The interferon-inducible protein viperin controls cancer metabolic reprogramming to enhance cancer progression

Kyung Mi Choi, Jeong Jin Kim, Jihye Yoo, Ku Sul Kim, Youngeun Gu, John Eom, Haengdueng Jeong, Kyungeun Kim, Ki Taek Nam, Young Soo Park, Joon Yong Chung, Jun Young Seo

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1 Citation (Scopus)


Metabolic reprogramming is an important cancer hallmark. However, the mechanisms driving metabolic phenotypes of cancer cells are unclear. Here, we show that the interferon-inducible (IFN-inducible) protein viperin drove metabolic alteration in cancer cells. Viperin expression was observed in various types of cancer and was inversely correlated with the survival rates of patients with gastric, lung, breast, renal, pancreatic, or brain cancer. By generating viperin knockdown or stably expressing cancer cells, we showed that viperin, but not a mutant lacking its iron-sulfur cluster-binding motif, increased lipogenesis and glycolysis via inhibition of fatty acid β-oxidation in cancer cells. In the tumor microenvironment, deficiency of fatty acids and oxygen as well as production of IFNs upregulated viperin expression via the PI3K/AKT/mTOR/HIF-1α and JAK/STAT pathways. Moreover, viperin was primarily expressed in cancer stem-like cells (CSCs) and functioned to promote metabolic reprogramming and enhance CSC properties, thereby facilitating tumor growth in xenograft mouse models. Collectively, our data indicate that viperin-mediated metabolic alteration drives the metabolic phenotype and progression of cancer.

Original languageEnglish
Article numbere157302
JournalJournal of Clinical Investigation
Issue number24
Publication statusPublished - 2022 Dec 15

Bibliographical note

Funding Information:
This study was supported by grants from the National Research Foundation (NRF) of Korea, funded by the Ministry of Science and ICT (NRF-2021R1A2C1011092 and NRF-2022M3A9I2017587); a grant from the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare (HV20C0055); a faculty research grant from the Yonsei University College of Medicine for 2020 (6-2020-0230, to JYS) and the Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine. The authors thank Medical Illustration and Design, part of the Medical Research Support Services of Yonsei University College of Medicine, for all artistic support related to this work.

Publisher Copyright:
© 2022, Choi et al.

All Science Journal Classification (ASJC) codes

  • Medicine(all)


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