Effect Of Ste20-like Kinase On Migration And Invasion Of Glioma

Objective1.To confirm whether SLK was expressed in gliomas and the correlation with E-cadherin,which was the marker of epithelial cells.Besides,intended to explore the expression of SLK significantly related to the development of gliomas.2.To explore the biological significance of endogenous SLK in the development and progression of glioma cells.Methods1.At the tissue level,6 specimens of fresh gliomas with different pathological grades were detected by Western blot;The percentage of the SLK positive cells in each specimen was calculated in the 104 samples using immunohistochemical evaluation.Kaplan-meier method was used to analyze the correlation between SLK and the clinical prognosis of glioma patients.All statistical analyses were performed with SPSS 13.0 software(SPSS,Inc,Chicago,IL).2.The expression level of SLK and E-cadherin were investigated by western blot.we used the dysfunction of SLK in human glioma cell models with RNA interference(RNAi)to silence SLK gene expression.Both transwell migration assay and monolayer wound-healing assays were used to analyze the effect of SLK expression on the aggressiveness of glioma cells.Results1.The expression level of SLK,at both protein and mRNA levels,was markedly higher in glioma tissues compared with normal brain tissues,increased with the malignant degree.and the expression level of SLK was strongly related to the clinicopathologic grades(P=0.031).However,no significant correlation was observed between SLK expression and patient's age,gender and location of the tumor in 104 glioma cases,and SLK was associated with surgical resection range,tumor size,and necrosis.By Spearman analysis,we noticed that SLK expression was negatively correlated with E-cadherin expression,which was the marker of epithelial cells(?=0.687;P<0.005).The Kaplan–Meier survival curves revealed that poor survival was associated with high SLK expression(P<0.005).2.Silencing SLK drastically repressed E-cadherin expression companied with a down-regulation of vimentin on mRNA and protein level in glioma cells.Both transwell migration assay and monolayer wound-healing assays showed that depletion of endogenous SLK drastically inhibited the glioma invasionConclusions1.SLK expression strongly correlated with the clinicopathologic grade of glioma.The inhibition of SLK by RNA interference significantly suppressed the invasive ability of glioma,and on protein level,knockdown of SLK leaded to an up-regulation of E-cadherin and a down-regulation of Vimentin in glioma cells.It suggests that SLK may play key roles in the mechanisms of invasion and development of human gliomas.2.Kaplane-Meier analysis revealed that poor survival was associated with high SLK expression,and indicated that prognostic significance of SLK expression in glioma.3.We silenced the SLK expression in glioma cells by siRNA techniques and demonstrated that knock-down of SLK markedly reduced the ability of glioma invasion.These observations indicated that SLK may be a novel therapeutic target for glioma.