GOLPH3 promotes glioblastoma cell migration and invasion via the mTOR-YB1 pathway in vitro.

Abstract

The identification of genes involved in carcinogenesis and tumor progression is of great interest, since these genes might be possible as candidates for new tumor targeted therapy strategies. Our previous study shows that Golgi phosphoprotein 3 (GOLPH3) is involved in glioma cell migration and invasion, the critical characteristics of malignant gliomas. In this study, we explored the mechanism of GOLPH3 affecting cell migration and invasion and found that GOLPH3 promotes glioblastoma (GBM) cell migration and invasion via the mammalian target of rapamycin(mTOR)-Y-box binding protein-1 (YB1) pathway in vitro. Both the protein levels of GOLPH3 and YB1 were up-regulated in human glioma tissues and they exhibited direct correlation with each other. In addition, down-regulation of GOLPH3 inhibited glioma cell migration and invasion, while over-expression of GOLPH3 enhanced them. Meanwhile, GOLPH3 down-regulation led to a significant decrease of YB1 level as well as mTOR activity, both required for glioma cell migration and invasion. On the contrary, YB1 level and mTOR activity increased after GOLPH3 over-expression. YB1 down-regulation or mTOR ATP site inhibitor INK128 treatment inhibited cell migration and invasion, similar to the effect of GOLPH3 down-regulation. Furthermore, over-expression of GOLPH3 induced glioma cell migration and invasion was blocked by INK128 and YB1 down-regulation. Taken together, these results show that GOLPH3 promotes glioblastoma cell migration and invasion via the mTOR-YB1pathway, indicating that GOLPH3-mTOR-YB1 pathway might be a new therapeutic target for glioma treatment.