TISIDB

Summary
Symbol	VCAM1
Name	vascular cell adhesion molecule 1
Aliases	CD106; INCAM-100; CD106 antigen; CD antigen CD106; VCAM-1; V-CAM 1; Vascular cell adhesion protein 1
Chromosomal Location	1p32-p31
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	Membrane; Single-pass type I membrane protein.
Domain	PF05790 Immunoglobulin C2-set domain PF07679 Immunoglobulin I-set domain PF00047 Immunoglobulin domain
Function	Important in cell-cell recognition. Appears to function in leukocyte-endothelial cell adhesion. Interacts with integrin alpha-4/beta-1 (ITGA4/ITGB1) on leukocytes, and mediates both adhesion and signal transduction. The VCAM1/ITGA4/ITGB1 interaction may play a pathophysiologic role both in immune responses and in leukocyte emigration to sites of inflammation.

> Gene Ontology [ TOP ]
Biological Process	GO:0001666 response to hypoxia GO:0002237 response to molecule of bacterial origin GO:0002521 leukocyte differentiation GO:0002526 acute inflammatory response GO:0002544 chronic inflammatory response GO:0002694 regulation of leukocyte activation GO:0002696 positive regulation of leukocyte activation GO:0007157 heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules GO:0007159 leukocyte cell-cell adhesion GO:0007160 cell-matrix adhesion GO:0007568 aging GO:0007584 response to nutrient GO:0009308 amine metabolic process GO:0009314 response to radiation GO:0009991 response to extracellular stimulus GO:0010035 response to inorganic substance GO:0010038 response to metal ion GO:0010043 response to zinc ion GO:0010212 response to ionizing radiation GO:0019722 calcium-mediated signaling GO:0019932 second-messenger-mediated signaling GO:0022406 membrane docking GO:0022407 regulation of cell-cell adhesion GO:0022409 positive regulation of cell-cell adhesion GO:0022614 membrane to membrane docking GO:0030098 lymphocyte differentiation GO:0030183 B cell differentiation GO:0030198 extracellular matrix organization GO:0031589 cell-substrate adhesion GO:0031667 response to nutrient levels GO:0032496 response to lipopolysaccharide GO:0032943 mononuclear cell proliferation GO:0032944 regulation of mononuclear cell proliferation GO:0032946 positive regulation of mononuclear cell proliferation GO:0034341 response to interferon-gamma GO:0034612 response to tumor necrosis factor GO:0035094 response to nicotine GO:0035584 calcium-mediated signaling using intracellular calcium source GO:0035924 cellular response to vascular endothelial growth factor stimulus GO:0036293 response to decreased oxygen levels GO:0042098 T cell proliferation GO:0042102 positive regulation of T cell proliferation GO:0042110 T cell activation GO:0042113 B cell activation GO:0042129 regulation of T cell proliferation GO:0043062 extracellular structure organization GO:0043279 response to alkaloid GO:0045123 cellular extravasation GO:0045471 response to ethanol GO:0045785 positive regulation of cell adhesion GO:0046651 lymphocyte proliferation GO:0050670 regulation of lymphocyte proliferation GO:0050671 positive regulation of lymphocyte proliferation GO:0050863 regulation of T cell activation GO:0050865 regulation of cell activation GO:0050867 positive regulation of cell activation GO:0050870 positive regulation of T cell activation GO:0050900 leukocyte migration GO:0050901 leukocyte tethering or rolling GO:0051249 regulation of lymphocyte activation GO:0051251 positive regulation of lymphocyte activation GO:0060326 cell chemotaxis GO:0060333 interferon-gamma-mediated signaling pathway GO:0061756 leukocyte adhesion to vascular endothelial cell GO:0070482 response to oxygen levels GO:0070486 leukocyte aggregation GO:0070489 T cell aggregation GO:0070661 leukocyte proliferation GO:0070663 regulation of leukocyte proliferation GO:0070665 positive regulation of leukocyte proliferation GO:0071346 cellular response to interferon-gamma GO:0071356 cellular response to tumor necrosis factor GO:0071593 lymphocyte aggregation GO:0097305 response to alcohol GO:0098742 cell-cell adhesion via plasma-membrane adhesion molecules GO:1903037 regulation of leukocyte cell-cell adhesion GO:1903039 positive regulation of leukocyte cell-cell adhesion GO:1990267 response to transition metal nanoparticle
Molecular Function	GO:0005178 integrin binding GO:0008131 primary amine oxidase activity GO:0016638 oxidoreductase activity, acting on the CH-NH2 group of donors GO:0016641 oxidoreductase activity, acting on the CH-NH2 group of donors, oxygen as acceptor GO:0050839 cell adhesion molecule binding
Cellular Component	GO:0002102 podosome GO:0005769 early endosome GO:0005902 microvillus GO:0009897 external side of plasma membrane GO:0015629 actin cytoskeleton GO:0030175 filopodium GO:0042383 sarcolemma GO:0045177 apical part of cell GO:0071065 alpha9-beta1 integrin-vascular cell adhesion molecule-1 complex GO:0098552 side of membrane GO:0098858 actin-based cell projection

