IDH1 mutation activates mTOR signaling pathway, promotes cell proliferation and invasion in glioma cells

Mol Biol Rep. 2022 Oct;49(10):9241-9249. doi: 10.1007/s11033-022-07750-1. Epub 2022 Aug 7.


Background: Glioma is the most common type of brain tumors and isocitrate dehydrogenase (IDH1) gene is the most prominent molecular marker about the disease prognosis, response to therapy and patient survival. There are conflicting data about the effect of IDH1 mutation on glial cell proliferation, invasion and migration characteristics. The effect of IDH1 mutation on mTOR signaling pathway, which has key roles in tumorigenesis process, is limited and previous data is controversial. We aimed to explore the effect of wild type and mutant IDH1 overexpression on glioma cells and investigated the correlation with mTOR signaling pathway associated genes.

Methods and results: U87-MG and A172 cells were transfected with different IDH1 mutant gene overexpressing (R132H, R132L, R132S, R132C) viral vectors. Cell proliferation, cell invasion and migration analysis as well as quantitative PCR analysis with the mutant glioma cell lines were performed. Forty-two patient derived glioma cells were obtained from patients with different glioma subtypes and cancer cells were enriched by culturing cells. Overexpression of both mutant and wild type IDH1 gene promoted the cell proliferation, but only IDH1 mutation increased cell invasion and migration. The expression of IDH1 mutation activated mTOR signaling via upregulation of WNTA, PRKAA2, GSK3B and MTOR genes as well as phosphorylated mTOR protein level.

Conclusions: Our results highlighted IDH1 mutation upregulate mTOR signaling pathway and promote cell proliferation, invasion and migration.

Keywords: Cell invasion; Cell migration; Cell proliferation; Glioma; IDH1; mTOR pathway.

MeSH terms

  • Brain Neoplasms* / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Glioma* / metabolism
  • Humans
  • Isocitrate Dehydrogenase / genetics
  • Isocitrate Dehydrogenase / metabolism
  • Mutation / genetics
  • Signal Transduction / genetics
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism


  • Isocitrate Dehydrogenase
  • IDH1 protein, human
  • MTOR protein, human
  • TOR Serine-Threonine Kinases