Related Experiment Video

Updated: Mar 21, 2026

Protocol for the Differentiation of Human Induced Pluripotent Stem Cells into Mixed Cultures of Neurons and Glia for Neurotoxicity Testing
09:02

Protocol for the Differentiation of Human Induced Pluripotent Stem Cells into Mixed Cultures of Neurons and Glia for Neurotoxicity Testing

Published on: June 9, 2017

24.6K

Nrf2-driven TERT regulates pentose phosphate pathway in glioblastoma

F Ahmad1, D Dixit1, V Sharma2

  • 1National Brain Research Centre, Department of Molecular and Cellular Neuroscience Division, Manesar, Gurgaon, Haryana 122051, India.

Cell Death & Disease
|May 6, 2016
PubMed

Insights

This study reveals telomerase regulates cellular metabolism in glioma. Inhibiting human Telomerase reverse transcriptase (hTERT) impacts the pentose phosphate pathway and glycogen, affecting tumor growth.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Metabolism

Background:

  • Glioma progression involves telomerase activation and altered metabolism.
  • The interplay between telomerase and metabolic pathways in glioma remains underexplored.

Purpose of the Study:

  • To investigate the connection between telomerase (hTERT) and metabolic dysregulation in glioma.
  • To elucidate the role of hTERT in regulating key metabolic pathways and cellular responses.

Main Methods:

  • Pharmacological inhibition of hTERT using Costunolide.
  • siRNA-mediated knockdown and dominant-negative hTERT (DN-hTERT) expression.
  • Analysis of reactive oxygen species (ROS), p53, Nrf2, pentose phosphate pathway (PPP) enzymes (G6PD, TKT), and glycogen metabolism.
  • In vivo studies using a xenograft glioma mouse model.
  • Analysis of glioblastoma multiforme (GBM) patient tumors with TERT promoter mutations.

Main Results:

  • Costunolide induced glioma cell apoptosis via ROS-dependent mechanisms, increasing p53 and abrogating telomerase activity.
  • hTERT inhibition decreased Nrf2 levels and key PPP enzymes (G6PD, TKT), leading to increased glycogen accumulation.
  • An Nrf2-TERT feedback loop was identified, influencing oxidative defense.
  • Costunolide reduced tumor burden in vivo, with decreased TKT activity and increased glycogen/senescence in tumors.
  • GBM tumors with TERT mutations showed elevated Nrf2/TKT and reduced glycogen.

Conclusions:

  • Telomerase (hTERT) plays a novel role in regulating the pentose phosphate pathway and glycogen accumulation in glioma.
  • The Nrf2-TERT axis is crucial for maintaining oxidative defense in glioma cells.
  • Targeting hTERT and its associated metabolic pathways presents a potential therapeutic strategy for glioma.

Related Concept Videos

Other Glycolytic Pathways01:24

Other Glycolytic Pathways

The pentose phosphate pathway (PPP) operates in parallel with glycolysis, facilitating the metabolism of both pentoses and glucose. This pathway consists of two distinct phases: the oxidative and non-oxidative phases. While it does not directly generate ATP, the intermediates formed during the process can integrate into glycolysis, contributing to cellular energy metabolism when required.Oxidative Phase: NADPH ProductionThe oxidative phase of the pentose phosphate pathway is primarily...
1.1K
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
10.3K
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.9K
NF-kB-dependent Signaling Pathway02:26

NF-kB-dependent Signaling Pathway

2.4K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
5.0K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
9.1K