The extracellular matrix in development

Background Gastric cancer (GC) metastasis determines the prognosis of patients, and exploring the molecular mechanism of GC metastasis is expected to provide a theoretical basis for clinical treatment. Recent studies have shown that extracellular matrix protein is closely related to GC metastasis. This study aimed to explore the expression profile and role of COL5A2 (Collagen V-type α2), as an extracellular matrix protein, in GC. Methods The expression, overall survival and progression-free survival data of COL5 family members were extracted from The Cancer Genome Atlas(TCGA)database, respectively. Paraffin immunohistochemistry and RT-qPCR in GC and matched normal tissues were used to analyze the expression of the target genes. Weighted gene co-expression network analysis of the GSE62229 database was performed out to identify modules and associated genes, and the functions were predicted by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Results COL5A2 was selected as our research target in the TCGA database, and was also verified in the GSE62229 and GSE15459 datasets. COL5A2 was upregulated in GC tissues by paraffin immunohistochemistry and RT-qPCR. The analysis of clinicopathological characteristics showed a significant difference in the Borrmann type (P = 0.036), histological type (P = 0.013) and T stage(P = 0.011). The prognosis of patients with low COL5A2 expression was better than that of patients with high COL5A2 expression. GSEA results showed that the TCGA and GSE62229 samples were significantly enriched in several well-known cancer-related pathways, such as the TGF-β, MAPK, and JAK2 signaling pathways. Conclusion COL5A2 was most closely related to advanced GC among COL5 family members. High COL5A2 expression is associated with a poor prognosis in GC, and may be a novel therapeutic target for GC.

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“…Collagen is the main component of the extracellular matrix (ECM), which can be divided into types I-V [5].…”

Section: Introductionmentioning

confidence: 99%

The TCGA and GEO databases identify COL5A2 as a poorly prognostic gene in patients with advanced gastric cancer

Tan

Chen

Xing

et al. 2020

Preprint

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“…The extracellular matrix (ECM) is a complex scaffold made of hundreds of proteins that instructs cell behaviors, organizes tissue architecture, and regulates organ function (1). It plays prominent roles during embryonic development, aging, and diseases (2)(3)(4)(5)(6)(7). Mechanistically, ECM proteins can play these roles through their interactions with each other, with growth factors or morphogens, and with receptors present at the cell surface (1,8,9).…”

Section: Introductionmentioning

confidence: 99%

Computational and experimental characterization of the novel ECM glycoprotein SNED1 and prediction of its interactome

Vallet

Davis

Barqué

et al. 2020

Preprint

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The extracellular matrix (ECM) protein SNED1 has been shown to promote breast cancer metastasis and control neural crest cell-specific craniofacial development, but the cellular and molecular mechanisms by which it does so remain unknown. ECM proteins exert their functions by binding to cell surface receptors, sequestering growth factors, and interacting with other ECM proteins, actions that can be predicted using knowledge of protein’s sequence, structure and post-translational modifications. Here, we combined in-silico and in-vitro approaches to characterize the physico-chemical properties of SNED1 and infer its putative functions. To do so, we established a mammalian cell system to produce and purify SNED1 and its N-terminal fragment, which contains a NIDO domain. We have determined experimentally SNED1’s potential to be glycosylated, phosphorylated, and incorporated into insoluble ECM produced by cells. In addition, we used biophysical and computational methods to determine the secondary and tertiary structures of SNED1 and its N-terminal fragment. The tentative ab-initio model we built of SNED1 suggests that it is an elongated protein presumably able to bind multiple partners. Using computational predictions, we identified 114 proteins as putative SNED1 interactors. Pathway analysis of the newly-predicted SNED1 interactome further revealed that binding partners of SNED1 contribute to signaling through cell surface receptors, such as integrins, and participate in the regulation of ECM organization and developmental processes. Altogether, we provide a wealth of information on an understudied yet important ECM protein with the potential to decipher its functions in physiology and diseases.

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“…However, ESC culture practices are still antiquated, relying on adherence to two-dimensional (2-D) tissue-culture polystyrene plates often coated with natural or synthetic substrates mimicking extracellular matrix (ECM) components for the propagation of cells [6]. Generally, 2-D culture conditions fail to mimic the native three-dimensional (3-D) microenvironments that are responsible for the regulation of cell fate in vivo, allowing for dynamic spatial interactions between cells, ECM components, and gradients of soluble factors via biochemical, mechanical, and structural stimuli [23][24][25]. 2-D culture fails to accurately reproduce the physiology of the embryo [26] resulting in the spontaneous differentiation of ESC colonies in vitro [27,28].…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic analysis of naïve human embryonic stem cells cultured in three-dimensional PEG scaffolds

McKee

Brown

Bakshi

et al. 2020

Preprint

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Derivation of primed and naïve human embryonic stem cells (ESCs) have prompted an increased interest in devising culture conditions for maintaining their pluripotency and differential potential. Naïve ESCs are characterized by improved viability, proliferation, and differentiation capacity in comparison to primed ESCs. However, traditional two-dimensional (2-D) cell culture techniques fail to mimic the three-dimensional (3-D) in vivo microenvironment, which results in altered morphological and molecular characteristics of ESCs. Here, we describe the use of 3-D self-assembling scaffolds that support growth and maintenance of the naïve state characteristics of human ESC line, Elf1. Scaffolds were formed via a Michael addition reaction upon combination of two 8-arm polyethylene glycol (PEG) polymers functionalized with thiol (PEG-8-SH) and acrylate (PEG-8-Acr) end groups. 3-D scaffolds not only maintained the naïve state, but also supported long-term growth for up to 3 weeks without requiring routine passaging and manipulation. 3-D grown cells exhibited upregulation of core (OCT4, NANOG, and SOX2) and naïve (KLF17, KLF4, TFCP2L1, DPPA3, and DNMT3L) genes. These genes returned to normal levels when 3-D grown cells were propagated under 2-D culture conditions. Examination of RNA-sequencing demonstrated significant changes in gene expression profiles between 2-D and 3-D grown Elf1 cells. Gene Ontology analysis revealed upregulation of biological processes involved in the regulation of transcription and translation, as well as β-catenin-TCF complex assembly, extracellular matrix organization, and chromatin remodeling in 3-D grown Elf1 cells. 3-D culture conditions also induced upregulation of genes associated with several signaling pathways including Wnt signaling and focal adhesion. However, p53 signaling pathway associated genes were downregulated under these culture conditions. Our findings provide insight into the possible mechanisms of prolonged self-renewal as well as upregulation of pluripotent genes stimulated by the transduction of mechanical signals from the 3-D microenvironment.

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The extracellular matrix in development

Cited by 288 publications

References 286 publications

The TCGA and GEO databases identify COL5A2 as a poorly prognostic gene in patients with advanced gastric cancer

The TCGA and GEO databases identify COL5A2 as a poorly prognostic gene in patients with advanced gastric cancer

Computational and experimental characterization of the novel ECM glycoprotein SNED1 and prediction of its interactome

Transcriptomic analysis of naïve human embryonic stem cells cultured in three-dimensional PEG scaffolds

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