Format

Send to

Choose Destination
Oncotarget. 2015 Apr 20;6(11):9284-94.

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

Author information

1
Dermatology Department, Parc de Salut Mar-Hospital del Mar, Barcelona, Spain.
2
Pathology Department, Parc de Salut Mar-Hospital del Mar, Barcelona, Spain.
3
Stem Cells and Cancer Research Laboratory, Institut Hospital del Mar Investigacions Mèdiques (IMIM), Barcelona, Spain.
4
Research Unit on Biomedical Informatics, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
5
Servei d'Anàlisi de Microarrays, Institut Hospital del Mar Investigacions Mèdiques (IMIM), Barcelona, Spain.
6
Catalan Institution for Research and Advanced Studies (ICREA), Passeig Lluís Companys, Barcelona, Spain.
7
Universitat de Vic, Universitat Central de Catalunya (UVic-UCC), Vic, Spain.

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.

KEYWORDS:

IKK; NCoR; gene transcription; melanoma progression

PMID:
25823659
PMCID:
PMC4496217
DOI:
10.18632/oncotarget.3252
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Impact Journals, LLC Icon for PubMed Central
Loading ...
Support Center