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

Zhang, Bo; Chen, Yan; Bao, Lei; Luo, Weibo

doi:10.3390/cells11162597

Open AccessArticle

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

by

Bo Zhang

^1,†,

Yan Chen

^1,†,

Lei Bao

¹ and

Weibo Luo

^1,2,*

¹

Department of Pathology, UT Southwestern Medical Center, Dallas, TX 75390, USA

²

Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX 75390, USA

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Cells 2022, 11(16), 2597; https://doi.org/10.3390/cells11162597

Submission received: 10 July 2022 / Revised: 12 August 2022 / Accepted: 17 August 2022 / Published: 20 August 2022

(This article belongs to the Special Issue Hypoxia Signaling and Hormonal Signaling in Cancer Progression)

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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.

Keywords: hypoxia; hypoxia-inducible factor; GPT2; glioblastoma; tumorigenesis

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MDPI and ACS Style

Zhang, B.; Chen, Y.; Bao, L.; Luo, W. GPT2 Is Induced by Hypoxia-Inducible Factor (HIF)-2 and Promotes Glioblastoma Growth. Cells 2022, 11, 2597. https://doi.org/10.3390/cells11162597

AMA Style

Zhang B, Chen Y, Bao L, Luo W. GPT2 Is Induced by Hypoxia-Inducible Factor (HIF)-2 and Promotes Glioblastoma Growth. Cells. 2022; 11(16):2597. https://doi.org/10.3390/cells11162597

Chicago/Turabian Style

Zhang, Bo, Yan Chen, Lei Bao, and Weibo Luo. 2022. "GPT2 Is Induced by Hypoxia-Inducible Factor (HIF)-2 and Promotes Glioblastoma Growth" Cells 11, no. 16: 2597. https://doi.org/10.3390/cells11162597

APA Style

Zhang, B., Chen, Y., Bao, L., & Luo, W. (2022). GPT2 Is Induced by Hypoxia-Inducible Factor (HIF)-2 and Promotes Glioblastoma Growth. Cells, 11(16), 2597. https://doi.org/10.3390/cells11162597

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

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

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