ETS1

Protein ETS1

Identifiers
ETS proto-oncogene 1, transcription factor
HUGO:ETS1 hgnc_id:HGNC:3488 HGNC:3488 ENTREZ:2113 UNIPROT:P14921
v-ets erythroblastosis virus E26 oncogene homolog 1 (avian)
HUGO:ETS1, HGNC:3488, ENTREZ:2113, UNIPROT:P14921, GENECARDS:GC11M128328
HUGO:ETS1

Maps_Modules
HMC:TUMOR_PROMOTING_INFLAMMATION
HMC:ACTIVATING_INVASION_AND_METASTASIS
Cancer Associated Fibroblasts / CORE
Cancer Associated Fibroblasts / FIBROBLAST_ACTIVATION_MARKERS
EMT Senescence / EMT_REGULATORS
HMC:AVOIDING_IMMUNE_DESTRUCTION
Innate Immunity / MIRNA_TF_IMMUNOSTIMULATORY

References
CASCADE:TGFB
PMID:15001984
Tenascin-C upregulation by transforming growth factor-?? in human dermal fibroblasts involves Smad3, Sp1, and Ets1
Smad3 complex interact with SP1 and ETS1 and induces activity of TN-C promoter.
PMID:16391805
Ets-1 is a transcription factor
Ets-1 involves in inducing MMP2 expression by EMT in human squamous carcinoma cells
PMID:9157999
VEGF increased the level of ETS1 mRNA in human umbifical vein endothelial cells and lung microvascular endothelial cells over 5-fold.
Protein levels were shown to increase concordantly.
PMID:15111329
The Ets gene family conserves an 85-amino acid DNA-binding ETS domain that binds the consensus sequence 5'-GGA(A/T)-3' in the promoter region of the target genes.
Ets has various biological functions, including cellular growth, differentiation, and organ development.
Ets-1, first identified among the Ets gene family, has been shown to also be associated with pathological angiogenesis.
A number of angiogenesis-related molecules, including MMP-1, MMP-3, MMP-9, integrin 3, vascular endothelial cadherin (VE-cadherin), and neuropilin-1 (NRP1) are reported to be targets of Ets-1 in endothelial cells
PMID:21081489
Endogenous Ets-1 is a key mediator of cell migration and Matrigel tube formation in HMECs (human microvascular endothelial cells)
PMID:21041997
In cells induced to undergo EMT, TGFB also activates the expresion of ZEB1 and ZEB2 through upregulation of ETS1 expression, which then may cooperate with the bHLH transcription factor E47 (TCF3)
PMID:17615296
TGFB induces ETS1 transcriptional expression.
TGFB represses ID2 and ID3 transcriptional expression (PMID:15121845 and PMID:15181457)
ID2 may regulate the function of Ets1 to modulate the transcription of ZEB1 and ZEB2 without alteration of the transcription of Ets1.
Ets1 may act as an inducer of ZEB1 in collaboration with E47 (TCF3)
NATURAL_KILLER
CASCADE:IL15
CASCADE:IL2
PMID:22608498
ETS1 binds directly to the Tbx21 and IL2RB (CD122) genes and induces its expression in NK cells.
expression of Ncr1 (NKp46), Cd122 (il2RB), Idb2, Ltb, Lair1 and Tbx21 mRNA is reduced in NK cells after knockdown of ETS1.

