TY - JOUR AB - Glioblastoma (GBM) is the most common type of brain cancer and has the highest mortality. Dysregulated expression of wild‑type isocitrate dehydrogenase 1 (IDH1) has been demonstrated to promote the progression of primary GBM without accumulating D‑2‑hydroxyglutarate, which differs from IDH1 mutation‑related mechanisms of tumorigenesis. Previous studies have revealed several roles of wild‑type IDH1 in primary GBM, involving proliferation and apoptosis. However, the function of IDH1 in cell migration has not been investigated. In the current study, the results of bioinformatics analysis revealed that IDH1 expression was significantly upregulated in patients with primary GBM. Wound healing and Transwell assays demonstrated that IDH1 overexpression promoted cell migration in primary GBM cells and that IDH1 knockdown hindered this process. Furthermore, α‑ketoglutarate (α‑KG), which is the main product of IDH1‑catalyzed reactions, was significantly decreased by IDH1 knockdown and upregulated by IDH1 overexpression. α‑KG treatment significantly increased the migration of primary GBM cells. Additionally, RNA sequence analysis of patients with primary GBM reported significant alterations in the expression of phosphoinositide 3‑kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway‑regulated genes, including Myc, Snail family transcriptional repressor 2 and Twist‑related protein 1, which are primarily cell migration regulatory factors. Western blotting revealed that the overexpression or knockdown of IDH1 promoted or inhibited the PI3K/AKT/mTOR pathway, respectively. α‑KG treatment of primary GBM cells also promoted the PI3K/AKT/mTOR pathway. Furthermore, IDH1‑overexpressing and α‑KG‑treated U87 cells were incubated with rapamycin, an mTOR‑specific inhibitor, and the results revealed that rapamycin treatment reversed the increased cell migration caused by IDH1 overexpression and α‑KG treatment. The results indicated that IDH1 regulated the migration of primary GBM cells by altering α‑KG levels and that the function of the IDH1/α‑KG axis may rely on PI3K/AKT/mTOR pathway regulation. AD - Anhui Provincial Key Laboratory of the Conservation and Exploitation of Biological Resources, College of Life Sciences, Anhui Normal University, Wuhu, Anhui 241000, P.R. China Department of Inspection, Wuhu Center for Disease Control and Prevention, Wuhu, Anhui 241000, P.R. China AU - Shen,Xiaopeng AU - Wu,Shen AU - Zhang,Jingyi AU - Li,Meng AU - Xu,Feng AU - Wang,Ao AU - Lei,Yang AU - Zhu,Guoping DA - 2020/09/01 DO - 10.3892/mmr.2020.11250 EP - 1957 IS - 3 JO - Mol Med Rep KW - primary glioblastoma isocitrate dehydrogenase 1 α‑ketoglutarate cell migration phosphoinositide 3‑kiase/protein kinase B/mammalian target of rapamycin pathway PY - 2020 SN - 1791-2997 1791-3004 SP - 1949 ST - Wild‑type IDH1 affects cell migration by modulating the PI3K/AKT/mTOR pathway in primary glioblastoma cells T2 - Molecular Medicine Reports TI - Wild‑type IDH1 affects cell migration by modulating the PI3K/AKT/mTOR pathway in primary glioblastoma cells UR - https://doi.org/10.3892/mmr.2020.11250 VL - 22 ER -