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dc.contributor.authorAguirre-Portolés, Cristina
dc.contributor.authorFeliú Batlle, Jaime 
dc.contributor.authorReglero Rada, Guillermo J. 
dc.contributor.authorRamírez de Molina, Ana
dc.contributor.otherUAM. Departamento de Medicinaes_ES
dc.contributor.otherInstituto de Investigación Sanitaria Hospital Universitario de La Paz (IdiPAZ)es_ES
dc.date.accessioned2018-11-28T15:24:41Z
dc.date.available2018-11-28T15:24:41Z
dc.date.issued2018-09-17
dc.identifier.citationMolecular Oncology 12.10 (22018): 1735–1752en_US
dc.identifier.issn1574-7891 (print)es_ES
dc.identifier.issn1878-0261 (online)es_ES
dc.identifier.urihttp://hdl.handle.net/10486/685772
dc.description.abstractAt the time of diagnosis, 20% of patients with colorectal cancer present metastasis. Among individuals with primary lesions, 50% of them will develop distant tumours with time. Therefore, early diagnosis and prediction of aggressiveness is crucial for therapy design and disease prognosis. Tumoral cells must undergo significant changes in energy metabolism to meet increased structural and energetic demands for cell proliferation, and metabolic alterations are considered to be a hallmark of cancer. Here, we present the ATP-binding cassette transporter (ABCA1), a regulator of cholesterol transport, as a new marker for invasion and colorectal cancer survival. ABCA1 is significantly overexpressed in patients at advanced stages of colorectal cancer, and its overexpression confers proliferative advantages together with caveolin-1 dependent-increased migratory and invasive capacities. Thus, intracellular cholesterol imbalances mediated by ABCA1 overexpression may contribute to primary tumour growth and dissemination to distant locations. Furthermore, we demonstrate here that increased levels of apolipoprotein A1 (APOA1), a protein involved in cholesterol efflux and high-density lipoprotein constitution, in the extracellular compartment modulates expression of ABCA1 by regulating COX-2, and compensate for ABCA1-dependent excessive export of cholesterol. APOA1 emerges as a new therapeutic option to inhibit the promotion of colorectal cancer to metastasis by modulating intracellular cholesterol metabolism. Furthermore, we propose apabetalone, an orally available small molecule that is currently being evaluated in clinical trials for the treatment of atherosclerosis, as a new putative therapeutic option to prevent colorectal cancer progression by increasing APOA1 expression and regulating reverse transport of cholesterolen_US
dc.description.sponsorshipThis work has been supported by Ministerio de Economía y Competitividad del Gobierno de España (MINECO, Plan Nacional I+D+i AGL2016-76736-C3), Gobierno regional de la Comunidad de Madrid (P2013/ABI-2728, ALIBIRD-CM), EU Structural Funds and AMAROUT-Marie Curie actions (COFUND2014-51539-04)es_ES
dc.format.extent18 pag.es_ES
dc.format.mimetypeapplication/pdfen
dc.language.isoengen
dc.publisherFEBS Press and John Wiley & Sons Ltd.en_US
dc.relation.ispartofMolecular Oncologyen_US
dc.rights© 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.en_US
dc.subject.otherApabetaloneen_US
dc.subject.otherATP-binding cassette transporteren_US
dc.subject.otherColorectal cancer prognosisen_US
dc.subject.otherReverse cholesterol transportes_ES
dc.titleABCA1 overexpression worsens colorectal cancer prognosis by facilitating tumour growth and caveolin-1-dependent invasiveness, and these effects can be ameliorated using the BET inhibitor apabetaloneen_US
dc.typearticleen
dc.subject.ecienciaMedicinaes_ES
dc.relation.publisherversionhttps://doi.org/10.1002/1878-0261.12367es_ES
dc.identifier.doi10.1002/1878-0261.12367es_ES
dc.identifier.publicationfirstpage1735es_ES
dc.identifier.publicationissue10es_ES
dc.identifier.publicationlastpage1752es_ES
dc.identifier.publicationvolume12es_ES
dc.relation.projectIDGobierno de España. AGL2016-76736-C3es_ES
dc.relation.projectIDComunidad de Madrid. P2013/ABI-2728/ALIBIRD-CMes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/228526es_ES
dc.type.versioninfo:eu-repo/semantics/publishedVersionen
dc.rights.ccReconocimientoes_ES
dc.rights.accessRightsopenAccessen
dc.facultadUAMFacultad de Medicina
dc.institutoUAMInstituto de Investigación Sanitaria Hospital Universitario de La Paz (IdiPAZ)


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