Exploiting Integrin-αVβ3 to Enhance Radiotherapy Efficacy in Medulloblastoma via Ferroptosis
Medulloblastoma, a malignant pediatric brain tumor, has a poor prognosis upon relapse, highlighting a critical clinical need. Our previous research linked medulloblastoma cell radioresistance to integrin-αvβ3 expression. β3-depleted (β3_KO) medulloblastoma cells exhibit lipid hydroxyperoxide accumul...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-11-01
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| Series: | Current Oncology |
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| Online Access: | https://www.mdpi.com/1718-7729/31/11/545 |
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| author | Célia Gotorbe Fabien Segui William Echavidre Jérôme Durivault Thays Blanchard Valérie Vial Marina Pagnuzzi-Boncompagni Rémy Villeneuve Régis Amblard Nicolas Garnier Cécile Ortholan Benjamin Serrano Vincent Picco Jacques Pouysségur Milica Vucetic Christopher Montemagno |
| author_facet | Célia Gotorbe Fabien Segui William Echavidre Jérôme Durivault Thays Blanchard Valérie Vial Marina Pagnuzzi-Boncompagni Rémy Villeneuve Régis Amblard Nicolas Garnier Cécile Ortholan Benjamin Serrano Vincent Picco Jacques Pouysségur Milica Vucetic Christopher Montemagno |
| author_sort | Célia Gotorbe |
| collection | DOAJ |
| description | Medulloblastoma, a malignant pediatric brain tumor, has a poor prognosis upon relapse, highlighting a critical clinical need. Our previous research linked medulloblastoma cell radioresistance to integrin-αvβ3 expression. β3-depleted (β3_KO) medulloblastoma cells exhibit lipid hydroxyperoxide accumulation after radiotherapy, indicating ferroptosis, a regulated cell death induced by ROS and inhibited by antioxidants such as cysteine, glutathione (GSH), and glutathione peroxidase 4 (GPx4). However, the link between αvβ3 expression, ferroptosis inhibition, and sensitivity to radiotherapy remains unclear. We showed that irradiated β3_KO medulloblastoma cells primarily die by ferroptosis, with β3-subunit expression correlating with radiotherapy sensitivity and anti-ferroptotic protein levels. Our findings suggest that integrin-αvβ3 signaling boosts oxidative stress resilience via mTORC1. Thus, targeting integrin-αvβ3 could enhance radiotherapy efficacy in medulloblastoma by inducing ferroptotic cell death. |
| format | Article |
| id | doaj-art-6e6ee2efabe044e8922a5b5df1a8d774 |
| institution | Kabale University |
| issn | 1198-0052 1718-7729 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Current Oncology |
| spelling | doaj-art-6e6ee2efabe044e8922a5b5df1a8d7742024-11-26T17:59:06ZengMDPI AGCurrent Oncology1198-00521718-77292024-11-0131117390740210.3390/curroncol31110545Exploiting Integrin-αVβ3 to Enhance Radiotherapy Efficacy in Medulloblastoma via FerroptosisCélia Gotorbe0Fabien Segui1William Echavidre2Jérôme Durivault3Thays Blanchard4Valérie Vial5Marina Pagnuzzi-Boncompagni6Rémy Villeneuve7Régis Amblard8Nicolas Garnier9Cécile Ortholan10Benjamin Serrano11Vincent Picco12Jacques Pouysségur13Milica Vucetic14Christopher Montemagno15Biomedical Department, Centre Scientifique de Monaco, 98000 Monaco, MonacoBiomedical Department, Centre Scientifique de Monaco, 98000 Monaco, MonacoBiomedical Department, Centre Scientifique de Monaco, 98000 Monaco, MonacoBiomedical Department, Centre Scientifique de Monaco, 98000 Monaco, MonacoBiomedical Department, Centre Scientifique de Monaco, 98000 Monaco, MonacoBiomedical Department, Centre Scientifique de Monaco, 98000 Monaco, MonacoBiomedical Department, Centre Scientifique de Monaco, 98000 Monaco, MonacoRadiophysics Department, Princess Grace Hospital, 98000 Monaco, MonacoRadiophysics Department, Princess Grace Hospital, 98000 Monaco, MonacoRadiophysics Department, Princess Grace Hospital, 98000 Monaco, MonacoRadiotherapy Department, Princess Grace Hospital, 98000 Monaco, MonacoRadiophysics Department, Princess Grace Hospital, 98000 Monaco, MonacoBiomedical Department, Centre Scientifique de Monaco, 98000 Monaco, MonacoBiomedical Department, Centre Scientifique de Monaco, 98000 Monaco, MonacoBiomedical Department, Centre Scientifique de Monaco, 98000 Monaco, MonacoBiomedical Department, Centre Scientifique de Monaco, 98000 Monaco, MonacoMedulloblastoma, a malignant pediatric brain tumor, has a poor prognosis upon relapse, highlighting a critical clinical need. Our previous research linked medulloblastoma cell radioresistance to integrin-αvβ3 expression. β3-depleted (β3_KO) medulloblastoma cells exhibit lipid hydroxyperoxide accumulation after radiotherapy, indicating ferroptosis, a regulated cell death induced by ROS and inhibited by antioxidants such as cysteine, glutathione (GSH), and glutathione peroxidase 4 (GPx4). However, the link between αvβ3 expression, ferroptosis inhibition, and sensitivity to radiotherapy remains unclear. We showed that irradiated β3_KO medulloblastoma cells primarily die by ferroptosis, with β3-subunit expression correlating with radiotherapy sensitivity and anti-ferroptotic protein levels. Our findings suggest that integrin-αvβ3 signaling boosts oxidative stress resilience via mTORC1. Thus, targeting integrin-αvβ3 could enhance radiotherapy efficacy in medulloblastoma by inducing ferroptotic cell death.https://www.mdpi.com/1718-7729/31/11/545integrin-αvβ3medulloblastomacilengitideradiotherapyferroptosis |
| spellingShingle | Célia Gotorbe Fabien Segui William Echavidre Jérôme Durivault Thays Blanchard Valérie Vial Marina Pagnuzzi-Boncompagni Rémy Villeneuve Régis Amblard Nicolas Garnier Cécile Ortholan Benjamin Serrano Vincent Picco Jacques Pouysségur Milica Vucetic Christopher Montemagno Exploiting Integrin-αVβ3 to Enhance Radiotherapy Efficacy in Medulloblastoma via Ferroptosis Current Oncology integrin-αvβ3 medulloblastoma cilengitide radiotherapy ferroptosis |
| title | Exploiting Integrin-αVβ3 to Enhance Radiotherapy Efficacy in Medulloblastoma via Ferroptosis |
| title_full | Exploiting Integrin-αVβ3 to Enhance Radiotherapy Efficacy in Medulloblastoma via Ferroptosis |
| title_fullStr | Exploiting Integrin-αVβ3 to Enhance Radiotherapy Efficacy in Medulloblastoma via Ferroptosis |
| title_full_unstemmed | Exploiting Integrin-αVβ3 to Enhance Radiotherapy Efficacy in Medulloblastoma via Ferroptosis |
| title_short | Exploiting Integrin-αVβ3 to Enhance Radiotherapy Efficacy in Medulloblastoma via Ferroptosis |
| title_sort | exploiting integrin αvβ3 to enhance radiotherapy efficacy in medulloblastoma via ferroptosis |
| topic | integrin-αvβ3 medulloblastoma cilengitide radiotherapy ferroptosis |
| url | https://www.mdpi.com/1718-7729/31/11/545 |
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