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
Burcu Emine Celik-SelviHedwig Sutterlüty-Fall

Abstract

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 signific...Continue Reading

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Citations

Mar 17, 2020·Expert Opinion on Therapeutic Targets·Ana Jimenez-PascualJustin D Lathia
Oct 22, 2020·Cancers·Maria Francesca Santolla, Marcello Maggiolini
Aug 8, 2021·Cancers·Phuong DoanMeenakshisundaram Kandhavelu

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Methods Mentioned

BETA
Infection
PCR
Fluorescence
FCS

Software Mentioned

GraphPad Prism
ImageJ
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