The rise of viperin: the emerging role of viperin in cancer progression
Alyssa G. Weinstein, … , Inês Godet, Daniele M. Gilkes
Alyssa G. Weinstein, … , Inês Godet, Daniele M. Gilkes
Published December 15, 2022
Citation Information: J Clin Invest. 2022;132(24):e165907. https://doi.org/10.1172/JCI165907.
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Commentary

The rise of viperin: the emerging role of viperin in cancer progression

Abstract

Viperin, an IFN-regulated gene product, is known to inhibit fatty acid β-oxidation in the mitochondria, which enhances glycolysis and lipogenesis during viral infections. Yet, its role in altering the phenotype of cancer cells has not been established. In this issue of the JCI, Choi, Kim, and co-authors report on a role of viperin in regulating metabolic alterations in cancer cells. The authors showed a correlation between clinical outcomes and viperin expression levels in multiple cancer tissues and proposed that viperin expression was upregulated in the tumor microenvironment via the JAK/STAT and PI3K/AKT/mTOR/HIF-1α pathways. Functionally, viperin increased lipogenesis and glycolysis in cancer cells by inhibiting fatty acid β-oxidation. Viperin expression also enhanced cancer stem cell properties, ultimately promoting tumor initiation in murine models. This study proposes a protumorigenic role for viperin and identifies HIF-1α as a transcription factor that increases viperin expression under serum starvation and hypoxia.

Authors

Alyssa G. Weinstein, Inês Godet, Daniele M. Gilkes

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Figure 1

Viperin promotes cancer cell proliferation in low-oxygen and/or nutrient-deprived conditions in the TME.

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Viperin promotes cancer cell proliferation in low-oxygen and/or nutrient...
Choi, Kim, and colleagues report that cancer cells expressing high levels of viperin have increased levels of glycolysis and lipogenesis in the absence of oxygen and nutrients. This metabolic reprogramming occurs via two pathways: (a) the phosphorylated AKT/mTOR (p-AKT/mTOR) pathway, which is stimulated by a lack of oxygen and nutrients and activates downstream transcription factors, such as HIF1-α, to increase the transcription of viperin; and (b) the JAK/STAT pathway, which is activated by increased production of IFNs, where STAT binds directly to the DNA to increase viperin transcription. Viperin inhibits fatty acid β-oxidation, thus increasing glycolysis and lipogenesis in the presence of glucose. Additionally, viperin expression coincides with the enrichment of CSC properties (7).