ID | 63941 |
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Author |
Tsujimoto, Goki
Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
Ito, Rin
Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
Yoshikawa, Kei
Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
Ueki, Chihiro
Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
Okada, Nobuhiro
Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
Kaken ID
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Abstract | Reprogramming of glucose metabolism occurs in many human tumor types, and one of these, gluconeogenesis, is known to exhibit anti-tumor effects in hepatocellular carcinoma (HCC). The transcription factor NFYA regulates gluconeogenesis in the normal liver tissue, but the function of the NFYA-gluconeogenesis axis in cancer and the functional differences of NFYA splicing variants in the regulation of gluconeogenesis is still unclear. Here, we demonstrate that NFYAv2, the short-form variant, upregulates the transcription of a gluconeogenic enzyme PCK1. We further reveal that its regulation induces high ROS levels and energy crisis in HCC and promotes cell death. These indicate that the NFYAv2-gluconeogenesis axis has enhanced anti-tumor effects in HCC, suggesting that the axis may be a potential therapeutic target for HCC. Furthermore, Nfyav1-deficient mice, spontaneously overexpressing Nfyav2, had no increasing gluconeogenesis in the liver. Taken together, our results reveal NFYAv2-gluconeogenesis axis has anti-tumor effects and the potential for NFYAv2 to be a safer therapeutic target for HCC.
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Keywords | hepatocellular carcinoma (HCC)
cancer metabolism
gluconeogenesis
cell death
oxidative stress
NFYA
PCK1
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Published Date | 2022-08-25
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Publication Title |
Frontiers In Cell And Developmental Biology
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Volume | volume10
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Publisher | Frontiers Media SA
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Start Page | 983599
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ISSN | 2296-634X
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Content Type |
Journal Article
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language |
English
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OAI-PMH Set |
岡山大学
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Copyright Holders | © 2022 Tsujimoto, Ito, Yoshikawa, Ueki and Okada.
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File Version | publisher
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PubMed ID | |
DOI | |
Web of Science KeyUT | |
Related Url | isVersionOf https://doi.org/10.3389/fcell.2022.983599
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License | https://creativecommons.org/licenses/by/4.0/
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Funder Name |
Wesco Scientific Promotion Foundation
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助成番号 | 19K07640
22K07152
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