dc.contributor.author | Kurelac, I | |
dc.contributor.author | Iommarinio, L | |
dc.contributor.author | Vatrinet, R | |
dc.contributor.author | Amato, LB | |
dc.contributor.author | De Luise, M | |
dc.contributor.author | Leone, G | |
dc.contributor.author | Girolimetti, G | |
dc.contributor.author | Ganesh, NU | |
dc.contributor.author | Bridgeman, VL | |
dc.contributor.author | Ombrato, L | |
dc.contributor.author | Columbaro, M | |
dc.contributor.author | Ragazzi, M | |
dc.contributor.author | Gibellini, L | |
dc.contributor.author | Sollazzo, M | |
dc.contributor.author | Feichtinger, RG | |
dc.contributor.author | Vidali, S | |
dc.contributor.author | Baldassarre, M | |
dc.contributor.author | Foriel, S | |
dc.contributor.author | Vidone, M | |
dc.contributor.author | Cossarizza, A | |
dc.contributor.author | Grifoni, D | |
dc.contributor.author | Kofler, B | |
dc.contributor.author | Malanchi, I | |
dc.contributor.author | Porcelli, AM | |
dc.contributor.author | Gasparre, G | |
dc.date.accessioned | 2020-12-16T10:12:34Z | |
dc.date.available | 2019-01-30 | |
dc.date.available | 2020-12-16T10:12:34Z | |
dc.date.issued | 2019-02-22 | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.other | ARTN 903 | |
dc.identifier.other | ARTN 903 | |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/69323 | |
dc.description.abstract | Converting carcinomas in benign oncocytomas has been suggested as a potential anti-cancerstrategy. One of the oncocytoma hallmarks is the lack of respiratory complex I (CI). Herewe use genetic ablation of this enzyme to induce indolence in two cancer types, andshow 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 inabilityto respond to hypoxia, concordantly with the persistence of human oncocytomas. Wedemonstrate that CI-deficient tumors survive and carry out angiogenesis, despite theirinability to stabilize HIF-1α. Such adaptive response is mediated by tumor associated mac-rophages, whose blockage improves the effect of CI ablation. Additionally, the simultaneouspharmacological inhibition of CI function through metformin and macrophage infiltrationthrough PLX-3397 impairs tumor growth in vivo in a synergistic manner, setting the basisfor an efficient combinatorial adjuvant therapy in clinical trials. | en_US |
dc.relation.ispartof | NATURE COMMUNICATIONS | |
dc.rights | Creative Commons Attribution 4.0 International License | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.title | Inducing cancer indolence by targeting mitochondrial Complex I is potentiated by blocking macrophage-mediated adaptive responses | en_US |
dc.type | Article | en_US |
dc.rights.holder | © The Author(s) 2019 | |
dc.identifier.doi | 10.1038/s41467-019-08839-1 | |
pubs.author-url | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000459403800008&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=612ae0d773dcbdba3046f6df545e9f6a | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published | en_US |
pubs.volume | 10 | en_US |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |