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

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dc.contributor.author Gallardo Hernández, Fernando
dc.contributor.author Padrón, Andreina
dc.contributor.author Garcia Carbonell, Ricard
dc.contributor.author Rius, Cristina
dc.contributor.author González-Pérez, Abel
dc.contributor.author Arumí, Montserrat
dc.contributor.author Iglesias Coma, Mar
dc.contributor.author Nonell Mazelón, Lara
dc.contributor.author Bellosillo Paricio, Beatriz
dc.contributor.author Segura Tigell, Sonia
dc.contributor.author Pujol Vallverdú, Ramon Maria
dc.contributor.author López Bigas, Núria
dc.contributor.author Bertran, Joan
dc.contributor.author Bigas Salvans, Anna
dc.contributor.author Espinosa Blay, Lluís
dc.date.accessioned 2015-06-10T11:05:29Z
dc.date.available 2015-06-10T11:05:29Z
dc.date.issued 2015
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.3252
dc.identifier.issn 1949-2553
dc.identifier.uri http://hdl.handle.net/10230/23782
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.
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/pdf
dc.language.iso eng
dc.publisher Impact Journal
dc.relation.ispartof Oncotarget. 2015 Apr 20;6(11):9284-94
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.
dc.rights.uri https://creativecommons.org/licenses/by/3.0/
dc.subject.other Melanoma
dc.title Cytoplasmic accumulation of NCoR in malignant melanoma: consequences of altered gene repression and prognostic significance.
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.18632/oncotarget.3252
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2012-36199
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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