ID | 63941 |
フルテキストURL | |
著者 |
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
researchmap
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抄録 | 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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キーワード | hepatocellular carcinoma (HCC)
cancer metabolism
gluconeogenesis
cell death
oxidative stress
NFYA
PCK1
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発行日 | 2022-08-25
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出版物タイトル |
Frontiers In Cell And Developmental Biology
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巻 | 10巻
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出版者 | Frontiers Media SA
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開始ページ | 983599
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ISSN | 2296-634X
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資料タイプ |
学術雑誌論文
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言語 |
英語
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OAI-PMH Set |
岡山大学
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著作権者 | © 2022 Tsujimoto, Ito, Yoshikawa, Ueki and Okada.
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論文のバージョン | publisher
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PubMed ID | |
DOI | |
Web of Science KeyUT | |
関連URL | isVersionOf https://doi.org/10.3389/fcell.2022.983599
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ライセンス | https://creativecommons.org/licenses/by/4.0/
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助成機関名 |
Wesco Scientific Promotion Foundation
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助成番号 | 19K07640
22K07152
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