Role of Cytokine-Induced Glycosylation Changes in Regulating Cell Interactions and Cell Signaling in Inflammatory Diseases and Cancer

Dewald, Justine H.; Colomb, Florent; Bobowski-Gerard, Marie; Groux-Degroote, Sophie; Delannoy, Philippe

doi:10.3390/cells5040043

Cited by 69 publications

(56 citation statements)

References 148 publications

(160 reference statements)

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“…There are two major findings of the present study: (i) Expression of the N-acetylglucosaminyltransferase GCNT2 and its product, I antigen, is strongly induced during EMT by EGF and bFGF treatment of colon cancer cells, and (ii) the miR-199 family plays a key role in this process. Cancer cells undergo drastic changes in the repertoire of their cell surface glycans during their tumorigenic progression, with concomitant changes in the cellular transcription program and post-transcriptional regulation [24][25][26][27][28][29][30][31]. Certain glycans that are frequently found in cancers can be utilized as diagnostic markers.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of miR‐199a/b‐5p is associated with GCNT2 induction upon epithelial–mesenchymal transition in colon cancer

Chao

Huang

et al. 2017

FEBS Letters

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β-1,6-N-acetylglucosaminyltransferase 2 (GCNT2), which encodes a key glycosyltransferase for blood group I antigen synthesis, is induced upon epithelial-mesenchymal transition (EMT). Our results indicate that GCNT2 is upregulated upon EMT induced with epidermal growth factor and basic FGF in cultured human colon cancer cells. GCNT2 knockdown or overexpression decreases or increases, respectively, malignancy-related characteristics of colon cancer cells and I antigen levels. MiR-199a/b-5p is markedly downregulated upon EMT in colon cancer cells. Here, we find that miR-199a/b-5p consistently regulates GCNT2 expression in reporter assays and that it binds directly to the GCNT2 3' untranslated region intracellularly in RNA-induced silencing complex-trap assays. Overexpression of miR-199a/b-5p decreases GCNT2 expression and suppresses I antigen production. Based on these findings, we propose that miR-199a/b-5p regulates GCNT2 and I antigen expression in colon cancer cells undergoing EMT.

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Section: Discussionmentioning

confidence: 99%

Downregulation of miR‐199a/b‐5p is associated with GCNT2 induction upon epithelial–mesenchymal transition in colon cancer

Chao

Huang

et al. 2017

FEBS Letters

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“…Pro-inflammatory cytokines have been reported to regulate the expression of glycosyltransferases involved in the biosynthesis of disease-associated glycans. In particular, TNF was found able to up-regulate ST3GAL4 in human lung increasing sLe x expression [105]. It is worth recalling that sLe antigens can be carried by a glycosphingolipid backbone, forming gangliosides.…”

Section: Plasma Carriers Of Slex or Sleamentioning

confidence: 99%

Selectin Ligands Sialyl-Lewis a and Sialyl-Lewis x in Gastrointestinal Cancers

Trinchera

Aronica

Dall’Olio

2017

Biology

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The tetrasaccharide structures Siaα2,3Galβ1,3(Fucα1,4)GlcNAc and Siaα2,3Galβ1,4(Fucα1,3)GlcNAc constitute the epitopes of the carbohydrate antigens sialyl-Lewis a (sLea) and sialyl-Lewis x (sLex), respectively, and are the minimal requirement for selectin binding to their counter-receptors. Interaction of sLex expressed on the cell surface of leucocytes with E-selectin on endothelial cells allows their arrest and promotes their extravasation. Similarly, the rolling of cancer cells ectopically expressing the selectin ligands on endothelial cells is potentially a crucial step favoring the metastatic process. In this review, we focus on the biosynthetic steps giving rise to selectin ligand expression in cell lines and native tissues of gastrointestinal origin, trying to understand whether and how they are deregulated in cancer. We also discuss the use of such molecules in the diagnosis of gastrointestinal cancers, particularly in light of recent data questioning the ability of colon cancers to express sLea and the possible use of circulating sLex in the early detection of pancreatic cancer. Finally, we reviewed the data dealing with the mechanisms that link selectin ligand expression in gastrointestinal cells to cancer malignancy. This promising research field seems to require additional data on native patient tissues to reach more definitive conclusions.

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“…[8][9][10] There is ample evidence that sialic acids are important bioinformatic molecules, which play pivotal roles in biological, pathological, and immunological processes through modifying glycoproteins and glycolipids on the cell surface, including nervous system embryogenesis, 11 cell-cell interactions, 12,13 signal transduction, 14 bacterial and viral infection, 15,16 etc In addition, sialic acids on cell membranes are closely related to tumor invasion and metastasis. [24][25][26] In fact, the increased sialylation and expressions of these sialyltransferases genes in cervical cancer were also reported. For example, ST6GAL1 regulates macrophage apoptosis by controlling the α2,6-sialylation of tumor necrosis factor receptor-1.…”

Section: Introductionmentioning

confidence: 99%

ST3GAL3, ST3GAL4, and ST3GAL6 differ in their regulation of biological functions via the specificities for the α2,3‐sialylation of target proteins

Isaji

Duan

et al. 2019

FASEB j.

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The α2,3‐sialylation of N‐glycans is considered important but complicated because the functions of the three β‐galactoside α2,3‐sialyltransferases, ST3GAL3, ST3GAL4, and ST3GAL6, could be compensating for one another. To distinguish their specific functions, we established each individual knockout (KO) cell line. Loss of either the ST3GAL3 or ST3GAL6 genes decreased cell proliferation and colony formation, as opposed to the effect in the ST3GAL4 KO cells. The phosphorylation levels of ERK and AKT were significantly suppressed in the ST3GAL6 KO and ST3GAL3 KO cells, respectively. The cell aggregations were clearly observed in the KO cells, particularly the ST3GAL3 KO and ST3GAL6 KO cells, and the expression levels of E‐cadherin and claudin‐1 were enhanced in both those cell lines, but were suppressed in the ST3GAL4 KO cells. Those alterations were reversed with an overexpression of each corresponding gene in rescued cells. Of particular interest, the α2,3‐sialylation levels of β1 integrin were clearly suppressed in the ST3GAL4 KO cells, but these were increased in the ST3GAL3 KO and ST3GAL6 KO cells, whereas the α2,3‐sialylation levels of EGFR were significantly decreased in the ST3GAL6 KO cells. The decrease in α2,3‐sialylation increased the α2,6‐sialylation on β1, but not EGFR. Furthermore, a cross‐restoration of each of the three genes in ST3GAL6 KO cells showed that overexpression of ST3GAL6 sufficiently rescued the total α2,3‐sialylation levels, cell morphology, and α2,3‐sialylation of EGFR, whereas the α2,3‐sialylation levels of β1 were greatly enhanced by an overexpression of ST3GAL4. These results clearly demonstrate that the three α2,3‐sialyltransferases modify characteristic target proteins and regulate cell biological functions in different ways.

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Role of Cytokine-Induced Glycosylation Changes in Regulating Cell Interactions and Cell Signaling in Inflammatory Diseases and Cancer

Cited by 69 publications

References 148 publications

Downregulation of miR‐199a/b‐5p is associated with GCNT2 induction upon epithelial–mesenchymal transition in colon cancer

Downregulation of miR‐199a/b‐5p is associated with GCNT2 induction upon epithelial–mesenchymal transition in colon cancer

Selectin Ligands Sialyl-Lewis a and Sialyl-Lewis x in Gastrointestinal Cancers

ST3GAL3, ST3GAL4, and ST3GAL6 differ in their regulation of biological functions via the specificities for the α2,3‐sialylation of target proteins

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