Related Experiment Video
Updated: Aug 14, 2026
08:07
Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
Published on: April 12, 2019
High-Glucose Microenvironment Promotes Canine Osteosarcoma Cell Stemness via the HBP/O-GlcNAc Signaling Axis
Weiqian Wang1, Bingsong Yang1, Guangmin Zhang1
1Heilongjiang Provincial Key Laboratory of Pathogenic Mechanism for Animal Disease and Comparative Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150036, China.
Cells
|August 13, 2026
Summary
High glucose fuels canine osteosarcoma stemness by activating the hexosamine biosynthetic pathway (HBP) and O-linked N-acetylglucosamine (O-GlcNAc)ylation. Targeting these pathways offers new therapeutic strategies for osteosarcoma.
Area of Science:
- Molecular Biology
- Cancer Research
- Metabolic Pathways
Background:
- Osteosarcoma (OS) exhibits high metastatic potential and chemoresistance, driven by cancer stem cells (CSCs).
- Canine osteosarcoma (cOS) serves as a valuable model for human osteosarcoma (hOS).
- Aberrant glucose metabolism and the hexosamine biosynthetic pathway (HBP)/O-linked N-acetylglucosamine (O-GlcNAc)ylation are implicated in tumor progression, but their role in cOS stemness is unclear.
Purpose of the Study:
- To investigate the mechanisms by which high glucose, HBP, and O-GlcNAcylation regulate stemness in canine osteosarcoma cells.
- To identify potential therapeutic targets for osteosarcoma based on metabolic dysregulation.
Main Methods:
- Glucose gradient culture, untargeted metabolomics, and O-GlcNAc-modified proteomics were employed.
- In vitro gene silencing of key HBP enzymes (GFPT1, OGT, OGA) and in vivo xenograft models were utilized.
- Cellular functional assays and tumorigenesis assays assessed malignant phenotypes and stemness.
Main Results:
- High glucose significantly enhanced malignant phenotypes and stemness properties of cOS cells.
- HBP activation and increased O-GlcNAcylation were observed in a dose-dependent manner with high glucose.
- Silencing HBP/O-GlcNAcylation-related genes (GFPT1, OGT, OGA) suppressed malignant behaviors and stemness; OGT knockdown inhibited tumor growth in vivo.
- Proteomic analysis identified TLE3, NCOR1, and NOTCH2 as key O-GlcNAc-modified proteins involved in Wnt and Notch signaling.
Conclusions:
- High glucose activates the HBP and elevates O-GlcNAcylation, promoting stemness in canine osteosarcoma stem cells via modification of TLE3/NCOR1/NOTCH2.
- The HBP and O-GlcNAcylation are critical regulators of malignant progression and stemness maintenance in cOS.
- This study highlights novel metabolic targets, including the HBP and O-GlcNAcylation pathways, for precision therapy in osteosarcoma.
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