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Nutrient sensor O-GlcNAc transferase controls cancer lipid metabolism via SREBP-1 regulation

V L Sodi1, Z A Bacigalupa1, C M Ferrer1

  • 1Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA, USA.

Oncogene
|October 24, 2017
PubMed

Insights

Elevated O-GlcNAcylation, linked to cancer, impacts lipid metabolism. O-GlcNAc transferase (OGT) regulates SREBP-1, a key lipid regulator, influencing cancer cell survival and growth.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Elevated O-GlcNAcylation is implicated in diseases like diabetes and cancer.
  • O-GlcNAc transferase (OGT) is upregulated in various cancers, and its inhibition suppresses oncogenesis.

Purpose of the Study:

  • To investigate the role of O-GlcNAcylation in modulating lipid metabolism within cancer cells.
  • To elucidate the mechanism by which OGT influences lipid regulation and cancer progression.

Main Methods:

  • Investigated OGT's effect on lipid metabolism and SREBP-1 expression in cancer cells.
  • Utilized genetic and pharmacological inhibition of OGT.
  • Examined the role of AMP-activated protein kinase (AMPK) in OGT-mediated SREBP-1 regulation.
  • Assessed the impact of SREBP-1 overexpression on OGT-suppressed phenotypes.

Main Results:

  • O-GlcNAcylation was found to modulate lipid metabolism in cancer cells.
  • OGT regulates the expression of sterol regulatory element binding protein 1 (SREBP-1), a master lipid regulator.
  • OGT controls SREBP-1 protein levels via AMPK signaling.
  • Overexpression of SREBP-1 rescued lipogenic defects and tumor growth upon OGT suppression.

Conclusions:

  • A novel link between O-GlcNAcylation, lipid metabolism, and SREBP-1 regulation in cancer was identified.
  • OGT plays a critical role in controlling cancer cell survival and lipid synthesis through SREBP-1.
  • O-GlcNAc signaling is crucial for integrating nutritional status with lipid metabolism regulation in cancer.

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