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Central Roles of Glucosylceramide in Driving Cancer Pathogenesis
Xueheng Zhao1,2, Manoj Kumar Pandey2,3
1Divisions of Pathology and Laboratory Medicine and Biomedical Informatics, Burnet Campus, 3333 Burnet Avenue, Cincinnati, OH 45229-3026, USA.
International Journal of Molecular Sciences
|October 29, 2025
Summary
Glucosylceramide (GlcCer), a bioactive lipid, is linked to cancer progression and drug resistance. Targeting GlcCer synthesis may offer new cancer therapies and biomarkers for tumor-predisposing diseases.
Area of Science:
- Biochemistry and Molecular Biology
- Cancer Biology and Oncology
- Metabolic Disorders
Background:
- Glucosylceramide (GlcCer) is a bioactive glycosphingolipid derived from ceramide.
- Dysregulation of GlcCer is linked to lysosomal storage disorders like Gaucher disease (GD).
- Emerging evidence highlights GlcCer's role in cancer initiation, progression, and drug resistance.
Purpose of the Study:
- To review recent advances in Glucosylceramide (GlcCer) biology.
- To emphasize GlcCer's roles in tumor-predisposing diseases and cancer.
- To explore GlcCer's potential as a biomarker and therapeutic target in oncology.
Main Methods:
- Literature review integrating recent scientific advances.
- Analysis of Glucosylceramide (GlcCer) metabolism and its associated signaling pathways.
- Examination of the role of UDP-glucose ceramide glucosyltransferase (UGCG) in cancer.
Main Results:
- Glucosylceramide (GlcCer) promotes cancer cell survival, growth, metastasis, and multidrug resistance.
- Aberrant upregulation of UDP-glucose ceramide glucosyltransferase (UGCG) drives oncogenic pathways (PI3K/Akt, MAPK, Wnt, NF-κB).
- Specific GlcCer species exhibit tissue-dependent functions, contributing to oncogenic potential.
- GlcCer metabolism is linked to inflammation, oxidative stress, and altered glucose utilization.
Conclusions:
- Glucosylceramide (GlcCer) acts as a critical metabolic node connecting inherited disorders and malignancy.
- GlcCer's involvement in key cancer pathways suggests its potential as a therapeutic target.
- Further research into GlcCer metabolism may yield novel biomarkers for cancer diagnosis and treatment.
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