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GPT2 Is Induced by Hypoxia-Inducible Factor (HIF)-2 and Promotes Glioblastoma Growth

Authors :
Bo Zhang
Yan Chen
Lei Bao
Weibo Luo
Source :
Cells; Volume 11; Issue 16; Pages: 2597
Publication Year :
2022

Abstract

Hypoxia-inducible factor (HIF) directly activates the transcription of metabolic enzymes in response to hypoxia to reprogram cellular metabolism required for tumor cell proliferation. Through analyzing glutamate-linked aminotransferases, we here identified glutamate pyruvate transaminase 2 (GPT2) as a direct HIF-2 target gene in human glioblastoma (GBM). Hypoxia upregulated GPT2 mRNA and protein levels in GBM cells, which required HIF-2 but not HIF-1. HIF-2 directly bound to the hypoxia response element of the human GPT2 gene, leading to its transcription in hypoxic GBM cells. GPT2 located at the nucleus and mitochondria and reduced α-ketoglutarate levels in GBM cells. Genetic or pharmacological inhibition of GPT2 decreased GBM cell growth and migration under normoxia and hypoxia. Knockout of GPT2 inhibited GBM tumor growth in mice. Collectively, these findings uncover a hypoxia-inducible aminotransferase GPT2 required for GBM progression.

Details

ISSN :
20734409
Volume :
11
Issue :
16
Database :
OpenAIRE
Journal :
Cells
Accession number :
edsair.doi.dedup.....c5fb4fe4ea048696e90b23ef049d26f0