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

• Published in: Cells (Basel, Switzerland) Switzerland), 2019-08, Vol.8 (8), p.808
• Main Authors: Celik-Selvi, Burcu Emine, Stütz, Astrid, Mayer, Christoph-Erik, Salhi, Jihen, Siegwart, Gerald, Sutterlüty, Hedwig
• Format: Article
• Language: English
• Subjects: Adenoviruses; Antibodies; Brain cancer; Brain Neoplasms - metabolism; Brain tumors; Cancer; Carcinogenesis - metabolism; Cell Line, Tumor; Cell migration; Cell Proliferation; Cloning; Ectopic expression; FGF-mediated signaling; Fibroblast growth factors; Glioblastoma; Glioblastoma - metabolism; Growth factors; Humans; Infections; Intracellular Signaling Peptides and Proteins - physiology; Kinases; MAP kinase; Medical prognosis; Nerve Tissue Proteins - physiology; Nervous system; Neuroblastoma; Protein-tyrosine kinase receptors; Proteins; RNA, Small Interfering - metabolism; Signal Transduction; Sprouty proteins; Tumor cell lines; tumor promoter; tumor suppressor; Tumor suppressor genes; Tumors; Viruses
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells8080808

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.