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Reactive Oxygen Species Drive Cell Migration and PD-L1 Expression via YB-1 Phosphorylation in Pleural Mesothelioma

Hashim, Muhammad ; Timelthaler, Gerald ; Kirchhofer, Dominik ; Kudlacek, Beatrice Irina ; Mosleh, Berta ; Sinn, Katharina ; Awad, Ezzat Mohamed ; Hoda, Mir Alireza ; Grasl-Kraupp, Bettina and Döme, Balázs LU , et al. (2026) In Antioxidants 15(1).
Abstract

Reactive oxygen species (ROS)-induced aberrant oncogenic signalling has been proposed to mediate the progression and development of pleural mesothelioma (PM). In this study, we demonstrate how ROS promote oncogenic signalling, especially in the context of cell migration and immune evasion via YB-1 phosphorylation in mesothelial and PM cell models. Xanthine (X)- and xanthine oxidase (XO)-generated ROS exposure led to increased migration and a more elongated cell shape in mesothelial and PM cells in live-cell videomicroscopy analyses. These effects were associated with the enhanced phosphorylation of ERK, AKT, and YB-1 and the elevated gene expression of PD-L1 and PD-L2, which were analysed with immunoblotting and quantitative real-time... (More)

Reactive oxygen species (ROS)-induced aberrant oncogenic signalling has been proposed to mediate the progression and development of pleural mesothelioma (PM). In this study, we demonstrate how ROS promote oncogenic signalling, especially in the context of cell migration and immune evasion via YB-1 phosphorylation in mesothelial and PM cell models. Xanthine (X)- and xanthine oxidase (XO)-generated ROS exposure led to increased migration and a more elongated cell shape in mesothelial and PM cells in live-cell videomicroscopy analyses. These effects were associated with the enhanced phosphorylation of ERK, AKT, and YB-1 and the elevated gene expression of PD-L1 and PD-L2, which were analysed with immunoblotting and quantitative real-time RT-PCR, respectively. The pharmacological inhibition of AKT (ipatasertib), MEK (trametinib), and RSK (BI-D1870) resulted in the reversal of ROS-induced effects, with the strongest effects observed upon the inhibition of YB-1 phosphorylation by BI-D1870. The results suggest that ROS exposure has a strong impact on cell migration and immune evasion not only in PM cells but also in mesothelial cells, from which PM arises. Interfering with ROS-responsive kinase pathways, particularly YB-1 phosphorylation, could counteract pro-migratory and immune-evasive effects in PM.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
cell migration, cell signalling, immune checkpoint proteins, pleural mesothelioma, ROS
in
Antioxidants
volume
15
issue
1
article number
121
publisher
MDPI AG
external identifiers
  • scopus:105028629551
  • pmid:41596179
ISSN
2076-3921
DOI
10.3390/antiox15010121
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2026 by the authors.
id
7246ed16-655d-41e3-9116-bb10127a7d93
date added to LUP
2026-02-23 15:29:03
date last changed
2026-02-24 03:00:09
@article{7246ed16-655d-41e3-9116-bb10127a7d93,
  abstract     = {{<p>Reactive oxygen species (ROS)-induced aberrant oncogenic signalling has been proposed to mediate the progression and development of pleural mesothelioma (PM). In this study, we demonstrate how ROS promote oncogenic signalling, especially in the context of cell migration and immune evasion via YB-1 phosphorylation in mesothelial and PM cell models. Xanthine (X)- and xanthine oxidase (XO)-generated ROS exposure led to increased migration and a more elongated cell shape in mesothelial and PM cells in live-cell videomicroscopy analyses. These effects were associated with the enhanced phosphorylation of ERK, AKT, and YB-1 and the elevated gene expression of PD-L1 and PD-L2, which were analysed with immunoblotting and quantitative real-time RT-PCR, respectively. The pharmacological inhibition of AKT (ipatasertib), MEK (trametinib), and RSK (BI-D1870) resulted in the reversal of ROS-induced effects, with the strongest effects observed upon the inhibition of YB-1 phosphorylation by BI-D1870. The results suggest that ROS exposure has a strong impact on cell migration and immune evasion not only in PM cells but also in mesothelial cells, from which PM arises. Interfering with ROS-responsive kinase pathways, particularly YB-1 phosphorylation, could counteract pro-migratory and immune-evasive effects in PM.</p>}},
  author       = {{Hashim, Muhammad and Timelthaler, Gerald and Kirchhofer, Dominik and Kudlacek, Beatrice Irina and Mosleh, Berta and Sinn, Katharina and Awad, Ezzat Mohamed and Hoda, Mir Alireza and Grasl-Kraupp, Bettina and Döme, Balázs and Berger, Walter and Krupitza, Georg and Schelch, Karin and Grusch, Michael}},
  issn         = {{2076-3921}},
  keywords     = {{cell migration; cell signalling; immune checkpoint proteins; pleural mesothelioma; ROS}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{MDPI AG}},
  series       = {{Antioxidants}},
  title        = {{Reactive Oxygen Species Drive Cell Migration and PD-L1 Expression via YB-1 Phosphorylation in Pleural Mesothelioma}},
  url          = {{http://dx.doi.org/10.3390/antiox15010121}},
  doi          = {{10.3390/antiox15010121}},
  volume       = {{15}},
  year         = {{2026}},
}