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Mutant IDH1 inhibits PI3K/Akt signaling in human glioma

Peter Birner1, Stefan Pusch, Christo Christov

  • 1Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany; Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria.

Cancer
|April 29, 2014
PubMed
Abstract

Insights

Mutant isocitrate dehydrogenase 1 (IDH1) inhibits phosphoinositide 3-kinase (PI3K)/Akt signaling in gliomas. This study found an inverse correlation between mutant IDH1 and active PI3K/Akt signaling markers.

Area of Science:

  • Neuro-oncology
  • Molecular Biology
  • Cancer Signaling Pathways

Background:

  • Isocitrate dehydrogenase 1 (IDH1) is crucial in glioma development.
  • The role of IDH1 in signaling pathways remains unclear.
  • Genes regulated by phosphoinositide 3-kinase (PI3K)/Akt signaling are downregulated in IDH-mutated gliomas.

Purpose of the Study:

  • To investigate a potential link between IDH1 and PI3K/Akt signaling.
  • To determine if mutant IDH1 affects PI3K/Akt pathway activity.

Main Methods:

  • Examined mutant IDH1 and PI3K/Akt signaling markers (phosphorylated Akt, podoplanin) in 354 glioma patients.
  • Conducted in vitro experiments to confirm functional relationships.

Main Results:

  • An inverse correlation was observed between mutant IDH1 and active PI3K/Akt signaling markers.
  • In vitro, mutant IDH1 expression inhibited Akt phosphorylation in a 2-hydroxyglutarate-dependent manner.

Conclusions:

  • Mutant IDH1 appears to inhibit PI3K/Akt signaling.
  • Evidence from patient tumors and in vitro studies supports this inhibitory role.
Keywords:
AktIDH1PDPNastrocytomaglioblastomaglioma

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