IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v8y2017i1d10.1038_ncomms15280.html
   My bibliography  Save this article

The essential role of YAP O-GlcNAcylation in high-glucose-stimulated liver tumorigenesis

Author

Listed:
  • Xiao Zhang

    (Shanghai Tenth People’s Hospital of Tongji University)

  • Yongxia Qiao

    (School of Public Health, Shanghai Jiaotong University School of Medicine)

  • Qi Wu

    (Shanghai Tenth People’s Hospital of Tongji University)

  • Yan Chen

    (Shanghai Tenth People’s Hospital of Tongji University)

  • Shaowu Zou

    (Shanghai Tenth People’s Hospital of Tongji University)

  • Xiangfan Liu

    (Faculty of Medical Laboratory Science, Shanghai Jiaotong University School of Medicine)

  • Guoqing Zhu

    (Shanghai Tenth People’s Hospital of Tongji University)

  • Yinghui Zhao

    (Shanghai Tenth People’s Hospital of Tongji University)

  • Yuxin Chen

    (Shanghai Tenth People’s Hospital of Tongji University)

  • Yongchun Yu

    (Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine)

  • Qiuhui Pan

    (Shanghai Tenth People’s Hospital of Tongji University
    Present address: Department of Laboratory Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China)

  • Jiayi Wang

    (Shanghai Tenth People’s Hospital of Tongji University)

  • Fenyong Sun

    (Shanghai Tenth People’s Hospital of Tongji University)

Abstract

O-GlcNAcylation has been implicated in the tumorigenesis of various tissue origins, but its function in liver tumorigenesis is not clear. Here, we demonstrate that O-GlcNAcylation can enhance the expression, stability and function of Yes-associated protein (YAP), the downstream transcriptional regulator of the Hippo pathway and a potent oncogenic factor in liver cancer. O-GlcNAcylation induces transformative phenotypes of liver cancer cells in a YAP-dependent manner. An O-GlcNAc site of YAP was identified at Thr241, and mutating this site decreased the O-GlcNAcylation, stability, and pro-tumorigenic capacities of YAP, while increasing YAP phosphorylation. Importantly, we found via in vitro cell-based and in vivo mouse model experiments that O-GlcNAcylation of YAP was required for high-glucose-induced liver tumorigenesis. Interestingly, a positive feedback between YAP and global cellular O-GlcNAcylation is also uncovered. We conclude that YAP O-GlcNAcylation is a potential therapeutic intervention point for treating liver cancer associated with high blood glucose levels and possibly diabetes.

Suggested Citation

  • Xiao Zhang & Yongxia Qiao & Qi Wu & Yan Chen & Shaowu Zou & Xiangfan Liu & Guoqing Zhu & Yinghui Zhao & Yuxin Chen & Yongchun Yu & Qiuhui Pan & Jiayi Wang & Fenyong Sun, 2017. "The essential role of YAP O-GlcNAcylation in high-glucose-stimulated liver tumorigenesis," Nature Communications, Nature, vol. 8(1), pages 1-15, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15280
    DOI: 10.1038/ncomms15280
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms15280
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms15280?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
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Yi Lei & Qiangyun Liu & Binggui Chen & Fangfang Wu & Yiming Li & Xue Dong & Nina Ma & Ziru Wu & Yanfang Zhu & Lu Wang & Yuxin Fu & Yuming Liu & Yinting Song & Mei Du & Heng Zhang & Jidong Zhu & Timoth, 2024. "Protein O-GlcNAcylation coupled to Hippo signaling drives vascular dysfunction in diabetic retinopathy," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    2. Na Zhang & Yang Meng & Song Mao & Huiling Ni & Canhua Huang & Licong Shen & Kun Fu & Lu Lv & Chunhong Yu & Piyanat Meekrathok & Chunmei Kuang & Fang Chen & Yu Zhang & Kai Yuan, 2025. "FBXO31-mediated ubiquitination of OGT maintains O-GlcNAcylation homeostasis to restrain endometrial malignancy," Nature Communications, Nature, vol. 16(1), pages 1-22, 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:8:y:2017:i:1:d:10.1038_ncomms15280. 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.

    We have no bibliographic references for this item. You can help adding them by using 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.