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04064 NF-kappa B signaling pathway hsa04514 Cell adhesion molecules (CAMs) hsa04668 TNF signaling pathway hsa04670 Leukocyte transendothelial migration
Reactome	R-HSA-1280218: Adaptive Immune System R-HSA-1280215: Cytokine Signaling in Immune system R-HSA-1474244: Extracellular matrix organization R-HSA-168256: Immune System R-HSA-198933: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell R-HSA-216083: Integrin cell surface interactions R-HSA-913531: Interferon Signaling R-HSA-877300: Interferon gamma signaling R-HSA-6785807: Interleukin-4 and 13 signaling R-HSA-449147: Signaling by Interleukins

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa04064 NF-kappa B signaling pathway
hsa04514 Cell adhesion molecules (CAMs)
hsa04668 TNF signaling pathway
hsa04670 Leukocyte transendothelial migration

Reactome

R-HSA-1280218: Adaptive Immune System
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-1474244: Extracellular matrix organization
R-HSA-168256: Immune System
R-HSA-198933: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-216083: Integrin cell surface interactions
R-HSA-913531: Interferon Signaling
R-HSA-877300: Interferon gamma signaling
R-HSA-6785807: Interleukin-4 and 13 signaling
R-HSA-449147: Signaling by Interleukins

Summary
Symbol	VCAM1
Name	vascular cell adhesion molecule 1
Aliases	CD106; INCAM-100; CD106 antigen; CD antigen CD106; VCAM-1; V-CAM 1; Vascular cell adhesion protein 1
Chromosomal Location	1p32-p31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between VCAM1 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 VCAM1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
28235946	Clear Cell Renal Cell Carcinoma	Promote immunity	Vascular cell adhesion molecule 1 (VCAM-1) is an adhesion molecule assigned to the activated endothelium mediating immune cells adhesion and extravasation.
21170961	Melanoma	Promote immunity (infiltration)	Enhanced Type-1 T cell infiltration of tumors was associated with treatment-induced expression of vascular cell adhesion molecule-1 (VCAM-1) and CXCR3 ligand chemokines in vascular/peri-vascular cells within the TME, with SUT/VAC therapy benefits conditionally negated upon adminsitration of CXCR3 or VCAM-1 blocking antibodies.
20154208	B16 Malignant Melanoma; Lymphoma	Promote immunity (infiltration)	Small-molecule inhibitors of vascular adhesion protein-1 reduce the accumulation of myeloid cells into tumors and attenuate tumor growth in mice. We found that both anti-VAP-1 Abs and VAP-1 inhibitors reduced the number of leukocytes in the tumors, but they targeted partially different leukocyte subpopulations. Anti-VAP-1 Abs selectively inhibited infiltration of CD8-positive lymphocytes into tumors and had no effect on accumulation of myeloid cells into tumors. In contrast, the VAP-1 inhibitors significantly reduced only the number of proangiogenic Gr-1(+)CD11b(+) myeloid cells in melanomas and lymphomas. Blocking of VAP-1 by either means left tumor homing of regulatory T cells and type 2 immune-suppressing monocytes/macrophages intact. The VAP-1 inhibitors also reduced the binding of Gr-1(+) myeloid cells to the tumor vasculature. We conclude that tumors use the catalytic activity of VAP-1 to recruit myeloid cells into tumors and to support tumor progression.
17616653	Renal Cell Carcinoma	Inhibit immunity	One recent study has shown that tumor cells can escape T-cell immunity by overexpressing the endothelial cell adhesion molecule vascular cell adhesion molecule-1 (VCAM-1), which normally mediates leukocyte extravasion to sites of tissue inflammation. Renal cell carcinoma (RCC) was identified as one tumor type where VCAM-1 is commonly highly overexpressed. Together, our findings suggest that RCCs might exploit VCAM-1 overexpression for immune escape.
21805477	Hepatocellular Carcinoma	Promote immunity (infiltration)	Calreticulin (CRT), a chaperone protein mainly located in the endoplasmic reticulum, has been shown to exert anti-angiogenic activity and inhibit tumor growth. Here, we demonstrate that in addition to inhibiting angiogenesis, CRT also enhances the expression of both ICAM-1 and VCAM-1 on tumor endothelial cells. This expression results in enhanced leukocyte-endothelial cell interactions and increased lymphocyte infiltration into tumors.

