2. Academic Validation
  3. O-GlcNAcylation enhances sensitivity to RSL3-induced ferroptosis via the YAP/TFRC pathway in liver cancer

O-GlcNAcylation enhances sensitivity to RSL3-induced ferroptosis via the YAP/TFRC pathway in liver cancer

  • Cell Death Discov. 2021 Apr 16;7(1):83. doi: 10.1038/s41420-021-00468-2.
Guoqing Zhu  # 1,  Abduh Murshed  # 2,  Haojie Li 2,  Ji Ma 1,  Ni Zhen 1,  Miao Ding 1,  Jiabei Zhu 1,  Siwei Mao 1,  Xiaochen Tang 1,  Li Liu 3,  Fenyong Sun 2,  Lei Jin 4,  Qiuhui Pan 5
Affiliations

Affiliations

  • 1 Department of Clinical Laboratory Medicine, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, 200127, Shanghai, China.
  • 2 Department of Clinical Laboratory, Shanghai Tenth People's Hospital of Tongji University, 200072, Shanghai, China.
  • 3 Department of Clinical Laboratory, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, 200434, Shanghai, China.
  • 4 Faculty of Medical Laboratory, Shanghai University of Medicine and Health Sciences, 201318, Shanghai, China. [email protected].
  • 5 Department of Clinical Laboratory Medicine, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, 200127, Shanghai, China. [email protected].
  • # Contributed equally.
PMID: 33863873 DOI: 10.1038/s41420-021-00468-2
Abstract

Ferroptosis is a form of regulated cell death characterized by iron-dependent accumulation of lipid hydroperoxides to lethal levels. YAP has been reported to play a pivotal role in controlling ferroptotic death, and the expression of YAP is enhanced and stabilized by O-GlcNAcylation. However, whether O-GlcNAcylation can increase the sensitivity of hepatocellular carcinoma (HCC) cells to Ferroptosis remains unknown. In the present study, we found that O-GlcNAcylation increased the sensitivity of HCC cells to Ferroptosis via YAP. Moreover, YAP increased the iron concentration in HCC cells through transcriptional elevation of TFRC via its O-GlcNAcylation. With YAP knockdown or YAP-T241 mutation, the increased sensitivity to Ferroptosis induced by O-GlcNAcylation was abolished. In addition, the xenograft assay confirmed that O-GlcNAcylation increased Ferroptosis sensitivity via TFRC in vivo. In summary, we are the first to find that O-GlcNAcylation can increase Ferroptosis sensitivity in HCC cells via YAP/TFRC. Our work will provide a new basis for clinical therapeutic strategies for HCC patients.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-100887
    98.25%, Ferroptosis Inducer