scholarly journals N-Glycoproteomic Profiling Reveals Alteration In Extracellular Matrix Organization In Non-Type Bladder Carcinoma

2019 ◽  
Vol 8 (9) ◽  
pp. 1303 ◽  
Author(s):  
Barnali Deb ◽  
Krishna Patel ◽  
Gajanan Sathe ◽  
Prashant Kumar
Keyword(s):  
Extracellular Matrix ◽  
Bladder Carcinoma ◽  
Molecular Subtype ◽  
Site Occupancy ◽  
Glycosylation Site ◽  
Protein Glycosylation ◽  
Protein Abundance ◽  
Cellular Functions ◽  
Cancer Subtypes ◽  
Matrix Organization

Treatment of advanced and metastatic bladder carcinoma is often ineffective and displays variable clinical outcomes. Studying this aggressive molecular subtype of bladder carcinoma will lead to better understanding of the pathogenesis which may lead to the identification of new therapeutic strategies. The non-type bladder subtype is phenotypically mesenchymal and has mesenchymal features with a high metastatic ability. Post-translational addition of oligosaccharide residues is an important modification that influences cellular functions and contributes to disease pathology. Here, we report the comparative analysis of N-linked glycosylation across bladder cancer subtypes. To analyze the glycosite-containing peptides, we carried out LC-MS/MS-based quantitative proteomic and glycoproteomic profiling. We identified 1299 unique N-linked glycopeptides corresponding to 460 proteins. Additionally, we identified 118 unique N-linked glycopeptides corresponding to 84 proteins to be differentially glycosylated only in non-type subtypes as compared to luminal/basal subtypes. Most of the altered glycoproteins were also observed with changes in their global protein expression levels. However, alterations in 55 differentially expressed glycoproteins showed no significant change at the protein abundance level, representing that the glycosylation site occupancy was changed between the non-type subtype and luminal/basal subtypes. Importantly, the extracellular matrix organization pathway was dysregulated in the non-type subtype of bladder carcinoma. N-glycosylation modifications in the extracellular matrix organization proteins may be a contributing factor for the mesenchymal aggressive phenotype in non-type subtype. These aberrant protein glycosylation would provide additional avenues to employ glycan-based therapies and may lead to the identification of novel therapeutic targets.

Quantitative N-glycoproteomics of milk fat globule membrane in human colostrum and mature milk reveals changes in protein glycosylation during lactation

2018 ◽  
Vol 9 (2) ◽  
pp. 1163-1172 ◽  
Author(s):  
Xueyan Cao ◽  
Shimo Kang ◽  
Mei Yang ◽  
Weixuan Li ◽  
Shangyi Wu ◽  
...  
Keyword(s):  
Milk Fat ◽  
Site Occupancy ◽  
Glycosylation Site ◽  
Protein Glycosylation ◽  
Mature Milk ◽  
Milk Fat Globule Membrane ◽  
Human Colostrum ◽  
Milk Fat Globule ◽  
Fat Globule ◽  
Glycosylation Site Occupancy

The present study profiled the N-glycoproteome and quantified the changes of N-glycosylation site occupancy of MFGM proteins during lactation.

scholarly journals Modulating Tumor Cell Functions by Tunable Nanopatterned Ligand Presentation

Nanomaterials ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 212
Author(s):  
Katharina Amschler ◽  
Michael P. Schön
Keyword(s):  
Extracellular Matrix ◽  
Tumor Cell ◽  
Cell Fate ◽  
Epithelial Mesenchymal Transition ◽  
Model Systems ◽  
Cellular Functions ◽  
Biophysical Parameters ◽  
Ligand Density ◽  
Mesenchymal Transition ◽  
Cell Functions

Cancer comprises a large group of complex diseases which arise from the misrouted interplay of mutated cells with other cells and the extracellular matrix. The extracellular matrix is a highly dynamic structure providing biochemical and biophysical cues that regulate tumor cell behavior. While the relevance of biochemical signals has been appreciated, the complex input of biophysical properties like the variation of ligand density and distribution is a relatively new field in cancer research. Nanotechnology has become a very promising tool to mimic the physiological dimension of biophysical signals and their positive (i.e., growth-promoting) and negative (i.e., anti-tumoral or cytotoxic) effects on cellular functions. Here, we review tumor-associated cellular functions such as proliferation, epithelial-mesenchymal transition (EMT), invasion, and phenotype switch that are regulated by biophysical parameters such as ligand density or substrate elasticity. We also address the question of how such factors exert inhibitory or even toxic effects upon tumor cells. We describe three principles of nanostructured model systems based on block copolymer nanolithography, electron beam lithography, and DNA origami that have contributed to our understanding of how biophysical signals direct cancer cell fate.

scholarly journals The Role of the Extracellular Matrix Components in Cutaneous Wound Healing