Summary
Symbol	VCAM1
Name	vascular cell adhesion molecule 1
Aliases	CD106; INCAM-100; CD106 antigen; CD antigen CD106; VCAM-1; V-CAM 1; Vascular cell adhesion protein 1
Chromosomal Location	1p32-p31
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 VCAM1 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	VCAM1
Name	vascular cell adhesion molecule 1
Aliases	CD106; INCAM-100; CD106 antigen; CD antigen CD106; VCAM-1; V-CAM 1; Vascular cell adhesion protein 1
Chromosomal Location	1p32-p31
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 VCAM1 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	-0.64	0.206
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.797	0.623
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.535	0.698
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.433	0.286
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.09	0.962
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.873	0.736
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.186	0.75
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.131	0.934
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.264	0.879
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.646	0.82
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	-0.121	0.977
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.089	0.652

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of VCAM1 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	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	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	0	2.7	-2.7	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	0	3.4	-3.4	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	14.3	0	14.3	0.238
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	0	12.5	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	15.4	0	15.4	0.482
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	6.2	-6.2	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	14.3	-14.3	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	3.7	-3.7	0.415
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	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	VCAM1
Name	vascular cell adhesion molecule 1
Aliases	CD106; INCAM-100; CD106 antigen; CD antigen CD106; VCAM-1; V-CAM 1; Vascular cell adhesion protein 1
Chromosomal Location	1p32-p31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of VCAM1. 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	VCAM1
Name	vascular cell adhesion molecule 1
Aliases	CD106; INCAM-100; CD106 antigen; CD antigen CD106; VCAM-1; V-CAM 1; Vascular cell adhesion protein 1
Chromosomal Location	1p32-p31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of VCAM1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by VCAM1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	VCAM1
Name	vascular cell adhesion molecule 1
Aliases	CD106; INCAM-100; CD106 antigen; CD antigen CD106; VCAM-1; V-CAM 1; Vascular cell adhesion protein 1
Chromosomal Location	1p32-p31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of VCAM1. 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	VCAM1
Name	vascular cell adhesion molecule 1
Aliases	CD106; INCAM-100; CD106 antigen; CD antigen CD106; VCAM-1; V-CAM 1; Vascular cell adhesion protein 1
Chromosomal Location	1p32-p31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of VCAM1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	VCAM1
Name	vascular cell adhesion molecule 1
Aliases	CD106; INCAM-100; CD106 antigen; CD antigen CD106; VCAM-1; V-CAM 1; Vascular cell adhesion protein 1
Chromosomal Location	1p32-p31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between VCAM1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	VCAM1
Name	vascular cell adhesion molecule 1
Aliases	CD106; INCAM-100; CD106 antigen; CD antigen CD106; VCAM-1; V-CAM 1; Vascular cell adhesion protein 1
Chromosomal Location	1p32-p31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting VCAM1 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting VCAM1.

ID	Name	Drug Type	Targets	#Targets
DB00898	Ethanol	Small Molecule	CACNA1C, CACNA1D, CACNA1S, CACNB1, CACNG1, CACNG2, CHRNA10, CHRNA2 ......	52
DB01136	Carvedilol	Small Molecule	ADRA1A, ADRA1B, ADRA1D, ADRA2A, ADRA2B, ADRA2C, ADRB1, ADRB2, GJA1 ......	17
DB05399	Succinobucol	Small Molecule	VCAM1	1

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