Glucose transporter 3 performs a critical role in mTOR-mediated oncogenic glycolysis and tumorigenesis

Abstract

The present study aimed to examine the relationship between mammalian target of rapamycin (mTOR) and glucose transporter 3 (Glut3) in the process of mTOR-mediated oncogenic glycolysis and tumorigenesis. Western blot analysis and quantitative polymerase chain reaction were used to compare the expression of Glut3 in mouse embryonic fibroblasts (MEFs) null for tuberous sclerosis complex 2 (Tsc2−/−) and control Tsc2+/+ MEFs. In addition, the glycolytic rate was tested following siRNA-mediated knockdown of Glut3 in Tsc2−/− cells. To determine whether Glut3 depletion affects the ability of cells to form tumors in vivo. Tsc2−/− MEFs infected shGlut3 and shControl were injected into nude mice subcutaneously. The present study demonstrated that the expression of Glut3 is controlled by mTOR in Tsc2−/− cells and that downregulation of Glut3 reduced the glycolytic rate in Tsc2−/− cells. cells. Further studies in nude mice demonstrated that reduced Glut3 expression levels reduced the tumorigenetic effect in cells with hyperactive mTOR complex 1 (mTORC1). The present study indicates for the first time that Glut3 is a downstream target of mTORC1 and that Glut3 is critical in mTORC1-associated tumorigenesis. Therefore, Glut3 is a potential target for the treatment of diseases associated with dysregulated mTORC1 signaling.