Tenascin-C: Form versus function

Giblin, Sean Patrick; Midwood, Kim S.

doi:10.4161/19336918.2014.987587

Cited by 188 publications

(247 citation statements)

References 232 publications

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“…Finally, tenascin-C can be cleaved by matrix metalloproteases (MMPs) (Giblin and Midwood, 2015) and gingipain cysteine proteases (Ruggiero et al, 2013), which contributes to tenascin-C turnover in tissue. In vitro cleavage of purified tenascin-C through MMP-1,-2, -3 and -7 demonstrated that the majority of cleavage sites are located within the alternatively spliced domains, although MMP-7 and the proteinase ADAMTS5 (a disintegrin and metalloproteinase with thrombospondin motifs 5) both also cleave within the assembly domain.…”

Section: Box 1 the Evolution Of Tenascin-cmentioning

confidence: 99%

“…One study reports that glycosylated tenascin-C promotes proliferation of murine neuronal stem cells (Yagi et al, 2010). However, this modification is also expected to regulate the binding capabilities of tenascin-C, confer protection from proteolytic cleavage and/or interfere with hexamer assembly (Giblin and Midwood, 2015). Tenascin-C can also be modified posttranslationally through citrullination, where a positively charged arginine residue is converted into a neutral citrulline residue.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, new binding sites can be created that exist only across the boundaries of specific FNIII repeats. Splicing of tenascin-C can be extraordinarily dynamic, and has been best studied during development and in cancer, where the temporal and spatial expression of different isoforms is used to direct distinct cellular processes that drive embryogenesis and tumorigenesis (Giblin and Midwood, 2015).…”

Section: Introductionmentioning

confidence: 99%

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Tenascin-C at a glance

Midwood

Chiquet

Tucker

et al. 2016

Journal of Cell Science

333

357

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Tenascin-C (TNC) is a hexameric, multimodular extracellular matrix protein with several molecular forms that are created through alternative splicing and protein modifications. It is highly conserved amongst vertebrates, and molecular phylogeny indicates that it evolved before fibronectin. Tenascin-C has many extracellular binding partners, including matrix components, soluble factors and pathogens; it also influences cell phenotype directly through interactions with cell surface receptors. Tenascin-C protein synthesis is tightly regulated, with widespread protein distribution in embryonic tissues, but restricted distribution of tenascin-C in adult tissues. Tenascin-C is also expressed de novo during wound healing or in pathological conditions, including chronic inflammation and cancer. First described as a modulator of cell adhesion, tenascin-C also directs a plethora of cell signaling and gene expression programs by shaping mechanical and biochemical cues within the cellular microenvironment. Exploitment of the pathological expression and function of tenascin-C is emerging as a promising strategy to develop new diagnostic, therapeutic and bioengineering tools. In this Cell Science at a Glance article and the accompanying poster we provide a succinct and comprehensive overview of the structural and functional features of tenascin-C and its potential roles in developing embryos and under pathological conditions.

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Section: Box 1 the Evolution Of Tenascin-cmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Tenascin-C at a glance

Midwood

Chiquet

Tucker

et al. 2016

Journal of Cell Science

333

357

View full text Add to dashboard Cite

show abstract

“…Physiologically, there is strong evidence that the expression of alternative TNC splice variants is developmentally regulated and tissue-specific (89). Furthermore, RNA seq data from the Illumina Body Map project suggests that the long TNC-001 variant is detected in lung, colon and lymph tissues, while the short TNC-012 variant is detected in breast, ovary and prostate tissue (accessed via ENSEMBL, March 2016).…”

Section: Tenascin-c Splice Variants As Therapeutic Targetsmentioning

confidence: 99%

“…Similarly, antibodies with high affinity for the spliced region detected strong expression of large TNC variants in high grade astrocytomas, particularly near vascular structures and proliferating cells (99). There is currently widespread interest in using the tumour specific expression of TNC variants to target anti-cancer therapies, and growing interest in developing variantspecific TNC antagonists (89).…”

Section: Tenascin-c Splice Variants As Therapeutic Targetsmentioning

confidence: 99%

Embracing the complexity of matricellular proteins: the functional and clinical significance of splice variation

Viloria

Hill

2016

Biomolecular Concepts

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Matricellular proteins influence wide-ranging fundamental cellular processes including cell adhesion, migration, growth and differentiation. They achieve this both through interactions with cell surface receptors and regulation of the matrix environment. Many matricellular proteins are also associated with diverse clinical disorders including cancer and diabetes. Alternative splicing is a precisely regulated process that can produce multiple isoforms with variable functions from a single gene. To date, the expression of alternate transcripts for the matricellular family has been reported for only a handful of genes. Here we analyse the evidence for alternative splicing across the matricellular family including the secreted protein acidic and rich in cysteine (SPARC), thrombospondin, tenascin and CCN families. We find that matricellular proteins have double the average number of splice variants per gene, and discuss the types of domain affected by splicing in matricellular proteins. We also review the clinical significance of alternative splicing for three specific matricellular proteins that have been relatively well characterised: osteopontin (OPN), tenascin-C (TNC) and periostin. Embracing the complexity of matricellular splice variants will be important for understanding the sometimes contradictory function of these powerful regulatory proteins, and for their effective clinical application as biomarkers and therapeutic targets.

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Glycomaterials to Investigate the Functional Role of Aberrant Glycosylation in Glioblastoma

Tondepu

Karumbaiah

2021

Adv Healthcare Materials

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Glioblastoma (GBM) is a stage IV astrocytoma that carries a dismal survival rate of ≈10 months postdiagnosis and treatment. The highly invasive capacity of GBM and its ability to escape therapeutic challenges are key factors contributing to the poor overall survival rate. While current treatments aim to target the cancer cell itself, they fail to consider the significant role that the GBM tumor microenvironment (TME) plays in promoting tumor progression and therapeutic resistance. The GBM tumor glycocalyx and glycan-rich extracellular matrix (ECM), which are important constituents of the TME have received little attention as therapeutic targets. A wide array of aberrantly modified glycans in the GBM TME mediate tumor growth, invasion, therapeutic resistance, and immunosuppression. Here, an overview of the landscape of aberrant glycan modifications in GBM is provided, and the design and utility of 3D glycomaterials are discussed as a tool to evaluate glycan-mediated GBM progression and therapeutic efficacy. The development of alternative strategies to target glycans in the TME can potentially unveil broader mechanisms of restricting tumor growth and enhancing the efficacy of tumor-targeting therapeutics.

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Tenascin-C: Form versus function

Cited by 188 publications

References 232 publications

Tenascin-C at a glance

Tenascin-C at a glance

Embracing the complexity of matricellular proteins: the functional and clinical significance of splice variation

Glycomaterials to Investigate the Functional Role of Aberrant Glycosylation in Glioblastoma

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