Fibronectin in cell adhesion and migration via N-glycosylation

Hsiao, Cheng Te; Cheng, Hung Wei; Huang, Chi Ming; Li, Hao Ru; Ou, Meng Hsin; Huang, Jie Rong; Khoo, Kay‐Hooi; Yu, Helen; Chen, Yin-Quan; Wang, Yang Kao; Chiou, Arthur; Kuo, Jean Cheng

doi:10.18632/oncotarget.19969

Cited by 115 publications

(84 citation statements)

References 50 publications

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“…Previous reports have shown that N-glycosylation negatively impacts platelet adhesion to VWF in the absence of collagen, 30 however, our data indicates a positive role for N-glycans in VWF adhesion to collagen, at least under non-shear conditions. Consistent with previous studies, 31 32 we found FN1-collagen binding was positively influenced by Nglycosylation, and binding by FN1 to collagen dropped more than 2-fold following PNGase F treatment. In agreement with previous studies, 33 34 we found the PPI between vitronectin (VTN) and collagen to be enhanced 2.2-fold following sialidase treatment (Fig.…”

Section: Major Platelet Adhesive Receptors and Proteins Require N-glysupporting

confidence: 92%

Deciphering the roles of N-glycans on collagen-platelet interactions

Toonstra¹,

Hu²,

Zhang³

2018

Preprint

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Collagen is a potent agonist for platelet activation, presenting itself as a key contributor to coagulation via interactions with platelet glycoproteins. The fine-details dictating plateletcollagen interactions are poorly understood. In particular, glycosylation could be a key determinant in the platelet-collagen interaction. Here we report an affinity purification coupled to mass spectrometry-based approach to elucidate the function of N-glycans in dictating plateletcollagen interactions. By integrative proteomic and glycoproteomic analysis of collagen-platelet interactive proteins with N-glycan manipulation, we demonstrate that the interaction of platelet adhesive receptors with collagen are highly N-glycan regulated, with glycans on many receptors playing positive roles on collagen binding, with glycans on other platelet glycoproteins exhibiting inhibitory roles on the binding to collagen. Our results significantly enhance our understanding of the details of glycans influencing the platelet-collagen interaction.3 Platelets are crucial mediators of primary hemostasis and endothelial repair, however, chronic pathological platelet activation also plays a critical role in progressive vascular occlusion diseases. 1 Blood vessel damage exposes collagen within the subendothelial surface which serves as the primary target site of platelet action. 1 Contact between platelet receptor proteins and nascent exposed collagen instigates platelet activation and initiates the coagulation cascade. The coagulation cascade is well defined, however, a detailed understanding of fine details dictating the platelet-collagen interaction remains elusive. Post-translational modifications, including protein glycosylation are potential key regulators of protein-protein interactions, and have been shown to contribute to platelet protein adhesion to collagen. 2 3 The majority of critical collagen binding platelet membrane proteins, including GPIbα, GPIIb/IIIa, CD36, GPVI, and GPIX, are glycoproteins. Previous studies have reported the significant impact glycosylation on plateletcollagen adhesion for both N-glycosylation (glycoprotein VI (GPVI), integrin β1 (ITGB1)), 4 5 and O-glycosylation (glycoprotein Ib α (GP1BA), integrin αIIb, integrin α5 (ITGA5), and GPVI). 6 7 8 In addition, to other mechanisms, N-and O-glycosylation have been shown to play critical roles in many facets of the hemostatic system, including, expression, liver clearance 9 10 11 12 13 14 , catalytic activity, 15 signal transduction, 16 as well as the proper function of von Willebrand factor (VWF) in the clotting process. 15 17 18 19 20 21 However, there is a conspicuous dearth of information regarding the specific role of N-glycosylation dictating the binding of platelet proteins to collagen. Studies that have analyzed the impact of glycosylation on particular platelet protein function have relied predominantly on recombinant techniques for protein expression. The glycosylation of recombinant proteins varies widely based on cell type that is used to generate the proteins...

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Section: Major Platelet Adhesive Receptors and Proteins Require N-glysupporting

confidence: 92%

Deciphering the roles of N-glycans on collagen-platelet interactions

Toonstra¹,

Hu²,

Zhang³

2018

Preprint

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“…In clear cell RCC, upregulation of protein glycosylation in cancer cells may be useful in diagnosis and determining disease prognosis . Furthermore, N‐glycosylation is involved in cell adhesion and is associated with reduced expression of E‐cadherin, which modulates the metastatic potential of cancer cells . We hypothesize that this pathway might contribute to cancer pathogenesis such that upregulation of PMM2 might enhance cancer cell aggressiveness by increased N‐glycosylation.…”

Section: Discussionmentioning

confidence: 98%

Impact of novel oncogenic pathways regulated by antitumor miR‐451a in renal cell carcinoma

et al. 2018

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Recent analyses of our microRNA (miRNA) expression signatures obtained from several types of cancer have provided novel information on their molecular pathology. In renal cell carcinoma (RCC), expression of microRNA‐451a (miR‐451a) was significantly downregulated in patient specimens and low expression of miR‐451a was significantly associated with poor prognosis of RCC patients (P = .00305) based on data in The Cancer Genome Atlas. The aims of the present study were to investigate the antitumor roles of miR‐451a and to identify novel oncogenic networks it regulated in RCC cells. Ectopic expression of miR‐451a significantly inhibited cancer cell migration and invasion by RCC cell lines, suggesting that miR‐451a had antitumor roles. To identify oncogenes regulated by miR‐451a in RCC cells, we analyzed genome‐wide gene expression data and examined information in in silico databases. A total of 16 oncogenes and were found to be possible targets of miR‐451a regulation. Interestingly, high expression of 9 genes (PMM2,CRELD2,CLEC2D,SPC25,BST2,EVL,TBX15,DPYSL3, and NAMPT) was significantly associated with poor prognosis. In this study, we focused on phosphomannomutase 2 (PMM2), which was the most strongly associated with prognosis. Overexpression of PMM2 was detected in clinical specimens and Spearman's rank test indicated a negative correlation between the expression levels of miR‐451a and PMM2 (P = .0409). Knockdown of PMM2 in RCC cells inhibited cancer cell migration and invasion, indicating overexpression of PMM2 could promote malignancy. Analytic strategies based on antitumor miRNAs is an effective tool for identification of novel pathways of cancer.

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“…CAMs are grouped into several families, namely, immunoglobulins, cadherins, integrins, selectins and ECM proteins (Table 1). 38,39,48,[40][41][42][43][44][45][46][47] These proteins can mediate cell adhesion by heterophilic (between cells of a different type) and homophilic (between cells of a single type) interactions. CAMs have specific affinities for cell surface glycoproteins, helping the specific location of cells within the tissues and transport of biochemical information to coordinate homeostasis including signal transduction, cellular communication, and recognition.…”

Section: Cellular Recognition and Adhesion Peptidesmentioning

confidence: 99%