Detail publikačního výsledku

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.

Originální název

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

Anglický název

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

Druh

Článek WoS

Originální abstrakt

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.

Anglický abstrakt

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.

Klíčová slova

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

Klíčová slova v angličtině

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

Autoři

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

Rok RIV

2019

Vydáno

25.03.2019

Nakladatel

American Chemical Society

ISSN

1535-3893

Periodikum

JOURNAL OF PROTEOME RESEARCH

Svazek

18

Číslo

3

Stát

Spojené státy americké

Strany od

1255

Strany do

1263

Strany počet

9

URL

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

Plný text v Digitální knihovně

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"
}

Dokumenty

Proteomic signature of neuroblastoma cells UKF-NB-4 reveals key role of lysosomal sequestration
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