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Browse CSPG4

Summary
SymbolCSPG4
Namechondroitin sulfate proteoglycan 4
Aliases MCSPG; MEL-CSPG; HMW-MAA; melanoma-associated chondroitin sulfate proteoglycan; chondroitin sulfate proteogl ......
Chromosomal Location15q24.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cell membrane Single-pass type I membrane protein Extracellular side Apical cell membrane Single-pass type I membrane protein Extracellular side Cell projection, lamellipodium membrane Single-pass type I membrane protein Extracellular side Cell surface Note=Localized at the apical plasma membrane it relocalizes to the lamellipodia of astrocytoma upon phosphorylation by PRKCA. Localizes to the retraction fibers. Localizes to the plasma membrane of oligodendrocytes (By similarity).
Domain PF00054 Laminin G domain
PF02210 Laminin G domain
Function

Proteoglycan playing a role in cell proliferation and migration which stimulates endothelial cells motility during microvascular morphogenesis. May also inhibit neurite outgrowth and growth cone collapse during axon regeneration. Cell surface receptor for collagen alpha 2(VI) which may confer cells ability to migrate on that substrate. Binds through its extracellular N-terminus growth factors, extracellular matrix proteases modulating their activity. May regulate MPP16-dependent degradation and invasion of type I collagen participating in melanoma cells invasion properties. May modulate the plasminogen system by enhancing plasminogen activation and inhibiting angiostatin. Functions also as a signal transducing protein by binding through its cytoplasmic C-terminus scaffolding and signaling proteins. May promote retraction fiber formation and cell polarization through Rho GTPase activation. May stimulate alpha-4, beta-1 integrin-mediated adhesion and spreading by recruiting and activating a signaling cascade through CDC42, ACK1 and BCAR1. May activate FAK and ERK1/ERK2 signaling cascades.

> Gene Ontology
 
Biological Process GO:0000187 activation of MAPK activity
GO:0001525 angiogenesis
GO:0006022 aminoglycan metabolic process
GO:0006023 aminoglycan biosynthetic process
GO:0006024 glycosaminoglycan biosynthetic process
GO:0006026 aminoglycan catabolic process
GO:0006027 glycosaminoglycan catabolic process
GO:0006029 proteoglycan metabolic process
GO:0006790 sulfur compound metabolic process
GO:0008347 glial cell migration
GO:0009100 glycoprotein metabolic process
GO:0009101 glycoprotein biosynthetic process
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0018212 peptidyl-tyrosine modification
GO:0030166 proteoglycan biosynthetic process
GO:0030203 glycosaminoglycan metabolic process
GO:0030204 chondroitin sulfate metabolic process
GO:0030205 dermatan sulfate metabolic process
GO:0030206 chondroitin sulfate biosynthetic process
GO:0030207 chondroitin sulfate catabolic process
GO:0030208 dermatan sulfate biosynthetic process
GO:0032147 activation of protein kinase activity
GO:0033674 positive regulation of kinase activity
GO:0042063 gliogenesis
GO:0043405 regulation of MAP kinase activity
GO:0043406 positive regulation of MAP kinase activity
GO:0043410 positive regulation of MAPK cascade
GO:0044272 sulfur compound biosynthetic process
GO:0044273 sulfur compound catabolic process
GO:0045860 positive regulation of protein kinase activity
GO:0048514 blood vessel morphogenesis
GO:0048771 tissue remodeling
GO:0050650 chondroitin sulfate proteoglycan biosynthetic process
GO:0050651 dermatan sulfate proteoglycan biosynthetic process
GO:0050654 chondroitin sulfate proteoglycan metabolic process
GO:0050655 dermatan sulfate proteoglycan metabolic process
GO:0050730 regulation of peptidyl-tyrosine phosphorylation
GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation
GO:0071900 regulation of protein serine/threonine kinase activity
GO:0071902 positive regulation of protein serine/threonine kinase activity
GO:1901136 carbohydrate derivative catabolic process
GO:1901565 organonitrogen compound catabolic process
GO:1903510 mucopolysaccharide metabolic process
Molecular Function -
Cellular Component GO:0005775 vacuolar lumen
GO:0005796 Golgi lumen
GO:0005924 cell-substrate adherens junction
GO:0005925 focal adhesion
GO:0016324 apical plasma membrane
GO:0030027 lamellipodium
GO:0030055 cell-substrate junction
GO:0031252 cell leading edge
GO:0031253 cell projection membrane
GO:0031256 leading edge membrane
GO:0031258 lamellipodium membrane
GO:0043202 lysosomal lumen
GO:0045177 apical part of cell
> KEGG and Reactome Pathway
 
