New era of research on cancer‐associated glycosphingolipids

Furukawa, Koichi; Ohmi, Yuhsuke; Ohkawa, Yuki; Bhuiyan, Robiul H.; Zhang, Pu; Tajima, Orie; Hashimoto, Noboru; Hamamura, Kazunori

doi:10.1111/cas.14005

Cited by 68 publications

(72 citation statements)

References 48 publications

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“…Monosialo-gangliosides GM3 and GM1 have been described to suppress the malignant properties of some cancer cells. For example, GM1 expression in tumorigenic H-ras-transformed NIH3T3 induces the suppression of proliferation [32,33]. On the contrary, disialo-gangliosides GD2 and GD3 are considered as tumor-associated carbohydrate antigens (TACA), especially in neuroectoderm-derived cancers and sarcoma [34].…”

Section: Expression Of Gangliosides In Normal and Pathological Conditmentioning

confidence: 99%

“…Cancer-associated GSLs are not only tumor markers, but also exhibit important biological functions generated by glycolipid-enriched membrane microdomains, also named lipid rafts. The implication of specific gangliosides in the malignant properties of cancer cells is now better understood [32,42]. Raft-associated proteins, such as growth factor receptor integrins, are cis-interacting molecules with GSLs, resulting in the modulation of cell signals mediated by those receptors at the cell surface.…”

Section: Expression Of Gangliosides In Normal and Pathological Conditmentioning

confidence: 99%

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O-acetylated Gangliosides as Targets for Cancer Immunotherapy

Cavdarli

Delannoy

Groux-Degroote

2020

Cells

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O-acetylation of sialic acid residues is one of the main modifications of gangliosides, and modulates ganglioside functions.O-acetylation of gangliosides is dependent on sialyl-O-acetyltransferases and sialyl-O-acetyl-esterase activities. CAS1 Domain-Containing Protein 1 (CASD1) is the only human sialyl-O-acetyltransferases (SOAT) described until now. O-acetylated ganglioside species are mainly expressed during embryonic development and in the central nervous system in healthy adults, but are re-expressed during cancer development and are considered as markers of cancers of neuroectodermal origin. However, the specific biological roles of O-acetylated gangliosides in developing and malignant tissues have not been extensively studied, mostly because of the requirement of specific approaches and tools for sample preparation and analysis. In this review, we summarize our current knowledge of ganglioside biosynthesis and expression in normal and pathological conditions, of ganglioside O-acetylation analysis and expression in cancers, and of the possible use of O-acetylated gangliosides as targets for cancer immunotherapy. a potential functional significance of ganglioside O-acetylation in cancer. The use of O-acetylated gangliosides as targets for cancer immunotherapy is also discussed. Ganglioside Structures and BiosynthesisGangliosides are acidic GSL containing from one to five sialic acids residues. They are mainly, but not exclusively, derived from ganglio-series GSL (GgCer) that result from the substitution of a ceramide (Cer) by the tetrasaccharide core Galβ1-3GalNAcβ1-4Galβ1-4Glcβ (Gg4). In different cell types and tissues, gangliosides are usually found as a mixture of di-, tri-and tetrasaccharide cores substituted by one or more sialic acid residues [1,5]. The biosynthesis of gangliosides takes place in the Golgi apparatus and starts by the transfer of sialic acid residues to lactosylceramide (LacCer) by specific sialyltransferases, i.e., the CMP-Neu5Ac: LacCer α2,3-sialyltransferase ST3Gal V (GM3 synthase) [6], the CMP-Neu5Ac: GM3 α2,8-sialyltransferase ST8Sia I (GD3 synthase) [7] and the CMP-Neu5Ac: GD3 α2,8-sialyltransferase ST8Sia V [8], that show high specificity toward glycolipid substrates [9]. Thus, LacCer, GM3, GD3 and GT3 are the precursors for 0-, a-, b-and c-series gangliosides, respectively (Figure 1).

