TISIDB

Summary
Symbol	LGALS3
Name	lectin, galactoside-binding, soluble, 3
Aliases	MAC-2; GALIG; galectin 3; CBP35; GAL3; GALBP; MAC2; 35 kDa lectin; IgE-binding protein; MAC-2 antigen; carbo ......
Chromosomal Location	14q22.3
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	Cytoplasm. Nucleus. Secreted. Note=Secreted by a non-classical secretory pathway and associates with the cell surface.
Domain	PF00337 Galactoside-binding lectin
Function	Galactose-specific lectin which binds IgE. May mediate with the alpha-3, beta-1 integrin the stimulation by CSPG4 of endothelial cells migration. Together with DMBT1, required for terminal differentiation of columnar epithelial cells during early embryogenesis (By similarity). In the nucleus: acts as a pre-mRNA splicing factor. Involved in acute inflammatory responses including neutrophil activation and adhesion, chemoattraction of monocytes macrophages, opsonization of apoptotic neutrophils, and activation of mast cells.

> Gene Ontology [ TOP ]
Biological Process	GO:0001771 immunological synapse formation GO:0002263 cell activation involved in immune response GO:0002285 lymphocyte activation involved in immune response GO:0002286 T cell activation involved in immune response GO:0002291 T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell GO:0002366 leukocyte activation involved in immune response GO:0002429 immune response-activating cell surface receptor signaling pathway GO:0002548 monocyte chemotaxis GO:0002683 negative regulation of immune system process GO:0002685 regulation of leukocyte migration GO:0002687 positive regulation of leukocyte migration GO:0002694 regulation of leukocyte activation GO:0002695 negative regulation of leukocyte activation GO:0002697 regulation of immune effector process GO:0002698 negative regulation of immune effector process GO:0002757 immune response-activating signal transduction GO:0002764 immune response-regulating signaling pathway GO:0002768 immune response-regulating cell surface receptor signaling pathway GO:0006397 mRNA processing GO:0006816 calcium ion transport GO:0007159 leukocyte cell-cell adhesion GO:0007162 negative regulation of cell adhesion GO:0008037 cell recognition GO:0008380 RNA splicing GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors GO:0009988 cell-cell recognition GO:0010959 regulation of metal ion transport GO:0022407 regulation of cell-cell adhesion GO:0022408 negative regulation of cell-cell adhesion GO:0030100 regulation of endocytosis GO:0030335 positive regulation of cell migration GO:0030593 neutrophil chemotaxis GO:0030595 leukocyte chemotaxis GO:0032943 mononuclear cell proliferation GO:0032944 regulation of mononuclear cell proliferation GO:0040017 positive regulation of locomotion GO:0042098 T cell proliferation GO:0042110 T cell activation GO:0042129 regulation of T cell proliferation GO:0043270 positive regulation of ion transport GO:0045806 negative regulation of endocytosis GO:0046651 lymphocyte proliferation GO:0048245 eosinophil chemotaxis GO:0048246 macrophage chemotaxis GO:0050670 regulation of lymphocyte proliferation GO:0050777 negative regulation of immune response GO:0050851 antigen receptor-mediated signaling pathway GO:0050852 T cell receptor signaling pathway GO:0050854 regulation of antigen receptor-mediated signaling pathway GO:0050856 regulation of T cell receptor signaling pathway GO:0050858 negative regulation of antigen receptor-mediated signaling pathway GO:0050860 negative regulation of T cell receptor signaling pathway GO:0050863 regulation of T cell activation GO:0050865 regulation of cell activation GO:0050866 negative regulation of cell activation GO:0050868 negative regulation of T cell activation GO:0050900 leukocyte migration GO:0050918 positive chemotaxis GO:0051051 negative regulation of transport GO:0051249 regulation of lymphocyte activation GO:0051250 negative regulation of lymphocyte activation GO:0051272 positive regulation of cellular component movement GO:0051924 regulation of calcium ion transport GO:0051928 positive regulation of calcium ion transport GO:0060326 cell chemotaxis GO:0060627 regulation of vesicle-mediated transport GO:0070227 lymphocyte apoptotic process GO:0070228 regulation of lymphocyte apoptotic process GO:0070231 T cell apoptotic process GO:0070232 regulation of T cell apoptotic process GO:0070486 leukocyte aggregation GO:0070489 T cell aggregation GO:0070509 calcium ion import GO:0070661 leukocyte proliferation GO:0070663 regulation of leukocyte proliferation GO:0070838 divalent metal ion transport GO:0071593 lymphocyte aggregation GO:0071621 granulocyte chemotaxis GO:0071674 mononuclear cell migration GO:0071675 regulation of mononuclear cell migration GO:0071677 positive regulation of mononuclear cell migration GO:0071887 leukocyte apoptotic process GO:0072511 divalent inorganic cation transport GO:0072677 eosinophil migration GO:0090279 regulation of calcium ion import GO:0090280 positive regulation of calcium ion import GO:0097191 extrinsic apoptotic signaling pathway GO:0097529 myeloid leukocyte migration GO:0097530 granulocyte migration GO:1902041 regulation of extrinsic apoptotic signaling pathway via death domain receptors GO:1903037 regulation of leukocyte cell-cell adhesion GO:1903038 negative regulation of leukocyte cell-cell adhesion GO:1990266 neutrophil migration GO:2000106 regulation of leukocyte apoptotic process GO:2000147 positive regulation of cell motility GO:2000520 regulation of immunological synapse formation GO:2000521 negative regulation of immunological synapse formation GO:2001188 regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell GO:2001189 negative regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell GO:2001233 regulation of apoptotic signaling pathway GO:2001234 negative regulation of apoptotic signaling pathway GO:2001236 regulation of extrinsic apoptotic signaling pathway GO:2001237 negative regulation of extrinsic apoptotic signaling pathway
Molecular Function	GO:0019863 IgE binding GO:0019865 immunoglobulin binding GO:0030246 carbohydrate binding GO:0042056 chemoattractant activity GO:0043236 laminin binding GO:0050840 extracellular matrix binding
Cellular Component	GO:0001772 immunological synapse GO:0005681 spliceosomal complex GO:0005743 mitochondrial inner membrane

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-879415: Advanced glycosylation endproduct receptor signaling R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-6798695: Neutrophil degranulation

Summary
Symbol	LGALS3
Name	lectin, galactoside-binding, soluble, 3
Aliases	MAC-2; GALIG; galectin 3; CBP35; GAL3; GALBP; MAC2; 35 kDa lectin; IgE-binding protein; MAC-2 antigen; carbo ......
Chromosomal Location	14q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between LGALS3 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 LGALS3 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
25691328	Malignant Neoplasms of the Mouse Mammary Gland	Inhibit immunity (T cell function)	Galectin-3 Shapes Antitumor Immune Responses by Suppressing CD8+ T Cells via LAG-3 and Inhibiting Expansion of Plasmacytoid Dendritic Cells.
23479624	Prostate Carcinoma	Inhibit immunity	Here, we show that a β-galactoside-binding lectin [galectin-3 (gal3)] that recognizes the Thomsen-Friedenreich disaccharide (TFD, Galβ1,3GalNAc) present on the surface of most cancer cells is involved in promoting angiogenesis, tumor-endothelial cell adhesion, and metastasis of prostate cancer cells, as well as evading immune surveillance through killing of activated T cells.
21712812	Bladder Carcinoma	Inhibit immunity	Engagement of an NK-activating receptor, NKG2D, by its tumour-associated ligand, Major histocompatibility complex class I-related chain A (MICA), is critical to tumour rejection by NK cells. In C2GnT-expressing bladder tumour cells, poly-N-acetyllactosamine was present on core2 O-glycans on MICA, and galectin-3 bound the NKG2D-binding site of MICA through this poly-N-acetyllactosamine. Galectin-3 reduced the affinity of MICA for NKG2D, thereby severely impairing NK cell activation and silencing the NK cells.
18757439	Melanoma; Colon Carcinoma	Inhibit immunity	T-cell activation induced by Gal-3 resulted in T-cell apoptosis. We showed that a high level of expression of Gal-3 promoted tumor growth in vitro and in vivo. Using a mouse tumor model, we showed that delivery of high doses of Gal-3 inhibited tumor-reactive T cells and promoted tumor growth in mice receiving tumor-reactive CD8(+) T cells.

Summary
Symbol	LGALS3
Name	lectin, galactoside-binding, soluble, 3
Aliases	MAC-2; GALIG; galectin 3; CBP35; GAL3; GALBP; MAC2; 35 kDa lectin; IgE-binding protein; MAC-2 antigen; carbo ......
Chromosomal Location	14q22.3
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 LGALS3 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	LGALS3
Name	lectin, galactoside-binding, soluble, 3
Aliases	MAC-2; GALIG; galectin 3; CBP35; GAL3; GALBP; MAC2; 35 kDa lectin; IgE-binding protein; MAC-2 antigen; carbo ......
Chromosomal Location	14q22.3
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 LGALS3 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	0.109	0.821
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.232	0.956
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.033	0.991
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.511	0.263
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.044	0.983
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	1.108	0.686
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.02	0.975
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.227	0.922
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.314	0.904
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.244	0.908
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	0.434	0.901
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.017	0.88

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of LGALS3 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	0	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	0	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	4.5	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	1

Summary
Symbol	LGALS3
Name	lectin, galactoside-binding, soluble, 3
Aliases	MAC-2; GALIG; galectin 3; CBP35; GAL3; GALBP; MAC2; 35 kDa lectin; IgE-binding protein; MAC-2 antigen; carbo ......
Chromosomal Location	14q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of LGALS3. 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	LGALS3
Name	lectin, galactoside-binding, soluble, 3
Aliases	MAC-2; GALIG; galectin 3; CBP35; GAL3; GALBP; MAC2; 35 kDa lectin; IgE-binding protein; MAC-2 antigen; carbo ......
Chromosomal Location	14q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of LGALS3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by LGALS3. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	LGALS3
Name	lectin, galactoside-binding, soluble, 3
Aliases	MAC-2; GALIG; galectin 3; CBP35; GAL3; GALBP; MAC2; 35 kDa lectin; IgE-binding protein; MAC-2 antigen; carbo ......
Chromosomal Location	14q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of LGALS3. 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	LGALS3
Name	lectin, galactoside-binding, soluble, 3
Aliases	MAC-2; GALIG; galectin 3; CBP35; GAL3; GALBP; MAC2; 35 kDa lectin; IgE-binding protein; MAC-2 antigen; carbo ......
Chromosomal Location	14q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of LGALS3 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	LGALS3
Name	lectin, galactoside-binding, soluble, 3
Aliases	MAC-2; GALIG; galectin 3; CBP35; GAL3; GALBP; MAC2; 35 kDa lectin; IgE-binding protein; MAC-2 antigen; carbo ......
Chromosomal Location	14q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between LGALS3 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	LGALS3
Name	lectin, galactoside-binding, soluble, 3
Aliases	MAC-2; GALIG; galectin 3; CBP35; GAL3; GALBP; MAC2; 35 kDa lectin; IgE-binding protein; MAC-2 antigen; carbo ......
Chromosomal Location	14q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting LGALS3 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting LGALS3.

ID	Name	Drug Type	Targets	#Targets
DB01827	2,3,5,6-Tetrafluoro-4-Methoxy-Benzamide	Small Molecule	LGALS3	1
DB04465	Lactose	Small Molecule	GLT6D1, GLTP, LGALS3	3

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