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EPAS1 — VEGFA
Pathways - manually collected, often from reviews:
-
KEGG Pathways in cancer:
EPAS1/HIF1A
→
FIGF/PGF/VEGFA/VEGFB/VEGFC
(gene expression, expression)
-
KEGG Renal cell carcinoma:
EPAS1/HIF1A
→
FIGF/PGF/VEGFA/VEGFB/VEGFC
(gene expression, expression)
-
KEGG Renal cell carcinoma:
EPAS1/HIF1A
→
FIGF/PGF/VEGFA/VEGFB/VEGFC
(gene expression, expression)
Text-mined interactions from Literome
Elvert et al., Mech Dev 1999
:
Unlike HIF-1alpha - the founding member of the HIF family - which is expressed more or less ubiquitously,
HIF-2alpha ( also called HRF, HLF and EPAS1 ) is highly expressed by vascular endothelial cells and was shown to
activate the transcription of endothelial cell-specific receptor tyrosine kinases ( tie-2 and flk-1/VEGF receptor 2 ) and of
vascular endothelial growth factor ( VEGF )
Maemura et al., J Biol Chem 1999
:
In this report, we show that
EPAS1 increased
VEGF gene expression through the HIF-1 binding site ... Because a truncated EPAS1 protein lacking the transactivation domain at amino acids 486-639 eliminated
induction of the
VEGF promoter by wild-type
EPAS1 , the truncated protein functions as a dominant negative mutant ... Since VEGF plays a crucial role in angiogenesis, the ability of dominant negative
EPAS1 to
inhibit VEGF promoter activity raises the possibility of a novel approach to inhibiting pathological angiogenesis
Akeno et al., Endocrinology 2001
(Anoxia) :
Hypoxia
induces vascular endothelial growth factor gene transcription in human osteoblast-like cells through the
hypoxia-inducible factor-2alpha ... Hypoxia
induced VEGF promoter activity five-fold by 24 h. Forced expression of
Hif-2alpha , but not Hif-1alpha, increased both basal and hypoxia induced VEGF promoter activity ... In summary, exposure of osteoblast-like cells to hypoxia induces VEGF expression via induction of
Hif-2alpha and transcriptional
activation of the
VEGF promoter
Xia et al., Cancer 2001
(Carcinoma, Renal Cell...) :
Regulation of
vascular endothelial growth factor transcription by
endothelial PAS domain protein 1 (EPAS1) and possible involvement of EPAS1 in the angiogenesis of renal cell carcinoma ... These results suggest that endogenous
VEGF can be
up-regulated transcriptionally by
EPAS1 , and EPAS1 may be involved in the angiogenesis of RCC
Blancher et al., Cancer Res 2001
(Breast Neoplasms...) :
Because hypoxia is a major stimulus for VEGF production, we examined the effects of LY294002, a selective PI3K inhibitor, on hypoxia-inducible factor (HIF)-1alpha and
HIF-2alpha expression and on endogenous
VEGF responses to hypoxia
Liang et al., J Biol Chem 2002
(Neuroblastoma) :
A dominant negative
EPAS1 significantly
reduces HS-1100 enhancer activity and
VEGF-A levels in U87MG cells
Hosford et al., Am J Physiol Lung Cell Mol Physiol 2003
(Hyperoxia) :
Levels of HIF-2alpha and VEGF mRNA were correlated in the air but not the O2-treated group, suggesting that the low levels of
HIF-2alpha observed at high O2 concentrations are not
stimulating VEGF expression
Takeda et al., Circ Res 2004
:
In conclusion,
EPAS1 promotes Flt-1 gene expression and
induces mRNA expression of
VEGF , Flk-1, and Tie2, leading to enhancement of mature angiogenesis in vivo
Norrby et al., J Vasc Res 2004
(Body Weight) :
Using the same experimental system, we have now studied the effect of ( i ) ingested human apo-LF, apo-hLF, on angiogenesis mediated by VEGF-A and bFGF, ( ii ) ingested human iron saturated LF, holo-hLF, on
VEGF-A mediated angiogenesis and ( iii ) subcutaneous continuously infused
apo-hLF on VEGF-A mediated angiogenesis
Carroll et al., Cancer Res 2006
(Breast Neoplasms...) :
In contrast, in renal carcinoma cells that constitutively express HIF-1alpha and HIF-2alpha due to loss of VHL function, we found that high basal
VEGF , glucose transporter-1, urokinase-type plasminogen activator receptor, and plasminogen activator inhibitor-1 expression was predominantly
dependent on
HIF-2alpha ... Finally, we showed that a newly identified small-molecule inhibitor of HIF-1, NSC-134754, is also able to significantly decrease HIF-2alpha protein expression and
HIF-2alpha regulated
VEGF levels in renal carcinoma cells
Chavez et al., J Neurosci 2006
(Hypoxia-Ischemia, Brain) :
In contrast, reduction of
HIF-2alpha expression by siHIF-2alpha led to a drastic decrease of EPO hypoxic expression, but it did not
affect LDH or
VEGF upregulation
Koizume et al., Biochem Biophys Res Commun 2008
:
We found by RNA interference experiments that
HIF-2alpha plays a minor role in
VEGF gene upregulation under hypoxia or CoCl ( 2 ) treatment, even when both HIFs are similarly bound to the promoter region
Artman et al., Int J Radiat Oncol Biol Phys 2010
(Carcinoma, Squamous Cell...) :
Downregulation of TGF-beta1 significantly decreased VEGF secretion in radiation-sensitive XF354 cells, and downregulation of HIF-1alpha and
HIF-2alpha reduced PAI-1 and
VEGF secretion in radiation-resistant SAS cells
Saito et al., Nat Med 2010
(Osteoarthritis...) :
HIF-2alpha enhanced promoter activities of COL10A1, MMP13 and
VEGFA through specific binding to the respective hypoxia-responsive elements
Ema et al., Proc Natl Acad Sci U S A 1997
:
The high expression level of HLF mRNA in the O2 delivery system of developing embryos and adult organs suggests that in a normoxic state,
HLF regulates gene expression of
VEGF , various glycolytic enzymes, and others driven by the HRE sequence, and may be involved in development of blood vessels and the tubular system of lung
Wiesener et al., Blood 1998
:
Functional studies in a mutant cell line ( Ka13 ) expressing neither HIF-1alpha nor EPAS-1 confirmed that both proteins interact with hypoxically responsive targets, but suggest target specificity with greater
EPAS-1 transactivation ( relative to HIF-1alpha transactivation ) of the
VEGF promoter than the LDH-A promoter