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O‑GlcNAcylation as an emerging molecular target for cholangiocarcinoma therapy (Review)

Purin Charoensuksai1, Siwanon Jirawatnotai2

  • 1Department of Biomedicine and Health Informatics, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand.

Oncology Reports
|July 19, 2025
PubMed

Insights

Aberrant O-GlcNAcylation and O-GlcNAc transferase (OGT) drive cancer progression. Targeting OGT and O-GlcNAc signaling shows promise for treating cholangiocarcinoma and other cancers.

Area of Science:

  • Biochemistry
  • Oncology
  • Molecular Biology

Background:

  • Aberrant O-GlcNAcylation and O-GlcNAc transferase (OGT) upregulation are implicated in cancer pathogenesis.
  • Cholangiocarcinoma (CCA) is an aggressive bile duct cancer with poor outcomes, necessitating novel therapeutic strategies.
  • Hyperactive O-GlcNAcylation and OGT upregulation are observed in CCA.

Purpose of the Study:

  • To review the impact of O-GlcNAcylation on CCA and cancer hallmarks.
  • To explore potential mechanistic connections using insights from other gastrointestinal cancers.
  • To discuss the therapeutic potential of targeting OGT and O-GlcNAcylation in CCA.

Main Methods:

  • Literature review of O-GlcNAcylation in cancer.
  • Analysis of OGT's role in cancer hallmarks like proliferation and metastasis.
  • Synthesis of findings from CCA and related gastrointestinal cancers.

Main Results:

  • O-GlcNAcylation influences cancer hallmarks including proliferation, metastasis, metabolism, angiogenesis, cell death, and inflammation.
  • OGT and O-GlcNAc signaling are critical drivers in CCA pathogenesis.
  • Insights from other cancers provide context for CCA-specific mechanisms.

Conclusions:

  • Targeting OGT and O-GlcNAc signaling represents a viable therapeutic strategy for cholangiocarcinoma.
  • Further research is warranted to fully elucidate the role of O-GlcNAcylation in CCA.
  • O-GlcNAcylation modulation offers a promising avenue for novel cancer therapies.
Keywords:
O‑GlcNAc transferaseO‑GlcNAcylationO‑GlcNAcylation‑targeted therapycancer precision medicinecholangio-carcinomasugar metabolism in cancer

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