Cytoplasmic accumulation of NCoR in malignant melanoma: consequences of altered gene repression and prognostic significance

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• dc.contributor.author Gallardo Hernández, Fernandoca
• dc.contributor.author Padrón, Andreinaca
• dc.contributor.author Garcia Carbonell, Ricardca
• dc.contributor.author Rius, Cristinaca
• dc.contributor.author González-Pérez, Abelca
• dc.contributor.author Arumí, Montserratca
• dc.contributor.author Iglesias Coma, Marca
• dc.contributor.author Nonell Mazelon, Lara, 1972-ca
• dc.contributor.author Bellosillo Paricio, Beatrizca
• dc.contributor.author Segura Tigell, Soniaca
• dc.contributor.author Pujol Vallverdú, Ramon Mariaca
• dc.contributor.author López Bigas, Núriaca
• dc.contributor.author Bertran, Joanca
• dc.contributor.author Bigas Salvans, Annaca
• dc.contributor.author Espinosa Blay, Lluísca
• dc.date.accessioned 2015-06-10T11:05:29Z
• dc.date.available 2015-06-10T11:05:29Z
• dc.date.issued 2015
• dc.description.abstract Invasive malignant melanoma (MM) is an aggressive tumor with no curative therapy available in advanced stages. Nuclear corepressor (NCoR) is an essential regulator of gene transcription, and its function has been found deregulated in different types of cancer. In colorectal cancer cells, loss of nuclear NCoR is induced by Inhibitor of kappa B kinase (IKK) through the phosphorylation of specific serine residues. We here investigate whether NCoR function impacts in MM, which might have important diagnostic and prognostic significance. By IHC, we here determined the subcellular distribution of NCoR in a cohort of 63 primary invasive MM samples, and analyzed its possible correlation with specific clinical parameters. We therefore used a microarray-based strategy to determine global gene expression differences in samples with similar tumor stage, which differ in the presence of cytoplasmic or nuclear NCoR. We found that loss of nuclear NCoR results in upregulation of a specific cancer-related genetic signature, and is significantly associated with MM progression. Inhibition of IKK activity in melanoma cells reverts NCoR nuclear distribution and specific NCoR-regulated gene transcription. Analysis of public database demonstrated that inactivating NCoR mutations are highly prevalent in MM, showing features of driver oncogene.ca
• dc.description.sponsorship This work was supported by grants from AGAUR (SGR23), RTICCS/FEDER (RD12/0036/0054 and RD12/0036/0044), Spanish Ministry of Economy and Competitiveness (SAF2012-36199) and PI13/00448.
• dc.format.mimetype application/pdfca
• dc.identifier.citation Gallardo F, Padrón A, Garcia-Carbonell R, Rius C, González-Perez A, Arumí-Uria M. et al. Cytoplasmic accumulation of NCoR in malignant melanoma: consequences of altered gene repression and prognostic significance. Oncotarget. 2015 Apr 20;6(11):9284-94. DOI: 10.18632/oncotarget.3252ca
• dc.identifier.doi http://dx.doi.org/10.18632/oncotarget.3252
• dc.identifier.issn 1949-2553
• dc.identifier.uri http://hdl.handle.net/10230/23782
• dc.language.iso engca
• dc.publisher Impact Journalca
• dc.relation.ispartof Oncotarget. 2015 Apr 20;6(11):9284-94
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2012-36199
• dc.rights © Gallardo F. et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License https://creativecommons.org/licenses/by/3.0/, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ca
• dc.rights.accessRights info:eu-repo/semantics/openAccessca
• dc.rights.uri https://creativecommons.org/licenses/by/3.0/ca
• dc.subject.other Melanomaca
• dc.title Cytoplasmic accumulation of NCoR in malignant melanoma: consequences of altered gene repression and prognostic significanceen
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/publishedVersionca