RKIP Regulates Differentiation-Related Features in Melanocytic Cells
dc.contributor.author | Penas Lago, Cristina | |
dc.contributor.author | Apraiz García, Aintzane | |
dc.contributor.author | Muñoa Hoyos, Iraia | |
dc.contributor.author | Arroyo Berdugo, Yoana | |
dc.contributor.author | Rasero, Javier | |
dc.contributor.author | Ezcurra García Unzueta, Pilar Ariadna | |
dc.contributor.author | Velasco, Verónica | |
dc.contributor.author | Subirán Ciudad, Nerea | |
dc.contributor.author | Bosserhoff, Anja K. | |
dc.contributor.author | Alonso Alegre, Santos | |
dc.contributor.author | Asumendi Mallea, Aintzane | |
dc.contributor.author | Boyano López, María Dolores | |
dc.date.accessioned | 2020-07-02T09:37:17Z | |
dc.date.available | 2020-07-02T09:37:17Z | |
dc.date.issued | 2020-06-03 | |
dc.identifier.citation | Cancers 12(6) : (2020) // Article ID 1451 | es_ES |
dc.identifier.issn | 2072-6694, | |
dc.identifier.uri | http://hdl.handle.net/10810/44809 | |
dc.description.abstract | Raf Kinase Inhibitor Protein (RKIP) has been extensively reported as an inhibitor of keysignaling pathways involved in the aggressive tumor phenotype and shows decreased expressionin several types of cancers. However, little is known about RKIP in melanoma or regarding its functionin normal cells. We examined the role of RKIP in both primary melanocytes and malignant melanomacells and evaluated its diagnostic and prognostic value. IHC analysis revealed a significantly higherexpression of RKIP in nevi compared with early-stage (stage I–II, AJCC 8th) melanoma biopsies.Proliferation, wound healing, and collagen-coated transwell assays uncovered the implication ofRKIP on the motility but not on the proliferative capacity of melanoma cells as RKIP protein levelswere inversely correlated with the migration capacity of both primary and metastatic melanoma cellsbut did not alter other parameters. As shown by RNA sequencing, endogenous RKIP knockdownin primary melanocytes triggered the deregulation of cellular differentiation-related processes,including genes (i.e., ZEB1, THY-1) closely related to the EMT. Interestingly, NANOG was identifiedas a putative transcriptional regulator of many of the deregulated genes, and RKIP was able todecrease the activation of the NANOG promoter. As a whole, our data support the utility of RKIPas a diagnostic marker for early-stage melanomas. In addition, these findings indicate its participationin the maintenance of a differentiated state of melanocytic cells by modulating genes intimately linkedto the cellular motility and explain the progressive decrease of RKIP often described in tumors. | es_ES |
dc.description.sponsorship | This project was supported by grants from the Basque Government (KK2016-036 and KK2017-041 toM.D.B.), UPV/EHU (GIU17/066 to M.D.B.), H2020-ESCEL JTI (15/01 to M.D.B.) and MINECO (PCIN-2015-241 toM.D.B.). CP holds a predoctoral fellowship from the Basque Government | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | MDPI | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/PCIN-2015-241 to M.D.B. | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | |
dc.subject | RKIP | es_ES |
dc.subject | melanocytes | es_ES |
dc.subject | melanoma | es_ES |
dc.subject | transcriptome analysis | es_ES |
dc.subject | cell motility | es_ES |
dc.subject | differentiation | es_ES |
dc.subject | biomarke | es_ES |
dc.title | RKIP Regulates Differentiation-Related Features in Melanocytic Cells | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.date.updated | 2020-06-30T16:26:48Z | |
dc.rights.holder | 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open accessarticle distributed under the terms and conditions of the Creative Commons Attribution(CC BY) license (http://creativecommons.org/licenses/by/4.0/). | es_ES |
dc.relation.publisherversion | https://www.mdpi.com/2072-6694/12/6/1451/review_report | es_ES |
dc.identifier.doi | 10.3390/cancers12061451 | |
dc.departamentoes | Genética, antropología física y fisiología animal | |
dc.departamentoes | Biología celular e histología | |
dc.departamentoeu | Genetika,antropologia fisikoa eta animalien fisiologia | |
dc.departamentoeu | Zelulen biologia eta histologia |
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Except where otherwise noted, this item's license is described as 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open accessarticle distributed under the terms and conditions of the Creative Commons Attribution(CC BY) license (http://creativecommons.org/licenses/by/4.0/).