IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-33859-9.html
   My bibliography  Save this article

ATF4-dependent fructolysis fuels growth of glioblastoma multiforme

Author

Listed:
  • Chao Chen

    (Chinese Academy of Sciences)

  • Zhenxing Zhang

    (Chinese Academy of Sciences)

  • Caiyun Liu

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Bin Wang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Ping Liu

    (Chinese Academy of Sciences)

  • Shu Fang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Fan Yang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Yongping You

    (The First Affiliated Hospital of Nanjing Medical University
    Nanjing Medical University)

  • Xinjian Li

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

Abstract

Excessive consumption of fructose in the Western diet contributes to cancer development. However, it is still unclear how cancer cells coordinate glucose and fructose metabolism during tumor malignant progression. We demonstrate here that glioblastoma multiforme (GBM) cells switch their energy supply from glycolysis to fructolysis in response to glucose deprivation. Mechanistically, glucose deprivation induces expression of two essential fructolytic proteins GLUT5 and ALDOB through selectively activating translation of activating transcription factor 4 (ATF4). Functionally, genetic or pharmacological disruption of ATF4-dependent fructolysis significantly inhibits growth and colony formation of GBM cells in vitro and GBM growth in vivo. In addition, ATF4, GLUT5, and ALDOB levels positively correlate with each other in GBM specimens and are poor prognostic indicators in GBM patients. This work highlights ATF4-dependent fructolysis as a metabolic feature and a potential therapeutic target for GBM.