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Pawel Olczyk ◽  
Łukasz Mencner ◽  
Katarzyna Komosinska-Vassev
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Growth Factors ◽  
Wound Repair ◽  
Structural Integrity ◽  
Healing Process ◽  
Cellular Functions ◽  
Extracellular Matrix Components ◽  
Essential Components ◽  
Matrix Components

Wound healing is the physiologic response to tissue trauma proceeding as a complex pathway of biochemical reactions and cellular events, secreted growth factors, and cytokines. Extracellular matrix constituents are essential components of the wound repair phenomenon. Firstly, they create a provisional matrix, providing a structural integrity of matrix during each stage of healing process. Secondly, matrix molecules regulate cellular functions, mediate the cell-cell and cell-matrix interactions, and serve as a reservoir and modulator of cytokines and growth factors’ action. Currently known mechanisms, by which extracellular matrix components modulate each stage of the process of soft tissue remodeling after injury, have been discussed.

scholarly journals Planar cell polarity proteins differentially regulate extracellular matrix organization and assembly during zebrafish gastrulation

2013 ◽  
Vol 383 (1) ◽  
pp. 39-51 ◽  
Author(s):  
Michael R. Dohn ◽  
Nathan A. Mundell ◽  
Leah M. Sawyer ◽  
Julie A. Dunlap ◽  
Jason R. Jessen
Keyword(s):  
Extracellular Matrix ◽  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Matrix Organization ◽  
Polarity Proteins

scholarly journals Construction of Prognostic Prediction Model for Stomach Adenocarcinoma Based on the TCGA Database.

2020 ◽  
Author(s):  
Zhengzhong Gu ◽  
Xiaohan Cui ◽  
Xudong Wang
Keyword(s):  
Gastric Cancer ◽  
Extracellular Matrix ◽  
Protein Kinase ◽  
Network Analysis ◽  
Differentially Expressed Genes ◽  
Differentially Expressed ◽  
Stomach Adenocarcinoma ◽  
Matrix Organization ◽  
Prognostic Prediction ◽  
New Biomarkers

Abstract Background: Prognostic prediction models have been developed to detect new biomarkers of gastric cancer (GC). The identification of new biomarkers could provide theoretical foundations for the application of molecular targeted therapy in advanced GC. The aim of this study was to construct a prognostic prediction model for stomach adenocarcinoma (STAD) based on The Cancer Genome Atlas (TCGA) database. Methods: First, we used the "limma" package to screen differentially expressed genes (DEGs) based on TCGA database. Gene ontology (GO) analysis was performed using the "ClusterProfiler" package. The interactions between proteins and the relationships between differentially expressed genes and clinical features were analyzed by protein-protein interaction (PPI) network analysis and weighted gene coexpression network analysis (WGCNA), respectively. Then, gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were used to identify differentially enriched pathways. The GenVisR package and CIBERSORT were used to identify mutations and assess immune infiltration. Finally, the expression of COL3A1 in STAD tissues was verified by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting.Results: Six differentially expressed genes were screened out, namely, COL3A1, ADAMTS12, BGN, FNDC1, AEBP1 and HTRA3. The enrichment results showed that differentially expressed genes were involved in multiple pathways in STAD, such as those related to the extracellular matrix, extracellular structure organization, and extracellular matrix organization. The differentially expressed genes were related to immune infiltration via the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathways. The western blotting and RT-qPCR results suggested that COL3A1 was overexpressed in STAD tissues compared with normal tissues.Conclusion: COL3A1, ADAMTS12, BGN, FNDC1, AEBP1 and HTRA3 could play important roles in the tumorigenesis and progression of STAD via various pathways, including those involving the extracellular matrix, extracellular structure organization, and extracellular matrix organization. COL3A1, ADAMTS12, BGN, FNDC1, AEBP1, and HTRA3 act as oncogenes in most cancers and may be biomarkers. Additionally, the identification of COL3A1 as a candidate biomarker provides a direction for further research on the role of tumor immunity in gastric cancer.

scholarly journals Cancer metabolic subtypes and their association with molecular and clinical features

2021 ◽  
Author(s):  
Enrico Moiso ◽  
Paolo Provero
Keyword(s):  
Clinical Data ◽  
Large Scale ◽  
Tumor Grade ◽  
Point Of View ◽  
General Point ◽  
Protein Abundance ◽  
Phenotypic Data ◽  
Cancer Subtypes ◽  
Molecular Features

Alteration of metabolic pathways in cancer has been investigated for many years, beginning way before the discovery of the role of oncogenes and tumor suppressors, and the last few years have witnessed a renewed interest in this topic. Large-scale molecular and clinical data on tens of thousands of samples allow us today to tackle the problem from a general point of view. Here we show that trancriptomic profiles of tumors can be exploited to define metabolic cancer subtypes, that can be systematically investigated for association with other molecular and clinical data. We find thousands of significant associations between metabolic subtypes and molecular features such as somatic mutations, structural variants, epigenetic modifications, protein abundance and activation; and with clinical/phenotypic data including survival probability, tumor grade, and histological types. Our work provides a methodological framework and a rich database of statistical associations, accessible from https://metaminer.unito.it, that will contribute to the understanding of the role of metabolic alterations in cancer and to the development of precision therapeutic strategies.

scholarly journals Regulation of cellular functions by extracellular matrix.

