Rsk2 inhibition induces an aneuploid post-mitotic arrest of cell cycle progression in osteosarcoma cells
Abstract Osteosarcoma is the most common primary bone tumor, which is associated with a high mortality rate. The c-Fos transgenic mouse model has been described to spontaneously develop osteosarcoma, and the ribosomal S6 kinase 2 (Rsk2) was found to be essential for c-Fos-induced osteosarcoma format...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-07-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-025-02596-5 |
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| author | Armelle Carreau Christina Baldauf Lena Warlich Magdalena Weingartner Laura Brylka Michael Amling Thorsten Schinke Julia Luther |
| author_facet | Armelle Carreau Christina Baldauf Lena Warlich Magdalena Weingartner Laura Brylka Michael Amling Thorsten Schinke Julia Luther |
| author_sort | Armelle Carreau |
| collection | DOAJ |
| description | Abstract Osteosarcoma is the most common primary bone tumor, which is associated with a high mortality rate. The c-Fos transgenic mouse model has been described to spontaneously develop osteosarcoma, and the ribosomal S6 kinase 2 (Rsk2) was found to be essential for c-Fos-induced osteosarcoma formation in mice. By isolating and characterizing osteosarcoma cell lines from FosTg and FosTg;Rsk2 −/y mice, we observed that Rsk2 deficiency impairs the growth advantage of FosTg cells. This can be explained by the aberrant number of nuclei due to impaired cytokinesis, inducing mitotic catastrophe. We therefore tested a pharmacological Rsk inhibitor (BI-D1870) for its ability to inhibit the proliferation of osteosarcoma cells and found that the effects observed by genetic Rsk2 inactivation were mimicked. BI-D1870 administration to FosTg cell lines led to reduced expression of Aurora kinase B. Therefore, the influence of a pharmacological Aurora kinase B inhibitor (Hesperadin) was tested. Similar to BI-D1870, Hesperadin caused impaired cytokinesis, resulting in the accumulation of polynuclear cells. This effect was also observed for two human osteosarcoma cell lines, U2OS and SaOS-2. Based on our findings, Rsk2 and/or Aurora kinase B can serve as potential targets for the design of new osteosarcoma therapies. |
| format | Article |
| id | doaj-art-dea3de80f1714ac5b954a96e4cd91a17 |
| institution | Kabale University |
| issn | 2058-7716 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj-art-dea3de80f1714ac5b954a96e4cd91a172025-08-20T03:45:45ZengNature Publishing GroupCell Death Discovery2058-77162025-07-0111111210.1038/s41420-025-02596-5Rsk2 inhibition induces an aneuploid post-mitotic arrest of cell cycle progression in osteosarcoma cellsArmelle Carreau0Christina Baldauf1Lena Warlich2Magdalena Weingartner3Laura Brylka4Michael Amling5Thorsten Schinke6Julia Luther7Department of Osteology and Biomechanics, University Medical Center Hamburg-EppendorfDepartment of Osteology and Biomechanics, University Medical Center Hamburg-EppendorfDepartment of Osteology and Biomechanics, University Medical Center Hamburg-EppendorfInstitute of Plant Sciences and Microbiology, University of HamburgDepartment of Osteology and Biomechanics, University Medical Center Hamburg-EppendorfDepartment of Osteology and Biomechanics, University Medical Center Hamburg-EppendorfDepartment of Osteology and Biomechanics, University Medical Center Hamburg-EppendorfDepartment of Osteology and Biomechanics, University Medical Center Hamburg-EppendorfAbstract Osteosarcoma is the most common primary bone tumor, which is associated with a high mortality rate. The c-Fos transgenic mouse model has been described to spontaneously develop osteosarcoma, and the ribosomal S6 kinase 2 (Rsk2) was found to be essential for c-Fos-induced osteosarcoma formation in mice. By isolating and characterizing osteosarcoma cell lines from FosTg and FosTg;Rsk2 −/y mice, we observed that Rsk2 deficiency impairs the growth advantage of FosTg cells. This can be explained by the aberrant number of nuclei due to impaired cytokinesis, inducing mitotic catastrophe. We therefore tested a pharmacological Rsk inhibitor (BI-D1870) for its ability to inhibit the proliferation of osteosarcoma cells and found that the effects observed by genetic Rsk2 inactivation were mimicked. BI-D1870 administration to FosTg cell lines led to reduced expression of Aurora kinase B. Therefore, the influence of a pharmacological Aurora kinase B inhibitor (Hesperadin) was tested. Similar to BI-D1870, Hesperadin caused impaired cytokinesis, resulting in the accumulation of polynuclear cells. This effect was also observed for two human osteosarcoma cell lines, U2OS and SaOS-2. Based on our findings, Rsk2 and/or Aurora kinase B can serve as potential targets for the design of new osteosarcoma therapies.https://doi.org/10.1038/s41420-025-02596-5 |
| spellingShingle | Armelle Carreau Christina Baldauf Lena Warlich Magdalena Weingartner Laura Brylka Michael Amling Thorsten Schinke Julia Luther Rsk2 inhibition induces an aneuploid post-mitotic arrest of cell cycle progression in osteosarcoma cells Cell Death Discovery |
| title | Rsk2 inhibition induces an aneuploid post-mitotic arrest of cell cycle progression in osteosarcoma cells |
| title_full | Rsk2 inhibition induces an aneuploid post-mitotic arrest of cell cycle progression in osteosarcoma cells |
| title_fullStr | Rsk2 inhibition induces an aneuploid post-mitotic arrest of cell cycle progression in osteosarcoma cells |
| title_full_unstemmed | Rsk2 inhibition induces an aneuploid post-mitotic arrest of cell cycle progression in osteosarcoma cells |
| title_short | Rsk2 inhibition induces an aneuploid post-mitotic arrest of cell cycle progression in osteosarcoma cells |
| title_sort | rsk2 inhibition induces an aneuploid post mitotic arrest of cell cycle progression in osteosarcoma cells |
| url | https://doi.org/10.1038/s41420-025-02596-5 |
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