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Deubiquitinylase USP47 Promotes RelA Phosphorylation and Survival in Gastric Cancer Cells
- Source :
- Biomedicines, Vol 6, Iss 2, p 62 (2018), Biomedicines; Volume 6; Issue 2; Pages: 62, Biomedicines
- Publication Year :
- 2018
- Publisher :
- MDPI AG, 2018.
-
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.
- Subjects :
- deubiquitinylases
NF-κB signaling
apoptotic cell death
gastric carcinoma
therapeutic targets
chemoresistance
ubiquitin-specific proteases
0301 basic medicine
Medicine (miscellaneous)
Caspase 3
medicine.disease_cause
Caspase 8
Article
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
Medicine
MTT assay
Viability assay
lcsh:QH301-705.5
Etoposide
business.industry
030104 developmental biology
lcsh:Biology (General)
Cancer cell
Cancer research
business
Carcinogenesis
Camptothecin
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 22279059
- Volume :
- 6
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Biomedicines
- Accession number :
- edsair.doi.dedup.....2ca2322d134fb21d81d715319f167bf3