2. Academic Validation
  3. Inhibition of YB-1 phosphorylation enhances cisplatin activity and disrupts cell division in pleural mesothelioma

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

  • Br J Cancer. 2025 Sep 4. doi: 10.1038/s41416-025-03177-0.
Karin Schelch 1 2,  Nadine Maach 1,  Muhammad Hashim 1,  Benjamin Zitta 1,  Dominik Kirchhofer 1,  Gerald Timelthaler 1,  Anna Solta 2,  Dominik Emminger 1,  Verena Kopatz 3,  Mir A Hoda 2,  Walter Berger 1,  Clemens Aigner 2,  Balazs Dome 2 4 5 6,  Glen Reid 7 8,  Michael Grusch 9
Affiliations

Affiliations

  • 1 Center for Cancer Research, Medical University of Vienna, Vienna, Austria.
  • 2 Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.
  • 3 Department of Radiation Oncology, Applied and Translational Radiobiology, Medical University of Vienna, Vienna, Austria.
  • 4 National Koranyi Institute of Pulmonology, Budapest, Hungary.
  • 5 Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary.
  • 6 Department of Translational Medicine, Lund University, Lund, Sweden.
  • 7 Department of Pathology, Dunedin School of Medicine, Dunedin, New Zealand.
  • 8 The Maurice Wilkins Centre, University of Otago, Dunedin, New Zealand.
  • 9 Center for Cancer Research, Medical University of Vienna, Vienna, Austria. michael.grusch@meduniwien.ac.at.
PMID: 40908296 DOI: 10.1038/s41416-025-03177-0
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 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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