Gene interactions and pathways from curated databases and text-mining

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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