Functional roles of <scp>CSPG</scp>4/<scp>NG</scp>2 in chondrosarcoma

Jamil, N. S. M.; Azfer, Asim; Worrell, Harrison; Salter, Donald

doi:10.1111/iep.12189

Cited by 14 publications

(12 citation statements)

References 43 publications

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“…It became clear that the PG [hereafter referred to as NG2/ chondroitin sulfate PG 4 (CSPG4)] is a rather ubiquitous surface component of immature and/or highly dynamic cell phenotypes throughout the human body. Recent investigations also unveil that the PG becomes frequently upregulated upon neoplastic transformation in a variety of cancer types (18)(19)(20). NG2/CSPG4 is also known to be frequently modulated during progression of the tumors and to be abundantly expressed in highly aggressive cancer cell subsets, metastatic formations, and injured tissues (especially the CNS).…”

Section: Phylogenesis and Post-translational Traits Of Ng2/cspg4mentioning

confidence: 99%

Structural deciphering of the NG2/CSPG4 proteoglycan multifunctionality

et al. 2018

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The chondroitin sulfate proteoglycan 4 (CSPG4) gene encodes a transmembrane proteoglycan (PG) constituting the largest and most structurally complex macromolecule of the human surf aceome. Its transcript shows an extensive evolutionary conservation and, due to the elaborated intracellular processing of the translated protein, it generates an array of glycoforms with the potential to exert variant‐specific functions. CSPG4‐mediated molecular events are articulated through the interaction with more than 40 putative ligands and the concurrent involvement of the ectodomain and cytoplasmic tail. Alternating inside‐out and outside‐in signal transductions may thereby be elicited through a tight functional connection of the PG with the cytoskeleton and its regulators. The potential of CSPG4 to influence both types of signaling mechanisms is also asserted by its lateral mobility along the plasma membrane and its intersection with microdomain‐restricted internalization and endocytic trafficking. Owing to the multitude of molecular interplays that CSPG4 may engage, and thanks to a differential phosphorylation of its intracellular domain accounted by crosstalking signaling pathways, the PG stands out for its unique capability to affect numerous cellular phenomena, including those purporting pathologic conditions. We discuss here the progresses made in advancing our understanding about the structural‐functional bases for the ability of CSPG4 to widely impact on cell behavior, such as to highlight how its multivalency may be exploited to interfere with disease progression.—Tamburini, E., Dallatomasina, A., Quartararo, J., Cortelazzi, B., Mangieri, D., Lazzaretti, M., Perris, R. Structural deciphering of the NG2/CSPG4 proteoglycan multifunctionality. FASEB J. 33, 3112–3128 (2019). http://www.fasebj.org

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Section: Phylogenesis and Post-translational Traits Of Ng2/cspg4mentioning

confidence: 99%

Structural deciphering of the NG2/CSPG4 proteoglycan multifunctionality

et al. 2018

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“…Domain-specific NG2 functionality in chondroblasts has yet to be fully resolved. NG2 is expressed in limb growth-plate cartilage 23 , articular cartilage 24 and in chondrosarcomas 25 . In osteoarthritic chondrocytes, NG2 adhesion with type VI collagen is compromised 24,26 .…”

Section: Introductionmentioning

confidence: 99%

Neuron/Glial Antigen 2-Type VI Collagen Interactions During Murine Temporomandibular Joint Osteoarthritis

