TISIDB

Summary
Symbol	CSPG4
Name	chondroitin sulfate proteoglycan 4
Aliases	MCSPG; MEL-CSPG; HMW-MAA; melanoma-associated chondroitin sulfate proteoglycan; chondroitin sulfate proteogl ......
Chromosomal Location	15q24.2
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 [ TOP ]
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 [ TOP ]
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 [ TOP ]
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

> KEGG and Reactome Pathway

[ TOP ]

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
Symbol	CSPG4
Name	chondroitin sulfate proteoglycan 4
Aliases	MCSPG; MEL-CSPG; HMW-MAA; melanoma-associated chondroitin sulfate proteoglycan; chondroitin sulfate proteogl ......
Chromosomal Location	15q24.2
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

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Literatures describing the relation between CSPG4 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
20852124	Triple-Negative Breast Carcinoma	Inhibit immunity	CSPG4-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.
29196603	Soft Tissue Sarcoma	Inhibit immunity	Inhibiting 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.
22893632	Malignant Mesothelioma	Inhibit immunity	CSPG4 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
Symbol	CSPG4
Name	chondroitin sulfate proteoglycan 4
Aliases	MCSPG; MEL-CSPG; HMW-MAA; melanoma-associated chondroitin sulfate proteoglycan; chondroitin sulfate proteogl ......
Chromosomal Location	15q24.2
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

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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
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	CSPG4
Name	chondroitin sulfate proteoglycan 4
Aliases	MCSPG; MEL-CSPG; HMW-MAA; melanoma-associated chondroitin sulfate proteoglycan; chondroitin sulfate proteogl ......
Chromosomal Location	15q24.2
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

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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
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	0.104	0.899
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.813	0.761
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.39	0.821
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.447	0.426
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.603	0.839
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.259	0.942
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.026	0.971
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.263	0.894
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.223	0.919
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.938	0.483
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	1.967	0.261
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.216	0.167

> Mutation difference between responders and non-responders

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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
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	21.4	5.9	15.5	0.304
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	30	33.3	-3.3	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	7.4	6.8	0.6	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	7.4	8.5	-1.1	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	11.8	-11.8	0.193
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	16.7	-16.7	0.429
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	9.1	-9.1	0.458
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	11.1	6.2	4.9	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	20	11.1	8.9	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	3.7	-1.1	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	0	4.5	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	7.1	-7.1	0.467
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	CSPG4
Name	chondroitin sulfate proteoglycan 4
Aliases	MCSPG; MEL-CSPG; HMW-MAA; melanoma-associated chondroitin sulfate proteoglycan; chondroitin sulfate proteogl ......
Chromosomal Location	15q24.2
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 [ TOP ]

Summary
Symbol	CSPG4
Name	chondroitin sulfate proteoglycan 4
Aliases	MCSPG; MEL-CSPG; HMW-MAA; melanoma-associated chondroitin sulfate proteoglycan; chondroitin sulfate proteogl ......
Chromosomal Location	15q24.2
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 [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CSPG4
Name	chondroitin sulfate proteoglycan 4
Aliases	MCSPG; MEL-CSPG; HMW-MAA; melanoma-associated chondroitin sulfate proteoglycan; chondroitin sulfate proteogl ......
Chromosomal Location	15q24.2
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 [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	CSPG4
Name	chondroitin sulfate proteoglycan 4
Aliases	MCSPG; MEL-CSPG; HMW-MAA; melanoma-associated chondroitin sulfate proteoglycan; chondroitin sulfate proteogl ......
Chromosomal Location	15q24.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CSPG4 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CSPG4
Name	chondroitin sulfate proteoglycan 4
Aliases	MCSPG; MEL-CSPG; HMW-MAA; melanoma-associated chondroitin sulfate proteoglycan; chondroitin sulfate proteogl ......
Chromosomal Location	15q24.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CSPG4 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CSPG4
Name	chondroitin sulfate proteoglycan 4
Aliases	MCSPG; MEL-CSPG; HMW-MAA; melanoma-associated chondroitin sulfate proteoglycan; chondroitin sulfate proteogl ......
Chromosomal Location	15q24.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CSPG4 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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