Oncosuppressive and oncogenic activity of the sphingolipid-metabolizing enzyme β-galactosylceramidase

Belleri, Mirella; Chiodelli, Paola; Corli, Marzia; Capra, Miriam; Presta, Marco

doi:10.1016/j.bbcan.2021.188675

Cited by 10 publications

(8 citation statements)

References 48 publications

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“…Thus far, only limited information has been available about the effect of the modulation of GALC activity on the lipidome, mainly obtained by the analysis of tissues harvested from adult twitcher mice or genetically modified cell lines [reviewed in [46] ]. In addition, even though scattered evidence indicates that alterations of the central and peripheral nervous system are observed in human Krabbe fetuses [9] , [10] , no data were available about the effects of the lack of GALC activity on the lipidome of developing organisms.…”

Section: Discussionmentioning

confidence: 99%

Impact of an irreversible β-galactosylceramidase inhibitor on the lipid profile of zebrafish embryos

Guerra,

Belleri,

Paiardi

et al. 2024

Computational and Structural Biotechnology Journal

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Section: Discussionmentioning

confidence: 99%

Impact of an irreversible β-galactosylceramidase inhibitor on the lipid profile of zebrafish embryos

Guerra,

Belleri,

Paiardi

et al. 2024

Computational and Structural Biotechnology Journal

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“…Alterations in the metabolism of sphingolipids, including the tumor suppressor ceramide, exert a deep impact on melanoma [ 57 , 58 , 59 , 60 ]. GALC is a lysosomal sphingolipid-metabolizing enzyme that catalyzes the removal of galactose from terminal β-galactose-containing sphingolipids, including β-galactosylceramide [ 11 , 12 ]. Previous observations have shown that GALC may exert pro-oncogenic functions in human melanoma [ 13 , 15 ].…”

Section: Discussionmentioning

confidence: 99%

“…The lysosomal acid hydrolase β-galactosylceramidase (GALC; EC 3.2.1.46) catalyzes the cleavage of β-galactose from β-galactosylceramide and other sphingolipids [ 11 , 12 ]. Observations in our laboratory indicate that GALC might function as an oncogenic enzyme in human melanoma.…”

Section: Introductionmentioning

confidence: 99%

Proteomic Analysis Highlights the Impact of the Sphingolipid Metabolizing Enzyme β-Galactosylceramidase on Mitochondrial Plasticity in Human Melanoma

Capoferri,

Mignani,

Manfredi

et al. 2024

IJMS

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Mitochondrial plasticity, marked by a dynamism between glycolysis and oxidative phosphorylation due to adaptation to genetic and microenvironmental alterations, represents a characteristic feature of melanoma progression. Sphingolipids play a significant role in various aspects of cancer cell biology, including metabolic reprogramming. Previous observations have shown that the lysosomal sphingolipid-metabolizing enzyme β-galactosylceramidase (GALC) exerts pro-oncogenic functions in melanoma. Here, mining the cBioPortal for a Cancer Genomics data base identified the top 200 nuclear-encoded genes whose expression is negatively correlated with GALC expression in human melanoma. Their categorization indicated a significant enrichment in Gene Ontology terms and KEGG pathways related to mitochondrial proteins and function. In parallel, proteomic analysis by LC-MS/MS of two GALC overexpressing human melanoma cell lines identified 98 downregulated proteins when compared to control mock cells. Such downregulation was confirmed at a transcriptional level by a Gene Set Enrichment Analysis of the genome-wide expression profiling data obtained from the same cells. Among the GALC downregulated proteins, we identified a cluster of 42 proteins significantly associated with GO and KEGG categorizations related to mitochondrion and energetic metabolism. Overall, our data indicate that changes in GALC expression may exert a significant impact on mitochondrial plasticity in human melanoma cells.

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“…GALC (β-galactose ceramidase) is a lysosomal enzyme that removes β-galactose from β-galactose ceramide, leading to the tumor suppressor metabolite ceramide, a tumor suppressor metabolite formation. Recent observations suggest that GALC may have opposing effects on tumor growth by acting as a tumor suppressor or oncogenic enzyme (Belleri et al 2022). Targeted correction of the BACE2/TMEM38B axis leads to intracellular calcium release depletion and inhibits tumor progression.…”

Section: Discussionmentioning

confidence: 99%

Development of an integrated machine learning-based approach utilizing NK cell marker genes for prostate cancer prognosis and treatment response characteristics

Maimaitiyimin,

An,

Xing

et al. 2023

Preprint

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Background Despite prostate cancer's (PCa) highly variable behavior and unclear response to immunotherapy, the importance of NK cells isn't comprehensively studied. Our study aimed to use a robust computational framework to consider NK cell marker gene signatures (NKCMGS) from 1,072 global PCa patients, intending to establish a reliable biomarker that can prognose and predict immunotherapy response. Methods NK cell-related biomarkers were studied in PRAD patients from six worldwide cohorts, creating a reliable NKCMGS biomarker using 101 genes and varied machine learning techniques. NKCMGS was further analyzed immunologically, providing new immunotherapy response and prognosis perspectives. Results The NKCMGS integrated 13 key genes, effectively classifying patients into high- and low-risk groups. Survival curves drawn from NKCMGS scores, age, T stage, and Gleason scores, established the reliable prognostic trait of NKCMGS. Biologically, high-scored NKCMGS indicated enhanced fatty acid and β-alanine metabolism pathways, while low scores showed enrichment in DNA repair and replication, homologous recombination, and cell cycle pathways. Moreover, low-risk patients demonstrated higher drug sensitivity, thus suggesting the potential of NKCMGS in predicting immune checkpoint inhibitor effectiveness. Conclusion Our robust machine learning framework, integrated with NKCMGS, show significant potential for providing personalized risk assessment and valuable treatment strategies for PCa patients.

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Oncosuppressive and oncogenic activity of the sphingolipid-metabolizing enzyme β-galactosylceramidase

Cited by 10 publications

References 48 publications

Impact of an irreversible β-galactosylceramidase inhibitor on the lipid profile of zebrafish embryos

Impact of an irreversible β-galactosylceramidase inhibitor on the lipid profile of zebrafish embryos

Proteomic Analysis Highlights the Impact of the Sphingolipid Metabolizing Enzyme β-Galactosylceramidase on Mitochondrial Plasticity in Human Melanoma

Development of an integrated machine learning-based approach utilizing NK cell marker genes for prostate cancer prognosis and treatment response characteristics

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