Tenascin-C Signaling in melanoma

Shao, Hanshuang; Kirkwood, John M.; Wells, Alan

doi:10.4161/19336918.2014.972781

Cited by 26 publications

(28 citation statements)

References 51 publications

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“…Here, Rho inhibition (through impairing syndecan-4 and integrin α5β1) and activation of Cdc42 and Rac (involving fascin) could be instrumental (reviewed in Lowy and Oskarsson, 2015). Tenascin-C can promote migration through epithelial-tomesenchymal-transition (EMT) and EGFR activation by the tenascin-C EGF-like repeats (reviewed in Lowy and Oskarsson, 2015;Shao et al, 2015). Finally, through regulating innate and adaptive immunity, tenascin-C can also contribute to tumor progression, although the mechanisms by which this occurs are not completely understood to date (Hauzenberger et al, 1999;Orend et al, 2014;Jachetti et al, 2015).…”

Section: Regulation Of Tnc Gene Expressionmentioning

confidence: 99%

Tenascin-C at a glance

Midwood

Chiquet

Tucker

et al. 2016

Journal of Cell Science

358

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: Regulation Of Tnc Gene Expressionmentioning

confidence: 99%

Tenascin-C at a glance

Midwood

Chiquet

Tucker

et al. 2016

Journal of Cell Science

358

357

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“…Nevertheless, it is also true that other mechanisms are critical regulators of resistance, such as the binding of tumor cells to these ECM components activating downstream pathways and triggering inhibition of drug-induced apoptosis and conferring increased resistance even to targeted therapeutics [ 82 , 83 , 84 ]. On top of these, the matricellular protein tenascin C also provides for survival by tonic signaling via the EGFR [ 86 ]. Furthermore, the stiffness of the matrix contributes to treatment resistance by hindering the diffusion of chemotherapeutic agents into cancer tissues via increased hydrostatic pressure [ 87 ].…”

Section: Mme and Metastatic Reactivationmentioning

confidence: 99%

A Perspective on Therapeutic Pan-Resistance in Metastatic Cancer

Korentzelos

Clark

Wells

2020

IJMS

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Metastatic spread represents the leading cause of disease-related mortality among cancer patients. Many cancer patients suffer from metastatic relapse years or even decades after radical surgery for the primary tumor. This clinical phenomenon is explained by the early dissemination of cancer cells followed by a long period of dormancy. Although dormancy could be viewed as a window of opportunity for therapeutic interventions, dormant disseminated cancer cells and micrometastases, as well as emergent outgrowing macrometastases, exhibit a generalized, innate resistance to chemotherapy and even immunotherapy. This therapeutic pan-resistance, on top of other adaptive responses to targeted agents such as acquired mutations and lineage plasticity, underpins the current difficulties in eradicating cancer. In the present review, we attempt to provide a framework to understand the underlying biology of this major issue.

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“…PRKCDBP, HLA-DRA2; McMahon et al, 2009;Whitmarsh, 2013), cell adhesion (e.g. Tenascin, Glypican-6; Shao et al, 2015), cell migration (e.g. Neuropilin 2, Tenascin, Glypican-6; Shao et al, 2015), angiogenesis (e.g.…”

Section: Validation Of the Resistance Signature By Transcriptomics Anmentioning

confidence: 99%

“…Tenascin, Glypican-6; Shao et al, 2015), cell migration (e.g. Neuropilin 2, Tenascin, Glypican-6; Shao et al, 2015), angiogenesis (e.g. Neuropilin 2), endosomal trafficking (e.g.…”

Section: Validation Of the Resistance Signature By Transcriptomics Anmentioning

confidence: 99%

Proteomic identification of a marker signature for MAPK i resistance in melanoma

et al. 2019

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MAPK inhibitors (MAPKi) show outstanding clinical response rates in melanoma patients harbouring BRAF mutations, but resistance is common. The ability of melanoma cells to switch from melanocytic to mesenchymal phenotypes appears to be associated with therapeutic resistance. High‐throughput, subcellular proteome analyses and RNAseq on two panels of primary melanoma cells that were either sensitive or resistant to MAPKi revealed that only 15 proteins were sufficient to distinguish between these phenotypes. The two proteins with the highest discriminatory power were PTRF and IGFBP7, which were both highly upregulated in the mesenchymal‐resistant cells. Proteomic analysis of CRISPR/Cas‐derived PTRF knockouts revealed targets involved in lysosomal activation, endocytosis, pH regulation, EMT, TGFβ signalling and cell migration and adhesion, as well as a significantly reduced invasive index and ability to form spheres in 3D culture. Overexpression of PTRF led to MAPKi resistance, increased cell adhesion and sphere formation. In addition, immunohistochemistry of patient samples showed that PTRF expression levels were a significant biomarker of poor progression‐free survival, and IGFBP7 levels in patient sera were shown to be higher after relapse.

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Tenascin-C Signaling in melanoma

Cited by 26 publications

References 51 publications

Tenascin-C at a glance

Tenascin-C at a glance

A Perspective on Therapeutic Pan-Resistance in Metastatic Cancer

Proteomic identification of a marker signature for MAPK i resistance in melanoma

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