2. Academic Validation
  3. OGT/HIF-2α axis promotes the progression of clear cell renal cell carcinoma and regulates its sensitivity to ferroptosis

OGT/HIF-2α axis promotes the progression of clear cell renal cell carcinoma and regulates its sensitivity to ferroptosis

  • iScience. 2023 Oct 5;26(11):108148. doi: 10.1016/j.isci.2023.108148.
Zhou Yang 1 2 3,  Xiyi Wei 1,  Chengjian Ji 1,  Xiaohan Ren 1,  Wei Su 3 4,  Yichun Wang 1,  Jingwan Zhou 5,  Zheng Zhao 5,  Pengcheng Zhou 5,  Kejie Zhao 5,  Bing Yao 5 6,  Ninghong Song 1 2,  Chao Qin 1 2
Affiliations

Affiliations

  • 1 The State Key Lab of Reproductive, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
  • 2 Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
  • 3 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
  • 4 Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
  • 5 National Experimental Teaching Center of Basic Medical Science, Nanjing Medical University, Nanjing, China.
  • 6 Department of Medical Genetics, Nanjing Medical University, Nanjing, China.
PMID: 37915611 DOI: 10.1016/j.isci.2023.108148
Abstract

O-GlcNAc transferase (OGT) acts in the development of various cancers, but its role in clear cell renal cell carcinoma (ccRCC) remains unclear. In this study, we found that OGT was upregulated in ccRCC and this upregulation was associated with a worse survival. Moreover, OGT promoted the proliferation, clone formation, and invasion of VHL-mutated ccRCC cells. Mechanistically, OGT increased the protein level of hypoxia-inducible factor-2α (HIF-2α) (the main driver of the clear cell phenotype) by repressing ubiquitin‒proteasome system-mediated degradation. Interestingly, the OGT/HIF-2α axis conferred ccRCC a high sensitivity to Ferroptosis. In conclusion, OGT promotes the progression of VHL-mutated ccRCC by inhibiting the degradation of HIF-2α, and agents that can modulate the OGT/HIF-2α axis may exert therapeutic effects on mutated VHL ccRCC.

Keywords

Cancer; Functional aspects of cell biology; In vitro toxicology; Molecular biology experimental approach; Molecular network.

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