Publication detail

Proteomic signature of neuroblastoma cells UKF-NB-4 reveals key role of lysosomal sequestration and the proteasome complex in acquiring chemoresistance to cisplatin

MERLOS RODRIGO, M. BUCHTELOVÁ, H. DE LOS RIOS, V. CASAL ÁLVAREZ, J. ECKSCHLAGER, T. HRABĚTA, J. BELHAJOVÁ, M. HEGER, Z. ADAM, V.

Original Title

Proteomic signature of neuroblastoma cells UKF-NB-4 reveals key role of lysosomal sequestration and the proteasome complex in acquiring chemoresistance to cisplatin

Type

journal article in Web of Science

Language

English

Original Abstract

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-4(CDDP)) 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-4(CDDP) 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-4(CDDP) cells and a remarkable lysosomal enrichment that can be inhibited by bafilomycin A to sensitize UKF-NB-4(CDDP) 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.

Keywords

neuroblastoma; chemoresistance; cisplatin; lysosomes; proteomics; V-ATPases

Authors

MERLOS RODRIGO, M.; BUCHTELOVÁ, H.; DE LOS RIOS, V.; CASAL ÁLVAREZ, J.; ECKSCHLAGER, T.; HRABĚTA, J.; BELHAJOVÁ, M.; HEGER, Z.; ADAM, V.

Released

25. 3. 2019

Publisher

American Chemical Society

ISBN

1535-3893

Periodical

JOURNAL OF PROTEOME RESEARCH

Year of study

18

Number

3

State

United States of America

Pages from

1255

Pages to

1263

Pages count

9

URL

https://pubs.acs.org/doi/10.1021/acs.jproteome.8b00867

Full text in the Digital Library

http://hdl.handle.net/11012/195620

BibTex

@article{BUT156373,
  author="Miguel Ángel {Merlos Rodrigo} and Hana {Michálková} and Vivian {De los Rios} and José Ignacio {Casal Álvarez} and Tomáš {Eckschlager} and Jan {Hraběta} and Marie {Belhajová} and Zbyněk {Heger} and Vojtěch {Adam}",
  title="Proteomic signature of neuroblastoma cells UKF-NB-4 reveals key role of lysosomal sequestration and the proteasome complex in acquiring chemoresistance to cisplatin",
  journal="JOURNAL OF PROTEOME RESEARCH",
  year="2019",
  volume="18",
  number="3",
  pages="1255--1263",
  doi="10.1021/acs.jproteome.8b00867",
  issn="1535-3893",
  url="https://pubs.acs.org/doi/10.1021/acs.jproteome.8b00867"
}