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Role of Dusp6 Phosphatase as a Tumor Suppressor in Non-Small Cell Lung Cancer

DUSP6/MKP3 is a dual-specific phosphatase that regulates extracellular regulated kinase ERK1/2 and ERK5 activity, with an increasingly recognized role as tumor suppressor. In silico studies from Gene expression Omnibus (GEO) and Cancer Genome atlas (TCGA) databases reveal poor prognosis in those Non...

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Autores principales: Moncho-Amor, Verónica, Pintado-Berninches, Laura, Ibañez de Cáceres, Inmaculada, Martín-Villar, Ester, Quintanilla, Miguel, Chakravarty, Probir, Cortes-Sempere, María, Fernández-Varas, Beatriz, Rodriguez-Antolín, Carlos, de Castro, Javier, Sastre, Leandro, Perona, Rosario
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6514584/
https://www.ncbi.nlm.nih.gov/pubmed/31027181
http://dx.doi.org/10.3390/ijms20082036
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author Moncho-Amor, Verónica
Pintado-Berninches, Laura
Ibañez de Cáceres, Inmaculada
Martín-Villar, Ester
Quintanilla, Miguel
Chakravarty, Probir
Cortes-Sempere, María
Fernández-Varas, Beatriz
Rodriguez-Antolín, Carlos
de Castro, Javier
Sastre, Leandro
Perona, Rosario
author_facet Moncho-Amor, Verónica
Pintado-Berninches, Laura
Ibañez de Cáceres, Inmaculada
Martín-Villar, Ester
Quintanilla, Miguel
Chakravarty, Probir
Cortes-Sempere, María
Fernández-Varas, Beatriz
Rodriguez-Antolín, Carlos
de Castro, Javier
Sastre, Leandro
Perona, Rosario
author_sort Moncho-Amor, Verónica
collection PubMed
description DUSP6/MKP3 is a dual-specific phosphatase that regulates extracellular regulated kinase ERK1/2 and ERK5 activity, with an increasingly recognized role as tumor suppressor. In silico studies from Gene expression Omnibus (GEO) and Cancer Genome atlas (TCGA) databases reveal poor prognosis in those Non-small cell lung cancer (NSCLC) patients with low expression levels of DUSP6. In agreement with these data, here we show that DUSP6 plays a major role in the regulation of cell migration, motility and tumor growth. We have found upregulation in the expression of several genes involved in epithelial to mesenchymal transition (EMT) in NSCLC-DUSP6 depleted cells. Data obtained in RNA-seq studies carried out in DUSP6 depleted cells identified EGFR, TGF-β and WNT signaling pathways and several genes such as VAV3, RUNXR2, LEF1, FGFR2 whose expression is upregulated in these cells and therefore affecting cellular functions such as integrin mediated cell adhesion, focal adhesion and motility. Furthermore, EGF signaling pathway is activated via ERK5 and not ERK1/2 and TGF-β via SMAD2/3 in DUSP6 depleted cells. In summary DUSP6 is a tumor suppressor in NSCLC and re-establishment of its expression may be a potential strategy to revert poor outcome in NSCLC patients.
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spelling pubmed-65145842019-05-30 Role of Dusp6 Phosphatase as a Tumor Suppressor in Non-Small Cell Lung Cancer Moncho-Amor, Verónica Pintado-Berninches, Laura Ibañez de Cáceres, Inmaculada Martín-Villar, Ester Quintanilla, Miguel Chakravarty, Probir Cortes-Sempere, María Fernández-Varas, Beatriz Rodriguez-Antolín, Carlos de Castro, Javier Sastre, Leandro Perona, Rosario Int J Mol Sci Article DUSP6/MKP3 is a dual-specific phosphatase that regulates extracellular regulated kinase ERK1/2 and ERK5 activity, with an increasingly recognized role as tumor suppressor. In silico studies from Gene expression Omnibus (GEO) and Cancer Genome atlas (TCGA) databases reveal poor prognosis in those Non-small cell lung cancer (NSCLC) patients with low expression levels of DUSP6. In agreement with these data, here we show that DUSP6 plays a major role in the regulation of cell migration, motility and tumor growth. We have found upregulation in the expression of several genes involved in epithelial to mesenchymal transition (EMT) in NSCLC-DUSP6 depleted cells. Data obtained in RNA-seq studies carried out in DUSP6 depleted cells identified EGFR, TGF-β and WNT signaling pathways and several genes such as VAV3, RUNXR2, LEF1, FGFR2 whose expression is upregulated in these cells and therefore affecting cellular functions such as integrin mediated cell adhesion, focal adhesion and motility. Furthermore, EGF signaling pathway is activated via ERK5 and not ERK1/2 and TGF-β via SMAD2/3 in DUSP6 depleted cells. In summary DUSP6 is a tumor suppressor in NSCLC and re-establishment of its expression may be a potential strategy to revert poor outcome in NSCLC patients. MDPI 2019-04-25 /pmc/articles/PMC6514584/ /pubmed/31027181 http://dx.doi.org/10.3390/ijms20082036 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Moncho-Amor, Verónica
Pintado-Berninches, Laura
Ibañez de Cáceres, Inmaculada
Martín-Villar, Ester
Quintanilla, Miguel
Chakravarty, Probir
Cortes-Sempere, María
Fernández-Varas, Beatriz
Rodriguez-Antolín, Carlos
de Castro, Javier
Sastre, Leandro
Perona, Rosario
Role of Dusp6 Phosphatase as a Tumor Suppressor in Non-Small Cell Lung Cancer
title Role of Dusp6 Phosphatase as a Tumor Suppressor in Non-Small Cell Lung Cancer
title_full Role of Dusp6 Phosphatase as a Tumor Suppressor in Non-Small Cell Lung Cancer
title_fullStr Role of Dusp6 Phosphatase as a Tumor Suppressor in Non-Small Cell Lung Cancer
title_full_unstemmed Role of Dusp6 Phosphatase as a Tumor Suppressor in Non-Small Cell Lung Cancer
title_short Role of Dusp6 Phosphatase as a Tumor Suppressor in Non-Small Cell Lung Cancer
title_sort role of dusp6 phosphatase as a tumor suppressor in non-small cell lung cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6514584/
https://www.ncbi.nlm.nih.gov/pubmed/31027181
http://dx.doi.org/10.3390/ijms20082036
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