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Integrative Analysis of Transcriptomics and Clinical Data Uncovers the Tumor- Suppressive Activity of MITF in Prostate Cancer
dc.contributor.author | Valcárcel Jiménez, Lorea | |
dc.contributor.author | Macchia, Alice | |
dc.contributor.author | Martín Martín, Natalia | |
dc.contributor.author | Cortázar, Ana Rosa | |
dc.contributor.author | Schaub Clerigué, Ariane | |
dc.contributor.author | Pujana Vaquerizo, Mikel | |
dc.contributor.author | Fernández Ruiz, Sonia | |
dc.contributor.author | Lacasa Viscasillas, Isabel | |
dc.contributor.author | Santos Martín, Aida | |
dc.contributor.author | Loizaga Iriarte, Ana | |
dc.contributor.author | Unda Urzaiz, Jesús Miguel | |
dc.contributor.author | Hermanova, Ivana | |
dc.contributor.author | Astobiza Pérez, Janire | |
dc.contributor.author | Graupera, Mariona | |
dc.contributor.author | Julia, Starkova | |
dc.contributor.author | Sutherland, James D. | |
dc.contributor.author | Barrio Olano, María Rosa | |
dc.contributor.author | Aransay Bañares, Ana María | |
dc.contributor.author | Carracedo Pérez, Arkaitz | |
dc.contributor.author | Torrano Moya, Verónica | |
dc.date.accessioned | 2018-12-14T09:42:22Z | |
dc.date.available | 2018-12-14T09:42:22Z | |
dc.date.issued | 2018-10-11 | |
dc.identifier.citation | Cell Death & Disease 9 : (2018) // Article ID 1041 | es_ES |
dc.identifier.issn | 2041-4889 | |
dc.identifier.uri | http://hdl.handle.net/10810/30345 | |
dc.description.abstract | The dysregulation of gene expression is an enabling hallmark of cancer. Computational analysis of transcriptomics data from human cancer specimens, complemented with exhaustive clinical annotation, provides an opportunity to identify core regulators of the tumorigenic process. Here we exploit well-annotated clinical datasets of prostate cancer for the discovery of transcriptional regulators relevant to prostate cancer. Following this rationale, we identify Microphthalmia-associated transcription factor (MITF) as a prostate tumor suppressor among a subset of transcription factors. Importantly, we further interrogate transcriptomics and clinical data to refine MITF perturbation-based empirical assays and unveil Crystallin Alpha B (CRYAB) as an unprecedented direct target of the transcription factor that is, at least in part, responsible for its tumor-suppressive activity in prostate cancer. This evidence was supported by the enhanced prognostic potential of a signature based on the concomitant alteration of MITF and CRYAB in prostate cancer patients. In sum, our study provides proof-of-concept evidence of the potential of the bioinformatics screen of publicly available cancer patient databases as discovery platforms, and demonstrates that the MITF-CRYAB axis controls prostate cancer biology. | es_ES |
dc.description.sponsorship | The work of V. Torrano is funded by Fundacion Vasca de Innovacion e Investigacion Sanitarias, BIOEF (BIO15/CA/052), the AECC J.P. Bizkaia and the Basque Department of Health (2016111109). The work of A. Carracedo is supported by the Basque Department of Industry, Tourism and Trade (Etortek) and the Department of Education (IKERTALDE IT1106-16, also participated by A. Gomez-Munoz), the BBVA Foundation, the MINECO (SAF2016-79381-R (FEDER/EU); Severo Ochoa Excellence Accreditation SEV-2016-0644; Excellence Networks SAF2016-81975-REDT), European Training Networks Project (H2020-MSCA-ITN-308 2016 721532), the AECC IDEAS16 (IDEAS175CARR) and the European Research Council (Starting Grant 336343, PoC 754627). CIBERONC was co-funded with FEDER funds. The work of M. Graupera is supported by the MINECO (SAF2014-59950-P). The work of A. Aransay is supported by the Basque Department of Industry, Tourism and Trade (Etortek and Elkartek Programs), the Innovation Technology Department of Bizkaia County, CIBERehd Network and Spanish MINECO the Severo Ochoa Excellence Accreditation (SEV-2016-0644). R. Barrio acknowledges Spanish MINECO (BFU2014-52282-P, Consolider BFU2014-57703-REDC), the Departments of Education and Industry of the Basque Government (PI2012/42) and the Bizkaia County. J. Starkova acknowledges the Ministry of Health of Czech Republic AZV NV15-28848A. We are thankful to the Basque Biobank for Research (BIOEF) for the custody and management of human prostate specimens used in this study. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Nature Publishing Group | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/SAF2016-79381-R | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/SEV-2016-0644 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/BFU2014-52282-P | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/BFU2014-57703-REDC | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/SAF2016-81975-REDT | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/SAF2014-59950-P | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | alpha-B-crystallin | es_ES |
dc.subject | breast-cancer | es_ES |
dc.subject | malignant-melanoma | es_ES |
dc.subject | colorectal-cancer | es_ES |
dc.subject | induced apoptosis | es_ES |
dc.subject | progression | es_ES |
dc.subject | expression | es_ES |
dc.subject | cells | es_ES |
dc.subject | PGC1-alpha | es_ES |
dc.subject | proliferation | es_ES |
dc.title | Integrative Analysis of Transcriptomics and Clinical Data Uncovers the Tumor- Suppressive Activity of MITF in Prostate Cancer | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. | es_ES |
dc.rights.holder | Atribución 3.0 España | * |
dc.relation.publisherversion | https://www.nature.com/articles/s41419-018-1096-6 | es_ES |
dc.identifier.doi | 10.1038/s41419-018-1096-6 | |
dc.departamentoes | Bioquímica y biología molecular | es_ES |
dc.departamentoes | Cirugía, radiología y medicina física | es_ES |
dc.departamentoeu | Biokimika eta biologia molekularra | es_ES |
dc.departamentoeu | Kirurgia,erradiologia eta medikuntza fisikoa | es_ES |
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