{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T12:37:47Z","timestamp":1787747867109,"version":"build-2784847793"},"reference-count":57,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T00:00:00Z","timestamp":1768608000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats: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.<\/jats:p>","DOI":"10.3390\/antiox15010121","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T08:23:56Z","timestamp":1768811036000},"page":"121","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Reactive Oxygen Species Drive Cell Migration and PD-L1 Expression via YB-1 Phosphorylation in Pleural Mesothelioma"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6262-8176","authenticated-orcid":false,"given":"Muhammad","family":"Hashim","sequence":"first","affiliation":[{"name":"Center for Cancer Research and Comprehensive Cancer Center Vienna, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald","family":"Timelthaler","sequence":"additional","affiliation":[{"name":"Center for Cancer Research and Comprehensive Cancer Center Vienna, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7190-9459","authenticated-orcid":false,"given":"Dominik","family":"Kirchhofer","sequence":"additional","affiliation":[{"name":"Center for Cancer Research and Comprehensive Cancer Center Vienna, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice Irina","family":"Kudlacek","sequence":"additional","affiliation":[{"name":"Center for Cancer Research and Comprehensive Cancer Center Vienna, Medical University of Vienna, 1090 Vienna, 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Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7088-8768","authenticated-orcid":false,"given":"Mir Alireza","family":"Hoda","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina","family":"Grasl-Kraupp","sequence":"additional","affiliation":[{"name":"Center for Cancer Research and Comprehensive Cancer Center Vienna, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8799-8624","authenticated-orcid":false,"given":"Balazs","family":"Dome","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"National Koranyi Institute of Pulmonology, 1121 Budapest, Hungary"},{"name":"Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, 1122 Budapest, Hungary"},{"name":"Department of Translational Medicine, Lund University, 221 00 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0014-1658","authenticated-orcid":false,"given":"Walter","family":"Berger","sequence":"additional","affiliation":[{"name":"Center for Cancer Research and Comprehensive Cancer Center Vienna, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Krupitza","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Schelch","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Comprehensive Cancer Center Vienna, Medical 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