YB-1 regulates mesothelioma cell migration via snail but not EGFR, MMP1, EPHA5 or PARK2.

Autor: Schelch K; Center for Cancer Research and Comprehensive Cancer Center, Medical University of Vienna, Austria.; Department of Thoracic Surgery, Medical University of Vienna, Austria., Eder S; Center for Cancer Research and Comprehensive Cancer Center, Medical University of Vienna, Austria., Zitta B; Center for Cancer Research and Comprehensive Cancer Center, Medical University of Vienna, Austria., Phimmachanh M; Center for Cancer Research and Comprehensive Cancer Center, Medical University of Vienna, Austria.; University of Technology Sydney, NSW, Australia., Johnson TG; Center for Cancer Research and Comprehensive Cancer Center, Medical University of Vienna, Austria.; The University of Sydney, NSW, Australia., Emminger D; Center for Cancer Research and Comprehensive Cancer Center, Medical University of Vienna, Austria., Wenninger-Weinzierl A; St. Anna Children's Cancer Research Institute, Innovative Cancer Models, Vienna, Austria., Sturtzel C; St. Anna Children's Cancer Research Institute, Innovative Cancer Models, Vienna, Austria., Poplimont H; St. Anna Children's Cancer Research Institute, Innovative Cancer Models, Vienna, Austria., Ries A; Center for Cancer Research and Comprehensive Cancer Center, Medical University of Vienna, Austria., Hoetzenecker K; Department of Thoracic Surgery, Medical University of Vienna, Austria., Hoda MA; Department of Thoracic Surgery, Medical University of Vienna, Austria., Berger W; Center for Cancer Research and Comprehensive Cancer Center, Medical University of Vienna, Austria., Distel M; St. Anna Children's Cancer Research Institute, Innovative Cancer Models, Vienna, Austria., Dome B; Department of Thoracic Surgery, Medical University of Vienna, Austria.; National Koranyi Institute of Pulmonology, Budapest, Hungary.; Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary., Reid G; Department of Pathology, Dunedin School of Medicine, New Zealand.; The Maurice Wilkins Centre, University of Otago, Dunedin, New Zealand., Grusch M; Center for Cancer Research and Comprehensive Cancer Center, Medical University of Vienna, Austria.
Jazyk: angličtina
Zdroj: Molecular oncology [Mol Oncol] 2024 Apr; Vol. 18 (4), pp. 815-831. Date of Electronic Publication: 2023 Jan 25.
DOI: 10.1002/1878-0261.13367
Abstrakt: Pleural mesothelioma (PM) is characterized by rapid growth, local invasion, and limited therapeutic options. The multifunctional oncoprotein Y-box-binding protein-1 (YB-1) is frequently overexpressed in cancer and its inhibition reduces aggressive behavior in multiple tumor types. Here, we investigated the effects of YB-1 on target gene regulation and PM cell behavior. Whereas siRNA-mediated YB-1 knockdown reduced cell motility, YB-1 overexpression resulted in scattering, increased migration, and intravasation in vitro. Furthermore, YB-1 stimulated PM cell spreading in zebrafish. Combined knockdown and inducible overexpression of YB-1 allowed bidirectional control and rescue of cell migration, the pattern of which was closely followed by the mRNA and protein levels of EGFR and the protein level of snail, whereas the mRNA levels of MMP1, EPHA5, and PARK2 showed partial regulation by YB-1. Finally, we identified snail as a critical regulator of YB-1-mediated cell motility in PM. This study provides insights into the mechanism underlying the aggressive nature of PM and highlights the important role of YB-1 in this cancer. In this context, we found that YB-1 closely regulates EGFR and snail, and, moreover, that YB-1-induced cell migration depends on snail.
(© 2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf ofFederation of European Biochemical Societies.)
Databáze: MEDLINE
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