Proteomic Signature of Neuroblastoma Cells UKF-NB-4 Reveals Key Role of Lysosomal Sequestration and the Proteasome Complex in Acquiring Chemoresistance to Cisplatin
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- Keywords
- V-ATPases, chemoresistance, cisplatin, lysosomes, neuroblastoma, proteomics,
- MeSH
- Apoptosis drug effects MeSH
- Drug Resistance, Neoplasm genetics MeSH
- Cisplatin adverse effects pharmacology MeSH
- Humans MeSH
- Lysosomes genetics MeSH
- Cell Line, Tumor MeSH
- Neuroblastoma drug therapy genetics pathology MeSH
- Cell Proliferation drug effects MeSH
- Proteasome Endopeptidase Complex genetics MeSH
- Proteomics * MeSH
- Gene Expression Regulation, Neoplastic genetics MeSH
- Transcriptome genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Cisplatin MeSH
- Proteasome Endopeptidase Complex MeSH
Cisplatin (CDDP) is a widely used agent in the treatment of neuroblastoma. Unfortunately, the development of acquired chemoresistance limits its clinical use. To gain a detailed understanding of the mechanisms underlying the development of such chemoresistance, we comparatively analyzed established cisplatin-resistant neuroblastoma cell line (UKF-NB-4CDDP) and its sensitive counterpart (UKF-NB-4). First, using viability screenings, we confirmed the decreased sensitivity of tested cells to cisplatin and identified a cross-resistance to carboplatin and oxaliplatin. Then, the proteomic signatures were analyzed using nano liquid chromatography with tandem mass spectrometry. Among the proteins responsible for UKF-NB-4CDDP chemoresistance, ion channels transport family proteins, ATP-binding cassette superfamily proteins (ATP = adenosine triphosphate), solute carrier-mediated trans-membrane transporters, proteasome complex subunits, and V-ATPases were identified. Moreover, we detected markedly higher proteasome activity in UKF-NB-4CDDP cells and a remarkable lysosomal enrichment that can be inhibited by bafilomycin A to sensitize UKF-NB-4CDDP to CDDP. Our results indicate that lysosomal sequestration and proteasome activity may be one of the key mechanisms responsible for intrinsic chemoresistance of neuroblastoma to CDDP.
References provided by Crossref.org
Metallothionein-3 promotes cisplatin chemoresistance remodelling in neuroblastoma
