guo Chongbiao Huang Danfang Zhang RIPK1-dependent necroptosis promotes vasculogenic mimicry formation via eIF4E in triple-negative breast cancer Cell Death and Disease |
| title | RIPK1-dependent necroptosis promotes vasculogenic mimicry formation via eIF4E in triple-negative breast cancer |
| title_full | RIPK1-dependent necroptosis promotes vasculogenic mimicry formation via eIF4E in triple-negative breast cancer |
| title_fullStr | RIPK1-dependent necroptosis promotes vasculogenic mimicry formation via eIF4E in triple-negative breast cancer |
| title_full_unstemmed | RIPK1-dependent necroptosis promotes vasculogenic mimicry formation via eIF4E in triple-negative breast cancer |
| title_short | RIPK1-dependent necroptosis promotes vasculogenic mimicry formation via eIF4E in triple-negative breast cancer |
| title_sort | ripk1 dependent necroptosis promotes vasculogenic mimicry formation via eif4e in triple negative breast cancer |
| url | https://doi.org/10.1038/s41419-023-05841-w |
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