dc.contributor.author | Cash, Timothy P. | |
dc.contributor.author | Alcalá, Sonia | |
dc.contributor.author | Rico-Ferreira, María Del Rosario | |
dc.contributor.author | Hernández-Encinas, Elena | |
dc.contributor.author | García, Jennifer | |
dc.contributor.author | Albarrán, María Isabel | |
dc.contributor.author | Valle, Sandra | |
dc.contributor.author | Muñoz, Javier | |
dc.contributor.author | Martínez-González, Sonia | |
dc.contributor.author | Blanco-Aparicio, Carmen | |
dc.contributor.author | Pastor, Joaquín | |
dc.contributor.author | Serrano, Manuel | |
dc.contributor.author | Sainz, Bruno | |
dc.contributor.other | UAM. Departamento de Bioquímica | es_ES |
dc.contributor.other | Instituto de Investigaciones Biomédicas "Alberto Sols" (IIBM) | es_ES |
dc.date.accessioned | 2021-04-21T15:23:37Z | |
dc.date.available | 2021-04-21T15:23:37Z | |
dc.date.issued | 2020-07-04 | |
dc.identifier.citation | Cancers 12.7 (2020): 1790 | en_US |
dc.identifier.issn | 2072-6694 | es_ES |
dc.identifier.uri | http://hdl.handle.net/10486/694718 | |
dc.description.abstract | Despite significant efforts to improve pancreatic ductal adenocarcinoma (PDAC) clinical outcomes, overall survival remains dismal. The poor response to current therapies is partly due to the existence of pancreatic cancer stem cells (PaCSCs), which are efficient drivers of PDAC tumorigenesis, metastasis and relapse. To find new therapeutic agents that could efficiently kill PaCSCs, we screened a chemical library of 680 compounds for candidate small molecules with anti-CSC activity, and identified two compounds of a specific chemical series with potent activity in vitro and in vivo against patient-derived xenograft (PDX) cultures. The anti-CSC mechanism of action of this specific chemical series was found to rely on induction of lysosomal membrane permeabilization (LMP), which is likely associated with the increased lysosomal mass observed in PaCSCs. Using the well characterized LMP-inducer siramesine as a tool molecule, we show elimination of the PaCSC population in mice implanted with tumors from two PDX models. Collectively, our approach identified lysosomal disruption as a promising anti-CSC therapeutic strategy for PDAC. | en_US |
dc.description.sponsorship | This study was financially supported by a Ramón y Cajal Merit Award (RYC-2012-12104) from the Ministerio de Economía y Competitividad, Spain (B.S.Jr.); funding fromThe Fero Foundation (B.S.Jr.); a Coordinated
grant from the Fundación Asociación Española Contra el Cáncer (AECC) GC16173694BARB (B.S.,Jr.); Fondo de
Investigaciones Sanitarias (FIS) grant PI15/01507 and PI18/00757 (B.S.,Jr.), (cofinanced through Fondo Europeo de
Desarrollo Regional (FEDER) “Una manera de hacer Europa”). ETP activities were supported by funds of The
Spanish National Cancer Research Centre (CNIO).Work in the laboratory of M.S. was funded by the CNIO, the
IRB and “laCaixa” Foundation, and by grants from the Spanish Ministry of Economy co-funded by the European
Regional Development Fund (ERDF) (SAF2017-82613-R), the European Research Council (ERC-2014-AdG/669622)
and, Secretaria d’Universitats i Recerca del Departament d’Empresa i Coneixement of Catalonia (Grup de Recerca consolidat 2017 SGR 282). | en_US |
dc.format.extent | 24 pag. | es_ES |
dc.format.mimetype | application/pdf | en |
dc.language.iso | eng | en_US |
dc.publisher | MDPI, Basel, Switzerland | en_US |
dc.relation.ispartof | Cancers | en_US |
dc.rights | © 2020 The authors. | en_US |
dc.subject.other | Cancer stem cells | en_US |
dc.subject.other | Compound library | en_US |
dc.subject.other | Lysosomal membrane permeabilization | en_US |
dc.subject.other | Pancreatic ductal adenocarcinoma | en_US |
dc.subject.other | Patient-derived xenografts | en_US |
dc.title | Induction of lysosome membrane permeabilization as a therapeutic strategy to target pancreatic cancer stem cells | en_US |
dc.type | article | en |
dc.subject.eciencia | Medicina | es_ES |
dc.relation.publisherversion | https://doi.org/10.3390/cancers12071790 | es_ES |
dc.identifier.doi | 10.3390/cancers12071790 | es_ES |
dc.identifier.publicationfirstpage | 1790-1 | es_ES |
dc.identifier.publicationissue | 7 | es_ES |
dc.identifier.publicationlastpage | 1790-24 | es_ES |
dc.identifier.publicationvolume | 12 | es_ES |
dc.relation.projectID | Gobierno de España. RYC-2012-12104 | es_ES |
dc.relation.projectID | Gobierno de España. PI15/01507 | es_ES |
dc.relation.projectID | Gobierno de España. PI18/00757 | es_ES |
dc.type.version | info:eu-repo/semantics/publishedVersion | en |
dc.rights.cc | Reconocimiento | es_ES |
dc.rights.accessRights | openAccess | en |
dc.authorUAM | Alcalá Sánchez, Sonia (265038) | |
dc.authorUAM | Sáinz Anding, Bruno (264918) | |
dc.facultadUAM | Facultad de Medicina | |