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O-GlcNAcylation links oncogenic signals and cancer epigenetics

Lidong Sun1, Suli Lv2, Tanjing Song3

  • 1Department of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China. LidongSun@hust.edu.cn.

Discover Oncology
|February 24, 2022
PubMed

Insights

Oncogenic signals disrupt O-GlcNAcylation, a protein modification process, leading to epigenetic abnormalities common in cancer. Understanding this axis offers new therapeutic strategies for cancer treatment.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Biology

Background:

  • Epigenetic modifications are frequently dysregulated in cancer, presenting a therapeutic target.
  • O-GlcNAcylation, a dynamic post-translational modification, is regulated by the hexosamine biogenesis pathway (HBP) and enzymes O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA).
  • Aberrant O-GlcNAcylation is observed in various cancers, similar to epigenetic alterations.

Purpose of the Study:

  • To review how oncogenic signals influence HBP enzymes, OGT, and OGA in cancer.
  • To integrate the role of O-GlcNAcylation in regulating epigenetic machinery.
  • To propose a signaling axis connecting oncogenic signals, O-GlcNAcylation dysregulation, and epigenetic abnormalities in cancer.

Main Methods:

  • Literature review focusing on oncogenic signaling pathways.
  • Analysis of studies investigating O-GlcNAcylation and its enzymes (OGT, OGA).
  • Integration of data on epigenetic modifications and their regulation.

Main Results:

  • Oncogenic signals significantly impact HBP enzymes, OGT, and OGA activity in cancer cells.
  • O-GlcNAcylation directly influences numerous proteins involved in epigenetic regulation.
  • A clear link exists between oncogenic pathways, altered O-GlcNAcylation, and subsequent epigenetic changes.

Conclusions:

  • Dysregulation of O-GlcNAcylation by oncogenic factors contributes to cancer-associated epigenetic abnormalities.
  • The proposed signal axis provides a framework for understanding cancer development.
  • Elucidating this axis may reveal novel therapeutic targets for cancer intervention.
Keywords:
ChromatinEpigeneticsHexoamine biosynthesis pathwayHistoneO-GlcNAcylationOGAOGT

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