1992 ◽  
Vol 2 (10) ◽  
pp. S83 ◽  
Author(s):  
A Teti
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor Receptor ◽  
Matrix Proteins ◽  
Intercellular Spaces ◽  
Cellular Functions ◽  
Proliferation And Differentiation ◽  
Alpha Beta ◽  
Covalently Linked ◽  
Multicellular Organisms ◽  
Specific Ligand

Multicellular organisms are formed by specialized cells assembled in tissues. Individual cells contact and interact with other cells and with the extracellular matrix--a network of secreted proteins and carbohydrates that fills the intercellular spaces. The extracellular matrix helps cells to bind together and regulates a number of cellular functions, such as adhesion, migration, proliferation, and differentiation. It is formed by macromolecules, locally secreted by resident cells. The two main classes of macromolecules are polysaccharide glycosaminoglycans, usually covalently linked to proteins in the form of proteoglycans, and fibrous proteins of two functional types, structural (collagen, elastin) and adhesive (fibronectin, laminin, vitronectin, etc.). Receptors for extracellular matrix macromolecules are present in virtually all of the cells studied. They belong to the superfamily of integrins, alpha beta heterodimers, which, in most cases, recognize the Arg-Gly-Asp sequence of extracellular matrix proteins. On the exterior side of the cell, integrins link an extracellular matrix macromolecule, whereas in the cytosol, they bind the cytoskeleton, thereby forming a membrane bridge between extracellular and intracellular fibers. This structure enables the cell to adhere to the substratum. Similar to hormone- or growth factor-receptor binding, the interaction of the integrin with its specific ligand induces immediate signal transduction and influences cellular activities.

scholarly journals Distance-dependent adhesion of vascular cells on biofunctionalized nanostructures

2017 ◽  
Vol 3 (2) ◽  
pp. 683-686
Author(s):  
Sarah Biela ◽  
Britta Striegl ◽  
Kerstin Frey ◽  
Joachim P. Spatz ◽  
Ralf Kemkemer
Keyword(s):  
Extracellular Matrix ◽  
Vascular Tissue ◽  
Cell Types ◽  
Cell Interaction ◽  
Vascular Cells ◽  
Cellular Functions ◽  
Ligand Interaction ◽  
Nanostructured Surfaces ◽  
Peptide Motifs ◽  
Cell Cell

AbstractCell-cell and cell-extracellular matrix (ECM) adhesion regulates fundamental cellular functions and is crucial for cell-material contact. Adhesion is influenced by many factors like affinity and specificity of the receptor-ligand interaction or overall ligand concentration and density. To investigate molecular details of cell-ECM and cadherins (cell-cell) interaction in vascular cells functional nanostructured surfaces were used Ligand-functionalized gold nanoparticles (AuNPs) with 6-8 nm diameter, are precisely immobilized on a surface and separated by non-adhesive regions so that individual integrins or cadherins can specifically interact with the ligands on the AuNPs. Using 40 nm and 90 nm distances between the AuNPs and functionalized either with peptide motifs of the extracellular matrix (RGD or REDV) or vascular endothelial-cadherins (VEC), the influence of distance and ligand specificity on spreading and adhesion of endothelial cells (ECs) and smooth muscle cells (SMCs) was investigated. We demonstrate that RGD-dependent adhesion of vascular cells is similar to other cell types and that the distance dependence for integrin binding to ECM-peptides is also valid for the REDV motif. VEC-ligands decrease adhesion significantly on the tested ligand distances. These results may be helpful for future improvements in vascular tissue engineering and for development of implant surfaces.

Genetic pathway analysis reveals a major role for extracellular matrix organization in inflammatory and neuropathic pain

Pain ◽  
2019 ◽  
Vol 160 (4) ◽  
pp. 932-944 ◽  
Author(s):  
Marc Parisien ◽  
Alexander Samoshkin ◽  
Shannon N. Tansley ◽  
Marjo H. Piltonen ◽  
Loren J. Martin ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Neuropathic Pain ◽  
Pathway Analysis ◽  
Genetic Pathway ◽  
Matrix Organization

scholarly journals Physical Stability Comparisons of IgG1-Fc Variants: Effects of N-Glycosylation Site Occupancy and Asp/Gln Residues at Site Asn 297

2014 ◽  
Vol 103 (6) ◽  
pp. 1613-1627 ◽  
Author(s):  
Mohammad A. Alsenaidy ◽  
Solomon Z. Okbazghi ◽  
Jae Hyun Kim ◽  
Sangeeta B. Joshi ◽  
C. Russell Middaugh ◽  
...  
Keyword(s):  
Physical Stability ◽  
Site Occupancy ◽  
Glycosylation Site ◽  
Glycosylation Site Occupancy
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