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Biomedicines 2018, 6(2), 62; https://doi.org/10.3390/biomedicines6020062

Deubiquitinylase USP47 Promotes RelA Phosphorylation and Survival in Gastric Cancer Cells

Institute of Experimental Internal Medicine, Otto von Guericke University, 39120 Magdeburg, Germany
These authors contributed equally to this work.
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Received: 13 February 2018 / Revised: 11 May 2018 / Accepted: 12 May 2018 / Published: 22 May 2018
(This article belongs to the Special Issue Roles of NF-κB in Cancer and Their Therapeutic Approaches)
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Abstract

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. View Full-Text
Keywords: deubiquitinylases; NF-κB signaling; apoptotic cell death; gastric carcinoma; therapeutic targets; chemoresistance; ubiquitin-specific proteases deubiquitinylases; NF-κB signaling; apoptotic cell death; gastric carcinoma; therapeutic targets; chemoresistance; ubiquitin-specific proteases
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Naghavi, L.; Schwalbe, M.; Ghanem, A.; Naumann, M. Deubiquitinylase USP47 Promotes RelA Phosphorylation and Survival in Gastric Cancer Cells. Biomedicines 2018, 6, 62.

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