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Deubiquitinylase USP47 Promotes RelA Phosphorylation and Survival in Gastric Cancer Cells

Every year, gastric cancer causes around 819,000 deaths worldwide. The incidence of gastric cancer in the western world is slowly declining, but the prognosis is unpromising. In Germany, the 5-year-survival rate is around 32%, and the average life span after diagnosis is 6 to 9 months. Therapy of ga...

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Autores principales: Naghavi, Lara, Schwalbe, Martin, Ghanem, Ahmed, Naumann, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6027160/
https://www.ncbi.nlm.nih.gov/pubmed/29786670
http://dx.doi.org/10.3390/biomedicines6020062
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author Naghavi, Lara
Schwalbe, Martin
Ghanem, Ahmed
Naumann, Michael
author_facet Naghavi, Lara
Schwalbe, Martin
Ghanem, Ahmed
Naumann, Michael
author_sort Naghavi, Lara
collection PubMed
description Every year, gastric cancer causes around 819,000 deaths worldwide. The incidence of gastric cancer in the western world is slowly declining, but the prognosis is unpromising. In Germany, the 5-year-survival rate is around 32%, and the average life span after diagnosis is 6 to 9 months. Therapy of gastric cancer patients comprises a gastrectomy and perioperative or adjuvant chemotherapy. However, resistance of gastric cancer cells to these agents is widespread; thus, improved chemotherapeutic approaches are required. Nuclear factor kappa B (NF-κB) transcription factors are associated with anti-apoptosis, carcinogenesis, and chemoresistance, and thus, constitute attractive targets for therapeutic intervention. In immunoblots, we show that ubiquitin specific protease 47 (USP47) promotes β-transducin repeat-containing protein (βTrCP) stability and phosphorylation of RelA. Furthermore, after knockdown of USP47 by RNA interference, we analyzed in gastric cancer cell lines metabolic activity/viability in an MTT assay, and apoptotic cell death by Annexin V staining and poly(ADP-Ribose) polymerase (PARP)-1, caspase 3, and caspase 8 cleavage, respectively. We found that USP47 contributes to cell viability and chemoresistance in NCI-N87 gastric carcinoma cells treated with etoposide and camptothecin. Inhibition of USP47 might be a suitable strategy to downregulate NF-κB activity, and to overcome chemoresistance in gastric cancer.
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spelling pubmed-60271602018-07-13 Deubiquitinylase USP47 Promotes RelA Phosphorylation and Survival in Gastric Cancer Cells Naghavi, Lara Schwalbe, Martin Ghanem, Ahmed Naumann, Michael Biomedicines Article Every year, gastric cancer causes around 819,000 deaths worldwide. The incidence of gastric cancer in the western world is slowly declining, but the prognosis is unpromising. In Germany, the 5-year-survival rate is around 32%, and the average life span after diagnosis is 6 to 9 months. Therapy of gastric cancer patients comprises a gastrectomy and perioperative or adjuvant chemotherapy. However, resistance of gastric cancer cells to these agents is widespread; thus, improved chemotherapeutic approaches are required. Nuclear factor kappa B (NF-κB) transcription factors are associated with anti-apoptosis, carcinogenesis, and chemoresistance, and thus, constitute attractive targets for therapeutic intervention. In immunoblots, we show that ubiquitin specific protease 47 (USP47) promotes β-transducin repeat-containing protein (βTrCP) stability and phosphorylation of RelA. Furthermore, after knockdown of USP47 by RNA interference, we analyzed in gastric cancer cell lines metabolic activity/viability in an MTT assay, and apoptotic cell death by Annexin V staining and poly(ADP-Ribose) polymerase (PARP)-1, caspase 3, and caspase 8 cleavage, respectively. We found that USP47 contributes to cell viability and chemoresistance in NCI-N87 gastric carcinoma cells treated with etoposide and camptothecin. Inhibition of USP47 might be a suitable strategy to downregulate NF-κB activity, and to overcome chemoresistance in gastric cancer. MDPI 2018-05-22 /pmc/articles/PMC6027160/ /pubmed/29786670 http://dx.doi.org/10.3390/biomedicines6020062 Text en © 2018 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
Naghavi, Lara
Schwalbe, Martin
Ghanem, Ahmed
Naumann, Michael
Deubiquitinylase USP47 Promotes RelA Phosphorylation and Survival in Gastric Cancer Cells
title Deubiquitinylase USP47 Promotes RelA Phosphorylation and Survival in Gastric Cancer Cells
title_full Deubiquitinylase USP47 Promotes RelA Phosphorylation and Survival in Gastric Cancer Cells
title_fullStr Deubiquitinylase USP47 Promotes RelA Phosphorylation and Survival in Gastric Cancer Cells
title_full_unstemmed Deubiquitinylase USP47 Promotes RelA Phosphorylation and Survival in Gastric Cancer Cells
title_short Deubiquitinylase USP47 Promotes RelA Phosphorylation and Survival in Gastric Cancer Cells
title_sort deubiquitinylase usp47 promotes rela phosphorylation and survival in gastric cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6027160/
https://www.ncbi.nlm.nih.gov/pubmed/29786670
http://dx.doi.org/10.3390/biomedicines6020062
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