Sprouty3 and Sprouty4, Two Members of a Family Known to Inhibit FGF-Mediated Signaling, Exert Opposing Roles on Proliferation and Migration of Glioblastoma-Derived Cells
Dysregulation of receptor tyrosine kinase-induced pathways is a critical step driving the oncogenic potential of brain cancer. In this study, we investigated the role of two members of the Sprouty (Spry) family in brain cancer-derived cell lines. Using immunoblot analyses we found essential differen...
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| Format: | Article |
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MDPI AG
2019-08-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/8/8/808 |
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| author | Burcu Emine Celik-Selvi Astrid Stütz Christoph-Erik Mayer Jihen Salhi Gerald Siegwart Hedwig Sutterlüty |
| author_facet | Burcu Emine Celik-Selvi Astrid Stütz Christoph-Erik Mayer Jihen Salhi Gerald Siegwart Hedwig Sutterlüty |
| author_sort | Burcu Emine Celik-Selvi |
| collection | DOAJ |
| description | Dysregulation of receptor tyrosine kinase-induced pathways is a critical step driving the oncogenic potential of brain cancer. In this study, we investigated the role of two members of the Sprouty (Spry) family in brain cancer-derived cell lines. Using immunoblot analyses we found essential differences in the pattern of endogenous Spry3 and Spry4 expression. While Spry4 expression was mitogen-dependent and repressed in a number of cells from higher malignant brain cancers, Spry3 levels neither fluctuated in response to serum withdrawal nor were repressed in glioblastoma (GBM)-derived cell lines. In accordance to the well-known inhibitory role of Spry proteins in fibroblast growth factor (FGF)-mediated signaling, both Spry proteins were able to interfere with FGF-induced activation of the MAPK pathway although to a different extent. In response to serum solely, Spry4 exerts its role as a negative regulator of MAPK activation. Ectopic expression of Spry4 inhibited proliferation and migration of GBM-originated cells, positioning it as a tumor suppressor in brain cancer. In contrast, elevated Spry3 levels accelerated both proliferation and migration of these cell lines, while repression of Spry3 levels using shRNA caused a significant diminished growth and migration velocity rate of a GBM-derived cell line. This argues for a tumor-promoting function of Spry3 in GBMs. Based on these data we conclude that Spry3 and Spry4 fulfill different if not opposing roles within the cancerogenesis of brain malignancies. |
| first_indexed | 2024-03-12T08:03:28Z |
| format | Article |
| id | doaj.art-f3da0b46cbfb4f79ad57fa11a4993f23 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T08:03:28Z |
| publishDate | 2019-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-f3da0b46cbfb4f79ad57fa11a4993f232023-09-02T19:46:07ZengMDPI AGCells2073-44092019-08-018880810.3390/cells8080808cells8080808Sprouty3 and Sprouty4, Two Members of a Family Known to Inhibit FGF-Mediated Signaling, Exert Opposing Roles on Proliferation and Migration of Glioblastoma-Derived CellsBurcu Emine Celik-Selvi0Astrid Stütz1Christoph-Erik Mayer2Jihen Salhi3Gerald Siegwart4Hedwig Sutterlüty5Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, A-1090 Vienna, AustriaInstitute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, A-1090 Vienna, AustriaInstitute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, A-1090 Vienna, AustriaInstitute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, A-1090 Vienna, AustriaInstitute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, A-1090 Vienna, AustriaInstitute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, A-1090 Vienna, AustriaDysregulation of receptor tyrosine kinase-induced pathways is a critical step driving the oncogenic potential of brain cancer. In this study, we investigated the role of two members of the Sprouty (Spry) family in brain cancer-derived cell lines. Using immunoblot analyses we found essential differences in the pattern of endogenous Spry3 and Spry4 expression. While Spry4 expression was mitogen-dependent and repressed in a number of cells from higher malignant brain cancers, Spry3 levels neither fluctuated in response to serum withdrawal nor were repressed in glioblastoma (GBM)-derived cell lines. In accordance to the well-known inhibitory role of Spry proteins in fibroblast growth factor (FGF)-mediated signaling, both Spry proteins were able to interfere with FGF-induced activation of the MAPK pathway although to a different extent. In response to serum solely, Spry4 exerts its role as a negative regulator of MAPK activation. Ectopic expression of Spry4 inhibited proliferation and migration of GBM-originated cells, positioning it as a tumor suppressor in brain cancer. In contrast, elevated Spry3 levels accelerated both proliferation and migration of these cell lines, while repression of Spry3 levels using shRNA caused a significant diminished growth and migration velocity rate of a GBM-derived cell line. This argues for a tumor-promoting function of Spry3 in GBMs. Based on these data we conclude that Spry3 and Spry4 fulfill different if not opposing roles within the cancerogenesis of brain malignancies.https://www.mdpi.com/2073-4409/8/8/808Sprouty proteinsbrain cancerFGF-mediated signalingtumor suppressortumor promoter |
| spellingShingle | Burcu Emine Celik-Selvi Astrid Stütz Christoph-Erik Mayer Jihen Salhi Gerald Siegwart Hedwig Sutterlüty Sprouty3 and Sprouty4, Two Members of a Family Known to Inhibit FGF-Mediated Signaling, Exert Opposing Roles on Proliferation and Migration of Glioblastoma-Derived Cells Cells Sprouty proteins brain cancer FGF-mediated signaling tumor suppressor tumor promoter |
| title | Sprouty3 and Sprouty4, Two Members of a Family Known to Inhibit FGF-Mediated Signaling, Exert Opposing Roles on Proliferation and Migration of Glioblastoma-Derived Cells |
| title_full | Sprouty3 and Sprouty4, Two Members of a Family Known to Inhibit FGF-Mediated Signaling, Exert Opposing Roles on Proliferation and Migration of Glioblastoma-Derived Cells |
| title_fullStr | Sprouty3 and Sprouty4, Two Members of a Family Known to Inhibit FGF-Mediated Signaling, Exert Opposing Roles on Proliferation and Migration of Glioblastoma-Derived Cells |
| title_full_unstemmed | Sprouty3 and Sprouty4, Two Members of a Family Known to Inhibit FGF-Mediated Signaling, Exert Opposing Roles on Proliferation and Migration of Glioblastoma-Derived Cells |
| title_short | Sprouty3 and Sprouty4, Two Members of a Family Known to Inhibit FGF-Mediated Signaling, Exert Opposing Roles on Proliferation and Migration of Glioblastoma-Derived Cells |
| title_sort | sprouty3 and sprouty4 two members of a family known to inhibit fgf mediated signaling exert opposing roles on proliferation and migration of glioblastoma derived cells |
| topic | Sprouty proteins brain cancer FGF-mediated signaling tumor suppressor tumor promoter |
| url | https://www.mdpi.com/2073-4409/8/8/808 |
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