Yotsuya

Bertagna

Hasan

et al. 2019

Sci Rep

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The degeneration of articular cartilage underscores the clinical pathology of temporomandibular joint osteoarthritis (TMJ-OA) and is promoted through dysfunctional biochemical or biophysical signaling. Transduction of these signals has a multifaceted regulation that includes important cell-matrix derived interactions. The matrix encapsulating the cells of the mandibular condylar cartilage (MCC) is rich in type VI collagen. Neuron/glia antigen 2 (NG2) is a type I transmembrane proteoglycan that binds with type VI collagen. This study defines the temporospatial dynamics of NG2-type VI collagen interactions during the progression of TMJ-OA. Membrane-bound NG2 is found to colocalize with pericellular type VI collagen in superficial layer cells in the MCC perichondrium but is present at high levels in the cytosol of chondroblastic and hypertrophic cells. When TMJ -OA is induced using a surgical instability model, localized disruptions of pericellular type VI collagen are observed on the central and medial MCC and are associated with significantly higher levels of cytosolic NG2. NG2 localized within the cytosol is found to be transported through clathrin and dynamin mediated endocytic pathways. These findings are consistent with NG2 behavior in other injury models and underscore the potential of NG2 as an entirely novel molecular mechanism of chondrocyte function contextually linked with TMJ-OA.

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“…The neural progenitor marker neuron-glial antigen 2 (NG2) is a well-known, promising molecular target in oncology. NG2, also known as chondroitin sulphate proteoglycan 4 (CSPG4), is a 300-kDa transmembrane chondroitin sulphate proteoglycan encoded by the CSPG4 gene on chromosome 15 (Jamil, Azfer, Worrell, & Salter, 2016;Stallcup, 2002); CSPG4 is aberrantly expressed in a wide variety of tumour types, such as melanomas, mesotheliomas, and breast and brain tumours, in which it correlates with tumour cell survival and proliferation (Amoury et al, 2016;Midwood & Salter, 1998). The role of CSPG4/NG2 in promoting angiogenesis, tumour infiltration, and growth warrants study to investigate its potential as a target for cancer treatment (Brehm et al, 2014;Nicolosi, Dallatomasina, & Perris, 2015).…”

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confidence: 99%

Furanodienone overcomes temozolomide resistance in glioblastoma through the downregulation of CSPG4‐Akt‐ERK signalling by inhibiting EGR1‐dependent transcription

Chen

Liu

Zheng

et al. 2019

Phytotherapy Research

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Glioblastoma multiforme (GBM) is a highly aggressive type of brain tumour. Patients with GBM respond poorly to chemotherapy and have poor survival outcomes. Neuron‐glial antigen 2 (NG2), also known as chondroitin sulphate proteoglycan 4 (CSPG4), has been shown to contribute to critical processes, such as cell survival, proliferation, and chemotherapy resistance, during glioma progression. In this study, we found that furanodienone (FUR), a diene‐type sesquiterpene isolated from the rhizomes of Rhizoma curcumae, exhibited a potential cytotoxic effect on temozolomide (TMZ)–resistant GBM cells in vitro by inhibiting CSPG4 and related signalling pathways. Studies investigating the mechanism demonstrated that FUR suppressed CSPG4‐Akt‐ERK signalling, inflammatory responses, and cytokine levels but activated caspase‐dependent pathways and mitochondrial dysfunction. Furthermore, an immunofluorescence assay and a dual‐luciferase reporter assay revealed that inhibition of EGR1‐mediated transcription might have contributed to the FUR‐dependent blockade of CSPG4 signalling and glioma cell survival. These results established a link between FUR‐induced CSPG4 inhibition and the suppression of EGR1‐dependent transcription. Attenuation of ERK1/2 and cytokine signalling might have generated the EGR1‐dependent negative feedback loop of the CSPG4 pathway during FUR‐induced apoptosis. These findings suggested that FUR could be a therapeutic candidate for the treatment of malignant glioma via targeting CSPG4 signalling.

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Functional roles of CSPG4/NG2 in chondrosarcoma

Cited by 14 publications

References 43 publications

Structural deciphering of the NG2/CSPG4 proteoglycan multifunctionality

Structural deciphering of the NG2/CSPG4 proteoglycan multifunctionality

Neuron/Glial Antigen 2-Type VI Collagen Interactions During Murine Temporomandibular Joint Osteoarthritis

Furanodienone overcomes temozolomide resistance in glioblastoma through the downregulation of CSPG4‐Akt‐ERK signalling by inhibiting EGR1‐dependent transcription

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