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The interferon-inducible protein viperin controls cancer metabolic reprogramming to enhance cancer progression.
| Content Provider | Europe PMC |
|---|---|
| Author | Choi, Kyung Mi Kim, Jeong Jin Yoo, Jihye Kim, Ku Sul Gu, Youngeun Eom, John Jeong, Haengdueng Kim, Kyungeun Nam, Ki Taek Park, Young Soo Chung, Joon-Yong Seo, Jun-Young |
| Copyright Year | 2022 |
| Abstract | 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. |
| ISSN | 00219738 |
| Journal | The Journal of Clinical Investigation |
| Volume Number | 132 |
| PubMed Central reference number | PMC9753993 |
| Issue Number | 24 |
| PubMed reference number | 36227691 |
| e-ISSN | 15588238 |
| DOI | 10.1172/JCI157302 |
| Language | English |
| Publisher | American Society for Clinical Investigation |
| Publisher Date | 2022-12-15 |
| Access Restriction | Open |
| Rights License | This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. © 2022 Choi et al. |
| Subject Keyword | Metabolism Oncology Cancer Fatty acid oxidation Glucose metabolism |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine |
