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Título: | Proteomic signature of neuroblastoma cells UKF-NB-4 reveals key role of lysosomal sequestration and the proteasome complex in acquiring chemoresistance to cisplatin |
Autor: | Merlos Rodrigo, Miguel Angel CSIC ORCID; Buchtelova, Hana; Ríos, Vivian de los CSIC ORCID ; Casal, J. Ignacio CSIC ORCID ; Eckschlager, Tomas; Hrabeta, Jan; Belhajova, Marie; Heger, Z.; Adam, Vojtech | Palabras clave: | Neuroblastoma Chemoresistance Cisplatin Lysosomes Proteomics V-ATPases |
Fecha de publicación: | 28-dic-2018 | Editor: | American Chemical Society | Citación: | Journal of Proteome Research 18 (3)1255–1263 (2018) | Resumen: | 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 analysed 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 analysed using nanoLC MS/MS. Among the proteins responsible for UKF-NB-4CDDP chemoresistance, ion channels transport family proteins, ABC superfamily proteins, SLC-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 key mechanisms responsible for intrinsic chemoresistance of neuroblastoma to CDDP. | Descripción: | 28 p.-6 fig. | Versión del editor: | https://doi.org/10.1021/acs.jproteome.8b00867 | URI: | http://hdl.handle.net/10261/173756 | DOI: | 10.1021/acs.jproteome.8b00867 | ISSN: | 1535-3893 | E-ISSN: | 1535-3907 |
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