Academic Journal
Inducing cancer indolence by targeting mitochondrial Complex I is potentiated by blocking macrophage-mediated adaptive responses
| العنوان: | Inducing cancer indolence by targeting mitochondrial Complex I is potentiated by blocking macrophage-mediated adaptive responses |
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| المؤلفون: | Kurelac I., Iommarini L., Vatrinet R., Amato L. B., De Luise M., Leone G., Girolimetti G., Umesh Ganesh N., Bridgeman V. L., Ombrato L., Columbaro M., Ragazzi M., Gibellini L., Sollazzo M., Feichtinger R. G., Vidali S., Baldassarre M., Foriel S., Vidone M., Cossarizza A., Grifoni D., Kofler B., Malanchi I., Porcelli A. M., Gasparre G. |
| المساهمون: | Kurelac, I., Iommarini, L., Vatrinet, R., Amato, L. B., De Luise, M., Leone, G., Girolimetti, G., Umesh Ganesh, N., Bridgeman, V. L., Ombrato, L., Columbaro, M., Ragazzi, M., Gibellini, L., Sollazzo, M., Feichtinger, R. G., Vidali, S., Baldassarre, M., Foriel, S., Vidone, M., Cossarizza, A., Grifoni, D., Kofler, B., Malanchi, I., Porcelli, A. M., Gasparre, G. |
| سنة النشر: | 2019 |
| المجموعة: | Archivio della ricerca dell'Università di Modena e Reggio Emilia (Unimore: IRIS) |
| مصطلحات موضوعية: | Adenoma, Oxyphilic, Aminopyridine, Animal, Antineoplastic Agent, Cell Line, Tumor, Cell Proliferation, Drosophila, Electron Transport Complex I, Female, Gene Knockout Technique, HCT116 Cell, Human, Hypoxia-Inducible Factor 1, alpha Subunit, Macrophage, Metformin, Mice, Knockout, Nude, NADH Dehydrogenase, Neovascularization, Pathologic, Pyrrole, Xenograft Model Antitumor Assays |
| الوصف: | Converting carcinomas in benign oncocytomas has been suggested as a potential anti-cancer strategy. One of the oncocytoma hallmarks is the lack of respiratory complex I (CI). Here we use genetic ablation of this enzyme to induce indolence in two cancer types, and show this is reversed by allowing the stabilization of Hypoxia Inducible Factor-1 alpha (HIF-1α). We further show that on the long run CI-deficient tumors re-adapt to their inability to respond to hypoxia, concordantly with the persistence of human oncocytomas. We demonstrate that CI-deficient tumors survive and carry out angiogenesis, despite their inability to stabilize HIF-1α. Such adaptive response is mediated by tumor associated macrophages, whose blockage improves the effect of CI ablation. Additionally, the simultaneous pharmacological inhibition of CI function through metformin and macrophage infiltration through PLX-3397 impairs tumor growth in vivo in a synergistic manner, setting the basis for an efficient combinatorial adjuvant therapy in clinical trials. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/30796225; info:eu-repo/semantics/altIdentifier/wos/WOS:000459403800008; volume:10; issue:1; firstpage:903; lastpage:N/A; journal:NATURE COMMUNICATIONS; http://hdl.handle.net/11380/1203182; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85062038816 |
| DOI: | 10.1038/s41467-019-08839-1 |
| الاتاحة: | http://hdl.handle.net/11380/1203182 https://doi.org/10.1038/s41467-019-08839-1 |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.E9576CEE |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-019-08839-1 |
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