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 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.
Authors
- Marina Pagnuzzi‐Boncompagni
- Jérôme Durivault (ORCID: https://orcid.org/0000-0002-8228-2915)
- Thays Blanchard (ORCID: https://orcid.org/0009-0006-6030-9079)
- Célia Gotorbe (ORCID: https://orcid.org/0009-0000-6883-6187)
- Cécile Ortholan (ORCID: https://orcid.org/0009-0002-3305-5748)
- Vincent Picco (ORCID: https://orcid.org/0000-0001-5251-1521)
- Christopher Montemagno (ORCID: https://orcid.org/0000-0002-5687-1812)
- Benjamín Serrano (ORCID: https://orcid.org/0000-0002-2210-9803)
- Régis Amblard (ORCID: https://orcid.org/0000-0002-9050-3116)
- Nicolas Garnier (ORCID: https://orcid.org/0000-0002-7883-7615)
- William Echavidre (ORCID: https://orcid.org/0009-0008-6042-4522)
- Rémy Villeneuve (ORCID: https://orcid.org/0009-0004-4987-7839)
- Valérie Vial (ORCID: https://orcid.org/0000-0002-8423-4167)
- Jacques Pouysségur (ORCID: https://orcid.org/0000-0003-2779-6902)
- Fabien Segui
- Milica Vučetić (ORCID: https://orcid.org/0000-0002-8542-4296)
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Princess Grace Hospital Centre (MC)
- Institut de Recherche sur le Cancer et le Vieillissement de Nice (FR)
- Scientific Centre of Monaco (MC)
Publication Details
- Journal
- Current Oncology
- Published
- 2024-11-20
- DOI
- https://doi.org/10.3390/curroncol31110545
- Citations
- 3
- Primary Topic
- Ferroptosis and cancer prognosis
- Type
- article
- Field-Weighted Citation Impact
- 1.26
Funders
- Strong