KEGG -
Reactome R-HSA-1971475: A tetrasaccharide linker sequence is required for GAG synthesis
R-HSA-2024101: CS/DS degradation
R-HSA-2022870: Chondroitin sulfate biosynthesis
R-HSA-1793185: Chondroitin sulfate/dermatan sulfate metabolism
R-HSA-4420332: Defective B3GALT6 causes EDSP2 and SEMDJL1
R-HSA-3560801: Defective B3GAT3 causes JDSSDHD
R-HSA-3560783: Defective B4GALT7 causes EDS, progeroid type
R-HSA-3595174: Defective CHST14 causes EDS, musculocontractural type
R-HSA-3595172: Defective CHST3 causes SEDCJD
R-HSA-3595177: Defective CHSY1 causes TPBS
R-HSA-2022923: Dermatan sulfate biosynthesis
R-HSA-1643685: Disease
R-HSA-3560782: Diseases associated with glycosaminoglycan metabolism
R-HSA-3781865: Diseases of glycosylation
R-HSA-1630316: Glycosaminoglycan metabolism
R-HSA-1638091: Heparan sulfate/heparin (HS-GAG) metabolism
R-HSA-1430728: Metabolism
R-HSA-71387: Metabolism of carbohydrates
Summary
SymbolCSPG4
Namechondroitin sulfate proteoglycan 4
Aliases MCSPG; MEL-CSPG; HMW-MAA; melanoma-associated chondroitin sulfate proteoglycan; chondroitin sulfate proteogl ......
Chromosomal Location15q24.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between CSPG4 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between CSPG4 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
20852124Triple-Negative Breast CarcinomaInhibit immunityCSPG4-specific mAb 225.28 statistically significantly inhibited growth, adhesion, and migration of TNBC cells in vitro. mAb 225.28 induced 73.1% regression of tumor metastasis in a TNBC cell-derived experimental lung metastasis model (mAb 225.28 vs control, mean area of metastatic nodules = 44590.8 vs 165950.8 μm(2); difference of mean = 121360.0 μm(2), 95% confidence interval = 91010.7 to 151709.4 μm(2); P < .001). Additionally, mAb 225.28 statistically significantly reduced spontaneous lung metastases and tumor recurrences in an orthotopic xenograft mouse model. The mechanisms responsible for antitumor effect included increased apoptosis and reduced mitotic activity in tumor cells, decreased blood vessel density in the tumor microenvironment, and reduced activation of signaling pathways involved in cell survival, proliferation and metastasis.
29196603Soft Tissue SarcomaInhibit immunityInhibiting NG2/CSPG4 expression in established murine and human STSs decreased tumor volume by almost two-thirds and cell proliferation rate by 50%. NG2/CSPG4 antibody immunotherapy in human sarcomas established as xenografts in mice similarly decreased tumor volume, and expression of a lentivirus blocking NG2/CSPG4 expression inhibited tumor cell proliferation and increased the latency of engraftment. Gene profiling showed that Ng2/Cspg4 deletion altered the expression of genes regulating cell proliferation and apoptosis. Surprisingly, Ng2/Cspg4 deletion at the time of tumor initiation resulted in larger tumors. Gene expression profiling indicated substantial down-regulation of insulin-like growth factor binding protein (Igfbp) genes when Ng2/Cspg4 is depleted at tumor initiation, but not when Ng2/Cspg4 is depleted after tumor initiation.
22893632Malignant MesotheliomaInhibit immunityCSPG4 was expressed on 6 out of 8 MM cell lines and in 25 out of 41 MM biopsies, with minimal expression in surrounding healthy cells. MM cell adhesion was mediated by CSPG4-dependent engagement of ECM. Cell adhesion was inhibited by mAb TP41.2 resulting in decreased phosphorylation of focal adhesion kinase (FAK) and AKT, reduced expression of cyclin D1 and apoptosis.
Summary
SymbolCSPG4
Namechondroitin sulfate proteoglycan 4
Aliases MCSPG; MEL-CSPG; HMW-MAA; melanoma-associated chondroitin sulfate proteoglycan; chondroitin sulfate proteogl ......
Chromosomal Location15q24.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of CSPG4 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolCSPG4
Namechondroitin sulfate proteoglycan 4
Aliases MCSPG; MEL-CSPG; HMW-MAA; melanoma-associated chondroitin sulfate proteoglycan; chondroitin sulfate proteogl ......
Chromosomal Location15q24.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of CSPG4 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.1040.899
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.8130.761
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.390.821
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.4470.426
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.6030.839
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-0.2590.942
729033130MelanomaallAnti-PD-1 (nivolumab) 2623-0.0260.971
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 1511-0.2630.894
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.2230.919
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.9380.483
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.9670.261
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.2160.167
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of CSPG4 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 141721.45.915.50.304
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1033033.3-3.31
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27737.46.80.61
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27597.48.5-1.11
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)2117011.8-11.80.193
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)86016.7-16.70.429
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)131109.1-9.10.458
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91611.16.24.91
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 592011.18.91
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.63.7-1.11
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.504.51
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 161407.1-7.10.467
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolCSPG4
Namechondroitin sulfate proteoglycan 4
Aliases MCSPG; MEL-CSPG; HMW-MAA; melanoma-associated chondroitin sulfate proteoglycan; chondroitin sulfate proteogl ......
Chromosomal Location15q24.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CSPG4. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolCSPG4
Namechondroitin sulfate proteoglycan 4
Aliases MCSPG; MEL-CSPG; HMW-MAA; melanoma-associated chondroitin sulfate proteoglycan; chondroitin sulfate proteogl ......
Chromosomal Location15q24.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CSPG4. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CSPG4.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolCSPG4
Namechondroitin sulfate proteoglycan 4
Aliases MCSPG; MEL-CSPG; HMW-MAA; melanoma-associated chondroitin sulfate proteoglycan; chondroitin sulfate proteogl ......
Chromosomal Location15q24.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CSPG4. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolCSPG4
Namechondroitin sulfate proteoglycan 4
Aliases MCSPG; MEL-CSPG; HMW-MAA; melanoma-associated chondroitin sulfate proteoglycan; chondroitin sulfate proteogl ......
Chromosomal Location15q24.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of CSPG4 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolCSPG4
Namechondroitin sulfate proteoglycan 4
Aliases MCSPG; MEL-CSPG; HMW-MAA; melanoma-associated chondroitin sulfate proteoglycan; chondroitin sulfate proteogl ......
Chromosomal Location15q24.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between CSPG4 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolCSPG4
Namechondroitin sulfate proteoglycan 4
Aliases MCSPG; MEL-CSPG; HMW-MAA; melanoma-associated chondroitin sulfate proteoglycan; chondroitin sulfate proteogl ......
Chromosomal Location15q24.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting CSPG4 collected from DrugBank database.
> Drugs from DrugBank database
 

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