Suggested Citation

  • Chao Chen & Zhenxing Zhang & Caiyun Liu & Bin Wang & Ping Liu & Shu Fang & Fan Yang & Yongping You & Xinjian Li, 2022. "ATF4-dependent fructolysis fuels growth of glioblastoma multiforme," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33859-9
    DOI: 10.1038/s41467-022-33859-9
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-33859-9
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-33859-9?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Zhenxing Zhang & Xin Li & Fan Yang & Chao Chen & Ping Liu & Yi Ren & Pengkai Sun & Zixiong Wang & Yongping You & Yi-Xin Zeng & Xinjian Li, 2021. "DHHC9-mediated GLUT1 S-palmitoylation promotes glioblastoma glycolysis and tumorigenesis," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    2. Andrew V. Anzalone & Peyton B. Randolph & Jessie R. Davis & Alexander A. Sousa & Luke W. Koblan & Jonathan M. Levy & Peter J. Chen & Christopher Wilson & Gregory A. Newby & Aditya Raguram & David R. L, 2019. "Search-and-replace genome editing without double-strand breaks or donor DNA," Nature, Nature, vol. 576(7785), pages 149-157, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Lisa Maria Riedmayr & Klara Sonnie Hinrichsmeyer & Stefan Bernhard Thalhammer & David Manuel Mittas & Nina Karguth & Dina Yehia Otify & Sybille Böhm & Valentin Johannes Weber & Michael David Bartosche, 2023. "mRNA trans-splicing dual AAV vectors for (epi)genome editing and gene therapy," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    2. Tian Zhou & Xinyi Zhu & Zhizhong Ye & Yong-Fei Wang & Chao Yao & Ning Xu & Mi Zhou & Jianyang Ma & Yuting Qin & Yiwei Shen & Yuanjia Tang & Zhihua Yin & Hong Xu & Yutong Zhang & Xiaoli Zang & Huihua D, 2022. "Lupus enhancer risk variant causes dysregulation of IRF8 through cooperative lncRNA and DNA methylation machinery," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Guiquan Zhang & Yao Liu & Shisheng Huang & Shiyuan Qu & Daolin Cheng & Yuan Yao & Quanjiang Ji & Xiaolong Wang & Xingxu Huang & Jianghuai Liu, 2022. "Enhancement of prime editing via xrRNA motif-joined pegRNA," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    4. Raed Ibraheim & Phillip W. L. Tai & Aamir Mir & Nida Javeed & Jiaming Wang & Tomás C. Rodríguez & Suk Namkung & Samantha Nelson & Eraj Shafiq Khokhar & Esther Mintzer & Stacy Maitland & Zexiang Chen &, 2021. "Self-inactivating, all-in-one AAV vectors for precision Cas9 genome editing via homology-directed repair in vivo," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    5. Ronghao Chen & Yu Cao & Yajing Liu & Dongdong Zhao & Ju Li & Zhihui Cheng & Changhao Bi & Xueli Zhang, 2023. "Enhancement of a prime editing system via optimal recruitment of the pioneer transcription factor P65," Nature Communications, Nature, vol. 14(1), pages 1-8, December.
    6. Xiangyang Li & Guiquan Zhang & Shisheng Huang & Yao Liu & Jin Tang & Mingtian Zhong & Xin Wang & Wenjun Sun & Yuan Yao & Quanjiang Ji & Xiaolong Wang & Jianghuai Liu & Shiqiang Zhu & Xingxu Huang, 2023. "Development of a versatile nuclease prime editor with upgraded precision," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    7. Martin Peterka & Nina Akrap & Songyuan Li & Sandra Wimberger & Pei-Pei Hsieh & Dmitrii Degtev & Burcu Bestas & Jack Barr & Stijn Plassche & Patricia Mendoza-Garcia & Saša Šviković & Grzegorz Sienski &, 2022. "Harnessing DSB repair to promote efficient homology-dependent and -independent prime editing," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    8. Zhaohui Zhong & Guanqing Liu & Zhongjie Tang & Shuyue Xiang & Liang Yang & Lan Huang & Yao He & Tingting Fan & Shishi Liu & Xuelian Zheng & Tao Zhang & Yiping Qi & Jian Huang & Yong Zhang, 2023. "Efficient plant genome engineering using a probiotic sourced CRISPR-Cas9 system," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    9. Qichen Yuan & Xue Gao, 2022. "Multiplex base- and prime-editing with drive-and-process CRISPR arrays," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    10. Huawei Tong & Haoqiang Wang & Xuchen Wang & Nana Liu & Guoling Li & Danni Wu & Yun Li & Ming Jin & Hengbin Li & Yinghui Wei & Tong Li & Yuan Yuan & Linyu Shi & Xuan Yao & Yingsi Zhou & Hui Yang, 2024. "Development of deaminase-free T-to-S base editor and C-to-G base editor by engineered human uracil DNA glycosylase," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    11. You Li & Zhiqiang Li & Ruiling Chen & Min Lian & Hanxiao Wang & Yiran Wei & Zhengrui You & Jun Zhang & Bo Li & Yikang Li & Bingyuan Huang & Yong Chen & Qiaoyan Liu & Zhuwan Lyu & Xueying Liang & Qi Mi, 2023. "A regulatory variant at 19p13.3 is associated with primary biliary cholangitis risk and ARID3A expression," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    12. Kun Jia & Yan-ru Cui & Shisheng Huang & Peihong Yu & Zhengxing Lian & Peixiang Ma & Jia Liu, 2022. "Phage peptides mediate precision base editing with focused targeting window," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    13. Xiangfeng Kong & Hainan Zhang & Guoling Li & Zikang Wang & Xuqiang Kong & Lecong Wang & Mingxing Xue & Weihong Zhang & Yao Wang & Jiajia Lin & Jingxing Zhou & Xiaowen Shen & Yinghui Wei & Na Zhong & W, 2023. "Engineered CRISPR-OsCas12f1 and RhCas12f1 with robust activities and expanded target range for genome editing," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    14. Péter István Kulcsár & András Tálas & Zoltán Ligeti & Sarah Laura Krausz & Ervin Welker, 2022. "SuperFi-Cas9 exhibits remarkable fidelity but severely reduced activity yet works effectively with ABE8e," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    15. You-Jeong Kim & Dayoung Yun & Jungjoon K. Lee & Cheulhee Jung & Aram J. Chung, 2024. "Highly efficient CRISPR-mediated genome editing through microfluidic droplet cell mechanoporation," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    16. Yi-Li Feng & Qian Liu & Ruo-Dan Chen & Si-Cheng Liu & Zhi-Cheng Huang & Kun-Ming Liu & Xiao-Ying Yang & An-Yong Xie, 2022. "DNA nicks induce mutational signatures associated with BRCA1 deficiency," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    17. Xiaosa Li & Lina Zhou & Bao-Qing Gao & Guangye Li & Xiao Wang & Ying Wang & Jia Wei & Wenyan Han & Zixian Wang & Jifang Li & Runze Gao & Junjie Zhu & Wenchao Xu & Jing Wu & Bei Yang & Xiaodong Sun & L, 2022. "Highly efficient prime editing by introducing same-sense mutations in pegRNA or stabilizing its structure," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    18. Michael Kosicki & Felicity Allen & Frances Steward & Kärt Tomberg & Yangyang Pan & Allan Bradley, 2022. "Cas9-induced large deletions and small indels are controlled in a convergent fashion," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    19. Peter N. Ciaccia & Zhuobin Liang & Anabel Y. Schweitzer & Eli Metzner & Farren J. Isaacs, 2024. "Enhanced eMAGE applied to identify genetic factors of nuclear hormone receptor dysfunction via combinatorial gene editing," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    20. Marion Rosello & Malo Serafini & Luca Mignani & Dario Finazzi & Carine Giovannangeli & Marina C. Mione & Jean-Paul Concordet & Filippo Del Bene, 2022. "Disease modeling by efficient genome editing using a near PAM-less base editor in vivo," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33859-9. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.