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http://hdl.handle.net/10261/222247
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Campo DC | Valor | Lengua/Idioma |
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dc.contributor.author | Alcalá, Sonia | es_ES |
dc.contributor.author | Sancho, Patricia | es_ES |
dc.contributor.author | Martinelli, Paola | es_ES |
dc.contributor.author | Navarro, Diego | es_ES |
dc.contributor.author | Pedrero García, Coral | es_ES |
dc.contributor.author | Martin-Hijano, Laura | es_ES |
dc.contributor.author | Valle, Sandra | es_ES |
dc.contributor.author | Earl, Julie | es_ES |
dc.contributor.author | Rodríguez-Serrano, Macarena | es_ES |
dc.contributor.author | Ruiz-Cañas, Laura | es_ES |
dc.contributor.author | Rojas, Katerin | es_ES |
dc.contributor.author | Carrato, Alfredo | es_ES |
dc.contributor.author | García-Bermejo, María Laura | es_ES |
dc.contributor.author | Fernández-Moreno, Miguel Ángel | es_ES |
dc.contributor.author | Hermann, Patrick C. | es_ES |
dc.contributor.author | Sainz, Bruno Jr. | es_ES |
dc.date.accessioned | 2020-11-04T11:14:19Z | - |
dc.date.available | 2020-11-04T11:14:19Z | - |
dc.date.issued | 2020 | - |
dc.identifier.citation | Nature Communications 11: 2682 (2020) | es_ES |
dc.identifier.uri | http://hdl.handle.net/10261/222247 | - |
dc.description.abstract | Pancreatic cancer stem cells (PaCSCs) drive pancreatic cancer tumorigenesis, chemoresistance and metastasis. While eliminating this subpopulation of cells would theoretically result in tumor eradication, PaCSCs are extremely plastic and can successfully adapt to targeted therapies. In this study, we demonstrate that PaCSCs increase expression of interferon-stimulated gene 15 (ISG15) and protein ISGylation, which are essential for maintaining their metabolic plasticity. CRISPR-mediated ISG15 genomic editing reduces overall ISGylation, impairing PaCSCs self-renewal and their in vivo tumorigenic capacity. At the molecular level, ISG15 loss results in decreased mitochondrial ISGylation concomitant with increased accumulation of dysfunctional mitochondria, reduced oxidative phosphorylation (OXPHOS) and impaired mitophagy. Importantly, disruption in mitochondrial metabolism affects PaCSC metabolic plasticity, making them susceptible to prolonged inhibition with metformin in vivo. Thus, ISGylation is critical for optimal and efficient OXPHOS by ensuring the recycling of dysfunctional mitochondria, and when absent, a dysregulation in mitophagy occurs that negatively impacts PaCSC stemness. | es_ES |
dc.description.sponsorship | This study was supported by a Ramón y Cajal Merit Award (RYC-2012-12104) from the Ministerio de Economía y Competitividad, Spain (B.S.); a Conquer Cancer Now Grant from the Concern Foundation (Los Angeles, CA, USA) (B.S.); a Coordinated grant from the Fundación Asociación Española Contra el Cáncer (AECC, GC16173694BARB) (A.C. and B.S.); funding from The Fero Foundation (B.S.); Fondo de Investigaciones Sanitarias (FIS) grants PI15/01507 and PI18/00757 (B.S.), PI15/01715 and PI18/00267 (M.L.G-B.), PI17/00082 (P.S.) and PI15/02101 (A.C.) (all co-financed through Fondo Europeo de Desarrollo Regional (FEDER) “Una manera de hacer Europa”) and a Miguel Servet award (CP16/00121) (P.S.), all from the Instituto de Salud Carlos III (ISCIII), Spain; funding from the Biomedical Research Network in Cancer (CIBERONC:CB16/12/00446) for clinical sample and data collection (A.C.); a Max Eder Fellowship of the German Cancer Aid (111746) (P.C.H.); the German Research Foundation (DFG, CRC 1279 “Exploiting the human peptidome for Novel Antimicrobial and Anticancer Agents”) (P.C.H.); and the Austrian Science Fund (FWF-B27361) and Ingrid Shaker-Nessmann Foundation for Cancer Research (P.M.). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Springer Nature | es_ES |
dc.relation.isversionof | Publisher's version | es_ES |
dc.rights | openAccess | es_ES |
dc.title | ISG15 and ISGylation is required for pancreatic cancer stem cell mitophagy and metabolic plasticity | es_ES |
dc.type | artículo | es_ES |
dc.identifier.doi | 10.1038/s41467-020-16395-2 | - |
dc.description.peerreviewed | Peer reviewed | es_ES |
dc.relation.publisherversion | https://doi.org/10.1038/s41467-020-16395-2 | es_ES |
dc.identifier.e-issn | 2041-1723 | - |
dc.rights.license | http://creativecommons.org/licenses/by/4.0/ | es_ES |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | es_ES |
dc.contributor.funder | Concern Foundation | es_ES |
dc.contributor.funder | Fundación Científica Asociación Española Contra el Cáncer | es_ES |
dc.contributor.funder | Fundación Fero | es_ES |
dc.contributor.funder | Instituto de Salud Carlos III | es_ES |
dc.contributor.funder | European Commission | es_ES |
dc.contributor.funder | German Cancer Aid | es_ES |
dc.contributor.funder | German Research Foundation | es_ES |
dc.contributor.funder | Austrian Science Fund | es_ES |
dc.contributor.funder | European Commission | es_ES |
dc.relation.csic | Sí | es_ES |
oprm.item.hasRevision | no ko 0 false | * |
dc.identifier.funder | http://dx.doi.org/10.13039/501100004587 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100002428 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/100001558 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100000780 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100002704 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100001659 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100003329 | es_ES |
dc.identifier.pmid | 32472071 | - |
dc.type.coar | http://purl.org/coar/resource_type/c_6501 | es_ES |
item.cerifentitytype | Publications | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.grantfulltext | open | - |
item.openairetype | artículo | - |
item.fulltext | With Fulltext | - |
item.languageiso639-1 | en | - |
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isgplasti.pdf | 5,81 MB | Adobe PDF | Visualizar/Abrir |
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