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Review
. 2016 Dec 14;4(1):19-24.
doi: 10.1016/j.gendis.2016.11.003. eCollection 2017 Mar.

The role of hypoxia-inducible factors in tumor angiogenesis and cell metabolism

Xiu Lv  1   2 , Jincheng Li  3 , Chuhong Zhang  1 , Tian Hu  1 , Sai Li  1 , Sha He  1 , Hanxing Yan  1 , Yixi Tan  1 , Mingsheng Lei  4 , Meiling Wen  1 , Jianhong Zuo  1   2
Affiliations
Review

The role of hypoxia-inducible factors in tumor angiogenesis and cell metabolism

Xiu Lv et al. Genes Dis. .

Abstract

Hypoxia-inducible factor (HIF) is a main heterodimeric transcription factor that regulates the cellular adaptive response to hypoxia by stimulating the transcription of a series of hypoxia-inducible genes. HIF is frequently upregulated in solid tumors, and the overexpression of HIF can promote tumor progression or aggressiveness by blood vessel architecture and altering cellular metabolism. In this review, we focused on the pivotal role of HIF in tumor angiogenesis and energy metabolism. Furthermore, we also emphasized the possibility of HIF pathway as a potential therapeutic target in cancer.

Keywords: Angiogenesis; HIF; Hypoxia; Metabolism; VHL.

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Figures

Fig. 1
Fig. 1
Effects of hypoxia on tumor cells metabolism. Under hypoxic conditions, glucose is converted to lactate rather than to metabolized acetyl-CoA to enter TCA cycle and OXPHOS in the mitochondria. A number of the effects of hypoxia on cancer metabolism are explained by the HIF-1α-mediated activation of glycolytic enzymes and LDHA and inhibition of PDH, and this phenomenon that tumor cells shift from oxidative phosphorylation to glycolysis, even under normoxia, was termed Warburg effect. As a consequence, tumor cells are protected from ROS damage generated from ETC in hypoxic condition.
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