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Inhibition of YB-1 phosphorylation enhances cisplatin activity and disrupts cell division in pleural mesothelioma

Schelch, Karin ; Maach, Nadine ; Hashim, Muhammad ; Zitta, Benjamin ; Kirchhofer, Dominik ; Timelthaler, Gerald ; Solta, Anna ; Emminger, Dominik ; Kopatz, Verena and Hoda, Mir A. , et al. (2025) In British Journal of Cancer 133(9). p.1391-1400
Abstract

Background: The cold-shock domain protein YB-1 is overexpressed in pleural mesothelioma (PM) and was shown to contribute to increased cell migration and platinum resistance. Methods: Phosphorylation of YB-1 at position serine 102 was analysed by immunohistochemistry, immunofluorescence and immunoblotting in PM tissue specimens and cell lines. Intracellular localisation experiments involved immunoblotting, transfection of fluorescent protein-tagged YB-1 and confocal imaging. YB-1 phosphorylation was inhibited with the RSK inhibitors BI-D1870 and LJH685. Effects of inhibition alone and in combination with radiation or cisplatin treatment were analysed by cell viability assays, clonogenic assays and videomicroscopy-based migration and cell... (More)

Background: The cold-shock domain protein YB-1 is overexpressed in pleural mesothelioma (PM) and was shown to contribute to increased cell migration and platinum resistance. Methods: Phosphorylation of YB-1 at position serine 102 was analysed by immunohistochemistry, immunofluorescence and immunoblotting in PM tissue specimens and cell lines. Intracellular localisation experiments involved immunoblotting, transfection of fluorescent protein-tagged YB-1 and confocal imaging. YB-1 phosphorylation was inhibited with the RSK inhibitors BI-D1870 and LJH685. Effects of inhibition alone and in combination with radiation or cisplatin treatment were analysed by cell viability assays, clonogenic assays and videomicroscopy-based migration and cell fate map analyses. Results: YB-1 phosphorylated at serine 102 is present in PM cell lines and tissue. Inhibition of phosphorylation with BI-D1870 reduced YB-1 localisation in the cell nucleus and led to reduced cell viability, clonogenicity, migration and disrupted cell division. Moreover, exposure to BI-D1870 increased the effect of radiation and cisplatin treatment with additive to synergistic effects in PM cell lines and primary cultures. Conclusions: The serine 102 phosphorylated form of YB-1 contributes to the malignant phenotype of PM. Inhibition of YB-1 phosphorylation warrants further exploration as part of treatment strategies for this devastating disease.

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type
Contribution to journal
publication status
published
subject
in
British Journal of Cancer
volume
133
issue
9
pages
10 pages
publisher
Nature Publishing Group
external identifiers
  • pmid:40908296
  • scopus:105015166704
ISSN
0007-0920
DOI
10.1038/s41416-025-03177-0
language
English
LU publication?
yes
id
a913c2cb-7d3a-405b-92ab-c15b8d783727
date added to LUP
2025-11-14 13:11:15
date last changed
2025-11-15 03:00:06
@article{a913c2cb-7d3a-405b-92ab-c15b8d783727,
  abstract     = {{<p>Background: The cold-shock domain protein YB-1 is overexpressed in pleural mesothelioma (PM) and was shown to contribute to increased cell migration and platinum resistance. Methods: Phosphorylation of YB-1 at position serine 102 was analysed by immunohistochemistry, immunofluorescence and immunoblotting in PM tissue specimens and cell lines. Intracellular localisation experiments involved immunoblotting, transfection of fluorescent protein-tagged YB-1 and confocal imaging. YB-1 phosphorylation was inhibited with the RSK inhibitors BI-D1870 and LJH685. Effects of inhibition alone and in combination with radiation or cisplatin treatment were analysed by cell viability assays, clonogenic assays and videomicroscopy-based migration and cell fate map analyses. Results: YB-1 phosphorylated at serine 102 is present in PM cell lines and tissue. Inhibition of phosphorylation with BI-D1870 reduced YB-1 localisation in the cell nucleus and led to reduced cell viability, clonogenicity, migration and disrupted cell division. Moreover, exposure to BI-D1870 increased the effect of radiation and cisplatin treatment with additive to synergistic effects in PM cell lines and primary cultures. Conclusions: The serine 102 phosphorylated form of YB-1 contributes to the malignant phenotype of PM. Inhibition of YB-1 phosphorylation warrants further exploration as part of treatment strategies for this devastating disease.</p>}},
  author       = {{Schelch, Karin and Maach, Nadine and Hashim, Muhammad and Zitta, Benjamin and Kirchhofer, Dominik and Timelthaler, Gerald and Solta, Anna and Emminger, Dominik and Kopatz, Verena and Hoda, Mir A. and Berger, Walter and Aigner, Clemens and Dome, Balazs and Reid, Glen and Grusch, Michael}},
  issn         = {{0007-0920}},
  language     = {{eng}},
  number       = {{9}},
  pages        = {{1391--1400}},
  publisher    = {{Nature Publishing Group}},
  series       = {{British Journal of Cancer}},
  title        = {{Inhibition of YB-1 phosphorylation enhances cisplatin activity and disrupts cell division in pleural mesothelioma}},
  url          = {{http://dx.doi.org/10.1038/s41416-025-03177-0}},
  doi          = {{10.1038/s41416-025-03177-0}},
  volume       = {{133}},
  year         = {{2025}},
}