Sprouty 4 suppresses glioblastoma invasion by inhibiting ERK phosphorylation and ETS-1-induced matrix metalloproteinase-9.

Abstract

Glioblastoma multiforme (GBM) is the most malignant glioma with highly aggressive behavior and the worst prognosis. Many efforts have been made to develop new drugs and improve the patient's survival, but the effects are not satisfactory. Here we aimed to evaluate the clinical significance and tumor-repressive function of Sprouty4 (SPRY4) in GBM. In our study, we detected the expression of SPRY4 in 109 GBM patients and 12 pairs of GBM tissues and the corresponding adjacent tissues. χ2 test was applied to analyze the association between SPRY4 expression and the clinicopathological factors. The prognostic significances were evaluated with univariate and multivariate analyses, which were carried out by the Kaplan-Meier method and the Cox-regression proportional hazards model, respectively. With in-vitro experiments, we investigated the tumor-suppressing function of SPRY4 in GBM invasion and investigated the underlying mechanism. SPRY4 mRNAs in GBMs were significantly lower than those in adjacent brain tissues. We demonstrated that SPRY4 expression could predict the favorable prognosis of GBM, and SPRY4 was an independent favorable prognostic factor of GBM. SPRY4 repressed GBM invasion via inhibiting ERK phosphorylation; therefore, suppressing ETS-1-induced MMP9 expression. SPRY4 was an independent favorable prognostic factor of GBM, and it could suppress GBM invasion by ERK-ETS-MMP9 axis. Our results indicated that SPRY4 may be a promising drug target of GBM and SPRY4 detection could stratify patients with low SPRY4 expression who may benefit from anti-FGFR therapy.