ETS1@Nucleus

References
em_emtc_emtc_re355( EMT Senescence ):
PMID:21317430
Snail1 induces the nuclear translocation of Ets1, another factor required for Zeb1 expression.
Both Twist and Ets1 bind to the ZEB1 promoter although to different elements: whereas Ets1 interacts with the proximal promoter, Twist does it with a 700-bp sequence upstream of the transcription start site.
Snail1 controls Zeb1 expression at multiple levels and acts cooperatively with Twist in the ZEB1 gene transcription induction.
em_emtc_emtc_re22( EMT Senescence ):
PMID:10048576
The gene expressions of MMP-1, MMP-3, and MMP-9 and gelatinolytic activity of MMP-9 were significantly increased in high ETS-1 expression cells.
Low ETS-1 expression cells could not spread on a vitronectin substratum, and the phosphorylation of focal adhesion kinase was markedly impaired because of the reduced expression of integrin b3
PMID:19208835
TCF8 (ZEB1) regulates cell invasion and migration via MMP1 expression.
TCF8 is likely to be dispensable for endothelial cell motility.
One possible mechanism underlying the increased invasiveness and migration might be the up-regulated digestion of ECMs via TCF8-mediated transcriptional regulation of the gene encoding MMP1.
MMP1 induction during tube formation was significantly enhanced in Matrigel when TCF8 was silenced
PMID:21081489
MiR-200b Regulates Ets-1-associated Genes
Suppression of endogenous miR-200b induced MMP-1 and VEGFR2 expressions
Overexpression of Ets-1 did not completely reverse miR- 200b-associated MMP-1 and VEGFR2 down-regulation.
It indicates that miR-200b, apart from targeting Ets-1, might silence other target proteins involved in transcription of the indicated genes.
PMID:20589835
Our results indicate that MT1-MMP is a direct down-stream target in the Wnt signaling pathway, and that one of the ways accumulated beta-catenin contributes to colorectal carcinogenesis is by transactivating this gene.
MT1-MMP is one target gene of Lef-1/Tcf-4 (Takahashi et al, 2002)
PMID:22439866
c-Myb strongly increased the expression/activity of cathepsin D and matrix metalloproteinase (MMP) 9 and significantly downregulated MMP1.
PMID:9811054
Nuclear factor kappaB/p50 activates an element in the distal matrix metalloproteinase 1 promoter in interleukin-1beta-stimulated synovial fibroblasts.
PMID:16556862
ROS regulate MMP gene expression and activation of proenzymes. MMP-1, MMP-2, MMP-7, and MMP-9 are activated by ROS through interactions with thiol groups
em_emtc_emtc_re63( EMT Senescence ):
PMID:15003528
NF-kappaB binds to a polymorphic repressor element in the MMP-3 promoter.
em_emtc_emtc_re65( EMT Senescence ):
PMID:16079281
MMP-9 transcription is activated in response to Snail expression
Oncogenic H-Ras (RasV12) synergistically co-operates with Snail in the induction of MMP-9 transcription and expression.
Phosphorylated Sp-1 is recruited to the MMP-9 promoter following activation of the Erk1/2 pathway
PMID:19564415
The transcription factor FOXO3, negatively regulated by binding to 14-3-3 protein family, induces MMP9 and MMP13 expression.
This explains the role of FOXO3 in promoting tumor invasion.
PMID:8844971
Molecular mechanism of transcriptional activation of human gelatinase B (=MMP9) by proximal promoter. (NFKB)
em_emtc_emtc_re177( EMT Senescence ):
PMID:7512751
PMID:7528107
Integrin aVb3 plays an important role in angiogenesis. Bblocking of the binding of endothelial integrin aVb3 inhibits angiogenesis and forces neovascular ECs into apoptosis (Brooks et al., 1994a,b).
PMID:24376839
PTP4A3 is implicated in cell adhesion and the regulation of focal adhesion components including integrin beta-1, Src, paxillin and p130Cas
Similarly, PTP4A3 promotes cell invasion by increasing MMP2 activity and decreasing the expression of the MMP inhibitor, TIMP2.
PTP4A3 is also involved in EMT: PTP4A3 overexpression in colorectal carcinoma cells downregulates epithelial markers (E-cadherin, plakoglobin, and integrin beta-3) and upregulates expression of mesenchymal markers (fibronectin and snail1).
PMID:23691193
Src-mediated phosphorylation of PTP4A3 Is required for Rho activation, motility and invasion promoted by PTP4A3.
em_emtc_emtc_re369( EMT Senescence ):
Ets-1 is a key transcription factor that is known to support angiogenesis.
Certain pro-angiogenic stimulus induce Ets-1 expression, such as:
PMID:9157999
VEGF increased the level of ETS1 mRNA in human umbifical vein endothelial cells and lung microvascular endothelial cells over 5-fold.
Protein levels were shown to increase concordantly.
PMID:15111329
VEGF is a predominant angiogenic factor that mediates ocular neovascularization.
VEGF is increased by hypoxia, which is one of the primary stimuli for ocular neovascularization.
VEGF induces Ets-1 expression in bovine retinal endothelial cells and its expression is PKC/ERK pathway-dependent.
Ets-1 up-regulation is involved in the development of retinal neovascularization, and inhibition of Ets-1 may be beneficial in the treatment of ischemic ocular diseases
PMID:17872466
Angiotensin II is a potent mediator of vascular inflammation through the generation of reactive oxygen species (ROS).
Ang II???induced ROS production and medial hypertrophy in the thoracic aorta were markedly diminished as a result of blocking Ets-1.
Ets-1 functions as a critical downstream transcriptional mediator of Ang II ROS generation by regulating the expression of NAD(P)H oxidase subunits such as p47phox
PMID:18337545
Angiotensin II increases the expression of the transcription factor ETS-1 in mesangial cells
Mesangial cells are specialized cells around blood vessels in the kidneys, at the mesangium
PMID:16682805
Fibroblast growth factor FGF1, a prototypic member of the FGF family, has the ability to stimulate angiogenesis in an in vivo model of angiogenesis.
This FGF1-mediated angiogenesis involves in the PI3K/AKT pathway.
Both activity and mRNA expression levels of the Ets1 molecule were increased in response to FGF1 overexpression
Ets-1 activation is a requisite for FGF1-mediated angiogenesis in vivo.

Modifications:
In compartment: Cytosol

ETS1@Cytosol

In compartment: INNATE_IMMUNE_CELL_Cytosol

ETS1@INNATE_IMMUNE_CELL_Cytosol

In compartment: Nucleus

ETS1@Nucleus

Participates in complexes:

Participates in reactions:
As Reactant or Product:

As Catalyser: