TISIDB

Summary
Symbol	FLT1
Name	fms-related tyrosine kinase 1
Aliases	VEGFR1; vascular endothelial growth factor receptor 1; vascular permeability factor receptor; FLT; fms-relat ......
Chromosomal Location	13q12
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	Isoform 1: Cell membrane; Single-pass type I membrane protein. Endosome. Note=Autophosphorylation promotes ubiquitination and endocytosis.; SUBCELLULAR LOCATION: Isoform 2: Secreted ; SUBCELLULAR LOCATION: Isoform 3: Secreted.; SUBCELLULAR LOCATION: Isoform 4: Secreted.; SUBCELLULAR LOCATION: Isoform 5: Cytoplasm ; SUBCELLULAR LOCATION: Isoform 6: Cytoplasm ; SUBCELLULAR LOCATION: Isoform 7: Cytoplasm
Domain	PF07679 Immunoglobulin I-set domain PF00047 Immunoglobulin domain PF07714 Protein tyrosine kinase
Function	Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell survival, cell migration, macrophage function, chemotaxis, and cancer cell invasion. May play an essential role as a negative regulator of embryonic angiogenesis by inhibiting excessive proliferation of endothelial cells. Can promote endothelial cell proliferation, survival and angiogenesis in adulthood. Its function in promoting cell proliferation seems to be cell-type specific. Promotes PGF-mediated proliferation of endothelial cells, proliferation of some types of cancer cells, but does not promote proliferation of normal fibroblasts (in vitro). Has very high affinity for VEGFA and relatively low protein kinase activity; may function as a negative regulator of VEGFA signaling by limiting the amount of free VEGFA and preventing its binding to KDR. Likewise, isoforms lacking a transmembrane domain, such as isoform 2, isoform 3 and isoform 4, may function as decoy receptors for VEGFA. Modulates KDR signaling by forming heterodimers with KDR. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leading to activation of phosphatidylinositol kinase and the downstream signaling pathway. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Phosphorylates SRC and YES1, and may also phosphorylate CBL. Isoform 1 phosphorylates PLCG. Promotes phosphorylation of AKT1 at 'Ser-473'. Promotes phosphorylation of PTK2/FAK1. Isoform 7 has a truncated kinase domain; it increases phosphorylation of SRC at 'Tyr-418' by unknown means and promotes tumor cell invasion.

> Gene Ontology [ TOP ]
Biological Process	GO:0001525 angiogenesis GO:0002548 monocyte chemotaxis GO:0006644 phospholipid metabolic process GO:0010517 regulation of phospholipase activity GO:0010518 positive regulation of phospholipase activity GO:0010863 positive regulation of phospholipase C activity GO:0014065 phosphatidylinositol 3-kinase signaling GO:0014066 regulation of phosphatidylinositol 3-kinase signaling GO:0014068 positive regulation of phosphatidylinositol 3-kinase signaling GO:0018108 peptidyl-tyrosine phosphorylation GO:0018212 peptidyl-tyrosine modification GO:0019216 regulation of lipid metabolic process GO:0030335 positive regulation of cell migration GO:0030595 leukocyte chemotaxis GO:0030947 regulation of vascular endothelial growth factor receptor signaling pathway GO:0030949 positive regulation of vascular endothelial growth factor receptor signaling pathway GO:0033674 positive regulation of kinase activity GO:0035924 cellular response to vascular endothelial growth factor stimulus GO:0036323 vascular endothelial growth factor receptor-1 signaling pathway GO:0038084 vascular endothelial growth factor signaling pathway GO:0040017 positive regulation of locomotion GO:0043405 regulation of MAP kinase activity GO:0043406 positive regulation of MAP kinase activity GO:0043410 positive regulation of MAPK cascade GO:0043550 regulation of lipid kinase activity GO:0043551 regulation of phosphatidylinositol 3-kinase activity GO:0043552 positive regulation of phosphatidylinositol 3-kinase activity GO:0045765 regulation of angiogenesis GO:0045766 positive regulation of angiogenesis GO:0045834 positive regulation of lipid metabolic process GO:0045860 positive regulation of protein kinase activity GO:0046777 protein autophosphorylation GO:0048010 vascular endothelial growth factor receptor signaling pathway GO:0048015 phosphatidylinositol-mediated signaling GO:0048017 inositol lipid-mediated signaling GO:0048514 blood vessel morphogenesis GO:0050900 leukocyte migration GO:0051272 positive regulation of cellular component movement GO:0060191 regulation of lipase activity GO:0060193 positive regulation of lipase activity GO:0060326 cell chemotaxis GO:0071674 mononuclear cell migration GO:0071900 regulation of protein serine/threonine kinase activity GO:0071902 positive regulation of protein serine/threonine kinase activity GO:0090218 positive regulation of lipid kinase activity GO:0090287 regulation of cellular response to growth factor stimulus GO:0097529 myeloid leukocyte migration GO:1900274 regulation of phospholipase C activity GO:1901342 regulation of vasculature development GO:1903725 regulation of phospholipid metabolic process GO:1903727 positive regulation of phospholipid metabolic process GO:1904018 positive regulation of vasculature development GO:2000147 positive regulation of cell motility
Molecular Function	GO:0004713 protein tyrosine kinase activity GO:0004714 transmembrane receptor protein tyrosine kinase activity GO:0005021 vascular endothelial growth factor-activated receptor activity GO:0019199 transmembrane receptor protein kinase activity GO:0019838 growth factor binding GO:0036326 VEGF-A-activated receptor activity GO:0036327 VEGF-B-activated receptor activity GO:0036332 placental growth factor-activated receptor activity
Cellular Component	GO:0005924 cell-substrate adherens junction GO:0005925 focal adhesion GO:0030055 cell-substrate junction GO:0043235 receptor complex

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04014 Ras signaling pathway hsa04015 Rap1 signaling pathway hsa04060 Cytokine-cytokine receptor interaction hsa04066 HIF-1 signaling pathway hsa04144 Endocytosis hsa04151 PI3K-Akt signaling pathway hsa04510 Focal adhesion
Reactome	R-HSA-194306: Neurophilin interactions with VEGF and VEGFR R-HSA-162582: Signal Transduction R-HSA-194138: Signaling by VEGF R-HSA-195399: VEGF binds to VEGFR leading to receptor dimerization R-HSA-194313: VEGF ligand-receptor interactions

Summary
Symbol	FLT1
Name	fms-related tyrosine kinase 1
Aliases	VEGFR1; vascular endothelial growth factor receptor 1; vascular permeability factor receptor; FLT; fms-relat ......
Chromosomal Location	13q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between FLT1 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

[ TOP ]

Literatures describing the relation between FLT1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
18337760	Kidney Carcinoma	Promote immunity	Sorafenib, a novel drug for metastatic renal cancer, has broad-spectrum activity against multiple tyrosine kinases, including Raf-1, vascular endothelial growth factor receptor and platelet-derived growth factor receptor. These findings suggest that sorafenib may cause the loss of T-cell immune response by inducing apoptosis and targeting LCK. This could potentially lead to immunosuppression in patients with cancer.
23447383	Chronic Lymphocytic Leukemia	Inhibit immunity (T cell function)	In our study, we characterized mRNA levels of VEGF receptors including NRP1 in a large cohort of CLL patients (n = 114), additionally we performed a detailed characterization of NRP1 expression on B cells, plasmacytoid dendritic cells (PDCs) and regulatory T cells (Tregs). The expression of NRP1 was significantly higher on leukemic lymphocytes compared to control B lymphocytes on mRNA and protein levels (22.72% vs. 0.2%, p = 0.0003, respectively), Tregs (42.6% vs. 16.05%, p = 0.0003) and PDCs (100% vs. 98% p < 0.0001). In functional studies, we found higher NRP1 expression on CLL cells after stimulation with VEGF. The correlation between expression of VEGF receptors: FLT1, NRP1 and FOXP3 expression (r(2) = 0.53, p < 0.0001 and r(2) = 0.49, p < 0.0001, respectively) was observed.
21209070	Colon Carcinoma	Promote immunity (T cell function)	Antagonism of VEGF by genetically engineered dendritic cells is essential to induce antitumor immunity against malignant ascites. Using a murine model of MA with CT26 colon cancer cells, we here determined that the imbalance between the VEGF-A/vascular permeability factor and its decoy receptor, soluble fms-like tryrosine kinase receptor-1 (sFLT-1), was a major cause of MA resistance to dendritic cell (DC)-based immunotherapy. These findings were not seen in immunodeficient mice, indicating that a VEGF-A/sFLT-1 imbalance is critical for determining the antitumor immune response by DC-vaccination therapy against MA.
18566400	Renal Cell Carcinoma	Inhibit immunity	Oxidative stress regulates expression of VEGFR1 in myeloid cells: link to tumor-induced immune suppression in renal cell carcinoma. Data suggest that tumor-induced oxidative stress may promote both VEGFR1 up-regulation and immunosuppressive function in bone marrow-derived myeloid cells.

