Glycans in cancer and inflammation — potential for therapeutics and diagnostics

Dube, Danielle H.; Bertozzi, Carolyn R.

doi:10.1038/nrd1751

Cited by 1,493 publications

(1,245 citation statements)

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“…Changes in glycosylation not only include over and under expression of naturally occurring carbohydrates/glycans but also newly expressed glycans that are specific to embryonic cells (Dube, 2005). These changes are due to changes in enzyme levels in the Golgi apparatus and affect the core structure of the either N-linked and O-linked proteoglycans causing alterations of the terminal structure that is correlated with malignancy (Dube, 2005).…”

Section: Carbohydratesmentioning

confidence: 99%

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Involvement of l(–)-rhamnose in sea urchin gastrulation: a live embryo assay

Smith

Oppenheimer

2013

Zygote

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SummaryThe sea urchin embryo is a National Institutes of Health model system that has provided major developments, and is important in human health and disease. To obtain initial insights to identify glycans that mediate cellular interactions, Lytechinus pictus sea urchin embryos were incubated at 24 or 30 h post-fertilization with 0.0009–0.03 M alpha-cyclodextrin, melibiose, l(–)-rhamnose, trehalose, d(+)-xylose or l(–)-xylose in lower-calcium artificial sea water (pH 8.0, 15°C), which speeds the entry of molecules into the interior of the embryos. While α-cyclodextrin killed the embryos, and l(–)-xylose had small effects at one concentration tested, l(–)-rhamnose caused substantially increased numbers of unattached archenterons and exogastrulated embryos at low glycan concentrations after 18–24 h incubation with the sugar. The results were statistically significant compared with the control embryos in the absence of sugar (P < 0.05). The other sugars (melibiose, trehalose, d(+)-xylose) had no statistically significant effects whatsoever at any of the concentrations tested. In total, in the current study, 39,369 embryos were examined. This study is the first demonstration that uses a live embryo assay for a likely role for l(–)-rhamnose in sea urchin gastrula cellular interactions, which have interested investigators for over a century.

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Section: Carbohydratesmentioning

confidence: 99%

“…These changes are due to changes in enzyme levels in the Golgi apparatus and affect the core structure of the either N-linked and O-linked proteoglycans causing alterations of the terminal structure that is correlated with malignancy (Dube, 2005).…”

Section: Carbohydratesmentioning

confidence: 99%

Involvement of l(–)-rhamnose in sea urchin gastrulation: a live embryo assay

Smith

Oppenheimer

2013

Zygote

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“…Given the critical role of protein N-glycosylation in tumorigenesis and diagnosis 45,46 , the structure may serve as a platform for the development of small-molecule inhibitors targeting the N-glycosylation-related diseases in humans.…”

Section: Introductionmentioning

confidence: 99%

The atomic structure of a eukaryotic oligosaccharyltransferase complex

Bai

Wang

Zhao

et al. 2018

Nature

102

131

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SUMMARY N-glycosylation is a ubiquitous modification of eukaryotic secretory and membrane-bound proteins; about 90% of glycoproteins are N-glycosylated. The reaction is catalyzed by an eight-protein oligosaccharyltransferase complex, OST, embedded in the ER membrane. Our understanding of eukaryotic protein N-glycosylation has been limited due to the lack of high-resolution structures. Here we report a 3.5-Å resolution cryo-EM structure of the Saccharomyces cerevisiae OST, revealing the structures of Ost1–5, Stt3, Wbp1, and Swp1. We found that seven phospholipids mediate many of the inter-subunit interactions, and an Stt3 N-glycan mediates interaction with Wbp1 and Swp1 in the lumen. Ost3 was found to mediate the OST-Sec61 translocon interface, funneling the acceptor peptide towards the OST catalytic site as the nascent peptide emerges from the translocon. The structure provides novel insights into co-translational protein N-glycosylation and may facilitate the development of small-molecule inhibitors targeting this process.

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“…1 In this context, changes in cell surface glycosylation influence the way cancer cells interact with the extracellular matrix, neighbouring cells and the epithelium of the target organ, during metastatic invasion. [1][2][3] One of the key players in cancer progression is thought to be the monosaccharide sialic acid, which caps the end of Oand N-linked glycoproteins. 1 Certain sialyltransferases are overexpressed in colorectal and breast cancers, increasing the total content of sialic acid on the cell surface.…”

Section: Introductionmentioning

confidence: 99%

“…7 Studying glycosylation remains challenging due to the complexity of the glycome. 2 Metabolic glycan labelling has been a powerful tool for labelling cell surface glycans in vitro and in vivo. [7][8][9][10][11] In this method, cells are fed with a non-natural monosaccharide carrying a small, inert chemical reporter group.…”

Section: Introductionmentioning

confidence: 99%