ReferenceID 3460
Nrf2-driven TERT regulates pentose phosphate pathway in glioblastoma
Cell Death Dis
Given the involvement of telomerase activation and dysregulated metabolism in glioma progression, the connection between these two critical players was investigated. Pharmacological inhibition of human Telomerase reverse
Relationship Network
Interactive first-hop connections across herbs, ingredients, formulas, targets, diseases, symptoms, syndromes, evidence, and monographs.
Click a node to open it in a new tab
Ingredient: 1Reference: 1Links: 1
Arranging relationship network...
Record Fields
Scalar fields from the final reference record.
- Reference Id
- 3460
- Evidence Id
- 20050
- Core Evidence Id
- 20050
- Source Reference Id
- 227
- Herb2 Reference Id
- HBREF000430
- Subject Paper Key
- HBIN021599_27148686
- Pubmed Id
- 27148686
- Doi
- 10.1038/cddis.2016.117
- Paper Title
- Nrf2-driven TERT regulates pentose phosphate pathway in glioblastoma
- Paper Abstract
- Given the involvement of telomerase activation and dysregulated metabolism in glioma progression, the connection between these two critical players was investigated. Pharmacological inhibition of human Telomerase reverse transcriptase (hTERT) by Costunolide induced glioma cell apoptosis in a reactive oxygen species (ROS)-dependent manner. Costunolide induced an ROS-dependent increase in p53 abrogated telomerase activity. Costunolide decreased Nrf2 level; and ectopic Nrf2 expression decreased Costunolide-induced ROS generation. While TERT knock-down abrogated Nrf2 levels, overexpression of Nrf2 increased TERT expression. Inhibition of hTERT either by Costunolide, or by siRNA or dominant-negative hTERT (DN-hTERT) abrogated (i) expression of Glucose-6-phosphate dehydrogenase (G6PD) and Transketolase (TKT) - two major nodes in the pentose phosphate (PPP) pathway; and (ii) phosphorylation of glycogen synthase (GS). hTERT knock-down decreased TKT activity and increased glycogen accumulation. Interestingly, siRNA-mediated knock-down of TKT elevated glycogen accumulation. Coherent with the in vitro findings, Costunolide reduced tumor burden in heterotypic xenograft glioma mouse model. Costunolide-treated tumors exhibited diminished TKT activity, heightened glycogen accumulation, and increased senescence. Importantly, glioblastoma multiforme (GBM) patient tumors bearing TERT promoter mutations (C228T and C250T) known to be associated with increased telomerase activity; exhibited elevated Nrf2 and TKT expression and decreased glycogen accumulation. Taken together, our findings highlight the previously unknown (i) role of telomerase in the regulation of PPP and glycogen accumulation and (ii) the involvement of Nrf2-TERT loop in maintaining oxidative defense responses in glioma cells.
- Journal
- Cell Death Dis
- Publish Year
- 2016
- Experiment Subject
- glioma cell
- Experiment Type
- Cell Experiment
- Phenotype Related
- Paper Title Cn
- Paper Title En
- Nrf2-driven TERT regulates pentose phosphate pathway in glioblastoma
- Bilingual Status
- semi_complete