AKR1B1-dependent fructose metabolism enhances malignancy of cancer cells

IF 13.7 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Qing Zhao, Bing Han, Lu Wang, Jia Wu, Siliang Wang, Zhenxing Ren, Shouli Wang, Haining Yang, Michele Carbone, Changsheng Dong, Gerry Melino, Wen-Lian Chen, Wei Jia
{"title":"AKR1B1-dependent fructose metabolism enhances malignancy of cancer cells","authors":"Qing Zhao, Bing Han, Lu Wang, Jia Wu, Siliang Wang, Zhenxing Ren, Shouli Wang, Haining Yang, Michele Carbone, Changsheng Dong, Gerry Melino, Wen-Lian Chen, Wei Jia","doi":"10.1038/s41418-024-01393-4","DOIUrl":null,"url":null,"abstract":"Fructose metabolism has emerged as a significant contributor to cancer cell proliferation, yet the underlying mechanisms and sources of fructose for cancer cells remain incompletely understood. In this study, we demonstrate that cancer cells can convert glucose into fructose through a process called the AKR1B1-mediated polyol pathway. Inhibiting the endogenous production of fructose through AKR1B1 deletion dramatically suppressed glycolysis, resulting in reduced cancer cell migration, inhibited growth, and the induction of apoptosis and cell cycle arrest. Conversely, the acceleration of endogenous fructose through AKR1B1 overexpression has been shown to significantly enhance cancer cell proliferation and migration with increased S cell cycle progression. Our findings highlight the crucial role of endogenous fructose in cancer cell malignancy and support the need for further investigation into AKR1B1 as a potential cancer therapeutic target.","PeriodicalId":9731,"journal":{"name":"Cell Death and Differentiation","volume":"31 12","pages":"1611-1624"},"PeriodicalIF":13.7000,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41418-024-01393-4.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Death and Differentiation","FirstCategoryId":"99","ListUrlMain":"https://www.nature.com/articles/s41418-024-01393-4","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Fructose metabolism has emerged as a significant contributor to cancer cell proliferation, yet the underlying mechanisms and sources of fructose for cancer cells remain incompletely understood. In this study, we demonstrate that cancer cells can convert glucose into fructose through a process called the AKR1B1-mediated polyol pathway. Inhibiting the endogenous production of fructose through AKR1B1 deletion dramatically suppressed glycolysis, resulting in reduced cancer cell migration, inhibited growth, and the induction of apoptosis and cell cycle arrest. Conversely, the acceleration of endogenous fructose through AKR1B1 overexpression has been shown to significantly enhance cancer cell proliferation and migration with increased S cell cycle progression. Our findings highlight the crucial role of endogenous fructose in cancer cell malignancy and support the need for further investigation into AKR1B1 as a potential cancer therapeutic target.

Abstract Image

Abstract Image

依赖 AKR1B1 的果糖代谢会增强癌细胞的恶性程度
果糖代谢已成为导致癌细胞增殖的一个重要因素,然而,人们对癌细胞获得果糖的基本机制和来源仍然知之甚少。在这项研究中,我们证明癌细胞可以通过一种名为 AKR1B1 介导的多元醇途径将葡萄糖转化为果糖。通过 AKR1B1 基因缺失抑制内源性果糖的产生,可显著抑制糖酵解,从而减少癌细胞迁移、抑制生长、诱导细胞凋亡和细胞周期停滞。相反,通过 AKR1B1 的过表达加速内源性果糖的生成,则会显著增强癌细胞的增殖和迁移,并增加 S 细胞周期的进展。我们的研究结果突显了内源性果糖在癌细胞恶变中的关键作用,并支持将 AKR1B1 作为潜在癌症治疗靶点进行进一步研究的必要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Cell Death and Differentiation
Cell Death and Differentiation 生物-生化与分子生物学
CiteScore
24.70
自引率
1.60%
发文量
181
审稿时长
3 months
期刊介绍: Mission, vision and values of Cell Death & Differentiation: To devote itself to scientific excellence in the field of cell biology, molecular biology, and biochemistry of cell death and disease. To provide a unified forum for scientists and clinical researchers It is committed to the rapid publication of high quality original papers relating to these subjects, together with topical, usually solicited, reviews, meeting reports, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信