Summary
Symbol	FLT1
Name	fms-related tyrosine kinase 1
Aliases	VEGFR1; vascular endothelial growth factor receptor 1; vascular permeability factor receptor; FLT; fms-relat ......
Chromosomal Location	13q12
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

[ TOP ]

Statistical results of FLT1 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	FLT1
Name	fms-related tyrosine kinase 1
Aliases	VEGFR1; vascular endothelial growth factor receptor 1; vascular permeability factor receptor; FLT; fms-relat ......
Chromosomal Location	13q12
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

[ TOP ]

Points in the above scatter plot represent the expression difference of FLT1 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	-0.811	0.0275
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.951	0.439
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.71	0.452
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.172	0.527
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.275	0.896
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.047	0.985
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.199	0.67
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.436	0.78
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.02	0.99
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.849	0.557
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	2.387	0.21
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.15	0.154

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of FLT1 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	7.4	5.5	1.9	0.66
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	7.1	-7.1	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	7.4	5.1	2.3	0.647
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	14.3	29.4	-15.1	0.426
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	16.7	-4.2	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	15.4	36.4	-21	0.357
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	22.2	0	22.2	0.12
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	20	0	20	0.357
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	25	0	25	0.364
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	15.8	3.7	12.1	0.224
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	9.1	7.7	1.4	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	25	0	25	0.103
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	FLT1
Name	fms-related tyrosine kinase 1
Aliases	VEGFR1; vascular endothelial growth factor receptor 1; vascular permeability factor receptor; FLT; fms-relat ......
Chromosomal Location	13q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of FLT1. 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	FLT1
Name	fms-related tyrosine kinase 1
Aliases	VEGFR1; vascular endothelial growth factor receptor 1; vascular permeability factor receptor; FLT; fms-relat ......
Chromosomal Location	13q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of FLT1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by FLT1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	FLT1
Name	fms-related tyrosine kinase 1
Aliases	VEGFR1; vascular endothelial growth factor receptor 1; vascular permeability factor receptor; FLT; fms-relat ......
Chromosomal Location	13q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of FLT1. 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	FLT1
Name	fms-related tyrosine kinase 1
Aliases	VEGFR1; vascular endothelial growth factor receptor 1; vascular permeability factor receptor; FLT; fms-relat ......
Chromosomal Location	13q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of FLT1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	FLT1
Name	fms-related tyrosine kinase 1
Aliases	VEGFR1; vascular endothelial growth factor receptor 1; vascular permeability factor receptor; FLT; fms-relat ......
Chromosomal Location	13q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between FLT1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	FLT1
Name	fms-related tyrosine kinase 1
Aliases	VEGFR1; vascular endothelial growth factor receptor 1; vascular permeability factor receptor; FLT; fms-relat ......
Chromosomal Location	13q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting FLT1 collected from DrugBank database.

> Drugs from DrugBank database

[ TOP ]

Details on drugs targeting FLT1.

ID	Name	Drug Type	Targets	#Targets
DB00398	Sorafenib	Small Molecule	BRAF, FGFR1, FLT1, FLT3, FLT4, KDR, KIT, PDGFRB, RAF1, RET	10
DB01268	Sunitinib	Small Molecule	CSF1R, FLT1, FLT3, FLT4, KDR, KIT, PDGFRA, PDGFRB	8
DB04879	Vatalanib	Small Molecule	FLT1, FLT4, KDR	3
DB05075	TG-100801	Small Molecule	CSK, FLT1, FLT4, KDR	4
DB05913	OSI-930	Small Molecule	FLT1, KIT	2
DB05932	Denibulin	Small Molecule	FLT1, FLT4, VEGFA	3
DB06080	ABT-869	Small Molecule	CSF1R, FLT1, FLT3, FLT4, KDR, KIT	6
DB06101	IMC-1C11	Biotech	FLT1, FLT4, KDR	3
DB06589	Pazopanib	Small Molecule	FGF1, FGFR3, FLT1, FLT4, ITK, KDR, KIT, PDGFRA, PDGFRB, SH2B3	10
DB06626	Axitinib	Small Molecule	FLT1, FLT4, KDR	3
DB07288	N-(4-chlorophenyl)-2-[(pyridin-4-ylmethyl)amino]benzamide	Small Molecule	FLT1	1
DB08896	Regorafenib	Small Molecule	ABL1, BRAF, DDR2, EPHA2, FGFR1, FGFR2, FLT1, FLT4, FRK, KDR, KIT, ......	18
DB09078	Lenvatinib	Small Molecule	FGFR1, FGFR2, FGFR3, FGFR4, FLT1, FLT4, KDR, KIT	8
DB09079	Nintedanib	Small Molecule	FGFR1, FGFR2, FGFR3, FLT1, FLT3, FLT4, KDR, LCK, LYN, SRC	10
DB09221	Polaprezinc	Small Molecule	FLT1, HSP90AA1, HSP90AB1, IL3, IL6, NGF, PDGFRB, TNF	8

Browse FLT1