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Section: Expression Of Gangliosides In Normal and Pathological Conditmentioning

confidence: 99%

Section: Expression Of Gangliosides In Normal and Pathological Conditmentioning

confidence: 99%

O-acetylated Gangliosides as Targets for Cancer Immunotherapy

Cavdarli

Delannoy

Groux-Degroote

2020

Cells

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“…They have been shown to be involved in development of neurological and neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease, Lewy body dementia, and frontotemporal dementia. In addition, cancer-associated glycosphingolipids have been used as markers for diagnosis and targets for immunotherapy of malignant tumors (Furukawa et al, 2019). In addition, cancer-associated glycosphingolipids have been used as markers for diagnosis and targets for immunotherapy of malignant tumors (Furukawa et al, 2019).…”

Section: Glycolipidomicsmentioning

confidence: 99%

“…In addition, cancer-associated glycosphingolipids have been used as markers for diagnosis and targets for immunotherapy of malignant tumors (Furukawa et al, 2019). In addition, cancer-associated glycosphingolipids have been used as markers for diagnosis and targets for immunotherapy of malignant tumors (Furukawa et al, 2019). Recent advancements in glycolipid biomarker discovery by mass spectrometry are reviewed in Dehelean et al (2019).…”

Section: Glycolipidomicsmentioning

confidence: 99%

Rise of Systems Glycobiology and Personalized Glycomedicine: Why and How to Integrate Glycomics with Multiomics Science?

Kunej

2019

OMICS: A Journal of Integrative Biology

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Glycomics is a rapidly emerging subspecialty of system sciences that evaluates the structures and functions of glycans in biological systems. Moreover, glycomics informs allied scholarships such as systems glycobiology and personalized glycomedicine that collectively aim to explain the role of glycans in person-to-person and between-population variations in disease susceptibility and response to health interventions such as drugs, nutrition, and vaccines. For glycomics to make greater, systems-scale, contributions to biology and medical research, it is facing a new developmental challenge: transition from single omics to multiomics integrative technology platforms. A comprehensive map of all possible connections between glycomics and other omics types has not yet been developed. Glycomics aims to discover a complex interplay of molecular interactions; however, little is known about the regulatory networks controlling these complex processes. In addition, the glycomics knowledgebase is presently scattered across various publications and databases, and therefore does not enable a holistic or systems view of this study field. Therefore, researchers are not always aware, for example, that a given analyzed genetic locus is linked with glycans, and that there are also glycomics determinants of complex phenotypes in health and biology. This review presents several published examples of glycomics science in association with other omics levels, such as genomics, transcriptomics, proteomics, metabolomics, epigenomics, ncRNomics, lipidomics, and interactomics. I also highlight the salient knowledge gaps and suggest future research directions. Understanding the interconnections of glycomics with other omics technologies will facilitate multiomics science and knowledge integration, enhance development of systems glycobiology and personalized glycomedicine.

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“…An optimal level of ganglioside expression is required to maintain membrane integrity [3]. Indeed, abnormal expression of gangliosides in tissue cells is associated with a variety of diseases, such as diabetes [4], neurologic diseases [5], and cancer [6]. Thus, a number of studies have been conducted to enhance understanding of the biosynthesis and metabolism of gangliosides as new targets for the prevention and treatment of these diseases.…”

Section: Introductionmentioning

confidence: 99%

Dietary Control of Ganglioside Expression in Mammalian Tissues

Okuda¹

2019

IJMS

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Gangliosides are series of glycosphingolipids containing sialic acids in the oligosaccharide portion in mammalian cells. Gangliosides are a component of cellular membranes and play roles in modulating membrane function and the activity of membrane proteins. Abnormal expression and metabolism of gangliosides lead to the onset of several conditions in humans, such as neurologic diseases, diabetes, and cancer. A number of studies have been carried out to date to investigate the role of gangliosides in these diseases, and the effect of diet on tissue expression of gangliosides has recently become a topic of interest in this field. As gangliosides are degraded in the intestinal tract, ingested food-derived gangliosides are not directly absorbed into tissues in vivo, but the degradation products can be absorbed and affect ganglioside expression in the tissues. Recent studies have also shown that the expression of gangliosides in tissue cells can be indirectly induced by controlling the expression of ganglioside metabolism-related genes via the diet. These results indicate that dietary control can regulate the expression levels of gangliosides in tissues, which is expected to play a role in preventing and treating ganglioside-related diseases. This review introduces recent studies on the effect of diet on the expression of gangliosides in tissues, with a focus on our findings.

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New era of research on cancer‐associated glycosphingolipids

Cited by 68 publications

References 48 publications

O-acetylated Gangliosides as Targets for Cancer Immunotherapy

O-acetylated Gangliosides as Targets for Cancer Immunotherapy

Rise of Systems Glycobiology and Personalized Glycomedicine: Why and How to Integrate Glycomics with Multiomics Science?

Dietary Control of Ganglioside Expression in Mammalian Tissues

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