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MTOR — VEGFA
Text-mined interactions from Literome
Prager et al., Mol Oncol 2010 (Neoplasms) :
VEGF ( 165 ) was constantly secreted by all cultured tumor cells in an
mTOR dependent manner, as it was inhibited by the mTOR inhibitor rapamycin
Jham et al., PloS one 2011 (Inflammation...) :
Conditioned media from vGPCR expressing cells lead to an
mTOR dependent increase in HIF-1a and HIF-2a protein levels and
VEGF upregulation
Calabrò et al., Expert Rev Anticancer Ther 2010 (Carcinoma, Renal Cell...) :
The recent emergence of effective molecular targeted therapies, such as antibodies neutralizing
VEGF ,
inhibitors of tyrosine kinase and
mTOR inhibitors, has sparked an interest in their use prior to surgical resection of renal cell carcinoma (RCC), a practice commonly used in the treatment of many other advanced solid tumors
Kobayashi et al., Cancer Sci 2007 (Lymphatic Metastasis...) :
We investigated the
role of
mTOR , which is a downstream kinase of the phosphatidylinositol 3-kinase/Akt pathway, and the MAPK family ( MEK1/2, p38, and JNK ) in the regulation of VEGF-C and
VEGF-A expression in B13LM cells, a lymphatic metastasis-prone pancreatic tumor cell line
Kurmasheva et al., Mol Cancer Ther 2007 (Anoxia) :
Differential
regulation of
vascular endothelial growth factor by Akt and
mammalian target of rapamycin inhibitors in cell lines derived from childhood solid tumors ... Rapamycin, a selective inhibitor of
mTOR , reduced VEGF production in rhabdomyosarcoma cells under normoxic conditions and partially
suppressed hypoxia-driven increases in
VEGF
Yan et al., J Cell Biochem 2010 :
VEGF stimulation
results in
mTOR signaling activation which changes the phosphorylation status of 4E-BP1, the downstream of mTOR signaling, and ultimately contributes to the translation initiation of Livin protein
Falcon et al., Cancer Res 2011 (Neoplasms, Experimental...) :
In this study, we examined the
effects of
mTORC1/2 dual inhibition on
VEGF production, tumor angiogenesis, vascular regression, and vascular regrowth, and we compared the effects of dual inhibition to mTORC1 inhibition alone
Lee et al., Clin Cancer Res 2006 (Neoplasm Invasiveness...) :
In OVCAR-3 and PC-3 cells, the phosphoinositide
3-kinase/Akt/mammalian target of rapamycin/p70S6K and p42/p44 mitogen activated protein kinase pathways were
required for LPA induced HIF-1alpha and
VEGF expressions, whereas only the phosphoinositide 3-kinase/mammalian target of rapamycin/p70S6K pathway was important in SK-Hep1 cells
Edelstein et al., Cell Signal 2011 (Neuroblastoma) :
The RTK for the
vascular endothelial growth factor ( VEGF ), VEGFR2, can signal protein synthesis but whether it cooperates with mAchRs to
mediate mTOR activation has not been demonstrated
Shiojima et al., J Clin Invest 2005 (Cardiomyopathy, Dilated...) :
Enhanced angiogenesis in the acute phase was associated with
mammalian target of rapamycin dependent induction of myocardial
VEGF and angiopoietin-2 expression
Lee et al., Neuro Oncol 2012 (Brain Neoplasms...) :
The North American Brain Tumor Consortium examined the safety, pharmacokinetics, and efficacy of combination therapy with sorafenib, a small molecule inhibitor of Raf,
vascular endothelial growth factor receptor 2, and platelet derived growth factor receptor-ß, and temsirolimus ( CCI-779 ), an
inhibitor of
mammalian target of rapamycin
Hasaneen et al., Am J Physiol Lung Cell Mol Physiol 2007 :
Our results show : 1 ) a significant increase in human lung microvascular endothelial cell ( HMVEC-L ) proliferation, migration, and tube formation following incubation in conditioned media ( CM ) from HASM cells exposed to mechanical strain ; 2 ) mechanical strain of HASM cells induced VEGF expression and release ; 3 ) VEGF neutralizing antibodies inhibited the proliferation, migration, and tube formations of HMVEC-L induced by the strained airway smooth muscle CM ; 4 ) mechanical strain of HASM induced a significant increase in hypoxia-inducible factor-1alpha ( HIF-1alpha ) mRNA and protein, a transcription factor required for VEGF gene transcription ; and 5 ) mechanical strain of HASM
induced HIF-1alpha/VEGF through dual phosphatidylinositol 3-kinase
(PI3K)/Akt/mammalian target of rapamycin (mTOR) and ERK pathways
Basu et al., PloS one 2011 (Kidney Neoplasms) :
We found that the knockdown of raptor ( using siRNA ) significantly decreased CNI induced VEGF promoter activity as observed by promoter-luciferase assay, suggesting the
role of
mTOR complex1 (mTORC1) in CNI induced
VEGF transcription
Land et al., J Biol Chem 2007 (Neoplasms...) :
Our work shows that activation of
mTOR by Ras homologue enriched in brain (Rheb) overexpression potently
enhances the activity of HIF1alpha and
vascular endothelial growth factor ( VEGF ) -A secretion during hypoxia, which is reversed with rapamycin
Brugarolas et al., Cancer Cell 2004 (Hamartoma...) :
However, hypoxia-inducible factor ( HIF ) and
VEGF are
regulated by
mTOR and are likely to play a contributory role
Yang et al., Hepatology 2009 (Liver Neoplasms) :
Consistent with this notion, enhanced expression of
VEGF-A and
activation of
Akt/mTOR signaling , comparable to the levels of paired HCC tissues, were also detected in HBV related nontumorous livers
Pratheeshkumar et al., PloS one 2012 (Neoplasm Invasiveness...) :
Western blot analysis showed that luteolin suppressed
VEGF induced phosphorylation of VEGF receptor 2 and their downstream protein kinases AKT, ERK,
mTOR , P70S6K, MMP-2, and MMP-9 in HUVECs
Slomiany et al., J Pharmacol Exp Ther 2006 (Anoxia) :
IGF-1 stimulated VEGF promoter activity was phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR ( mammalian target of rapamycin ) -dependent, whereas
VEGF secretion was only partially
reduced by inhibition of
PI3K/Akt/mTOR and HIF-1 activities
Aleffi et al., Am J Physiol Gastrointest Liver Physiol 2011 (Neovascularization, Pathologic) :
In conclusion, in HSC exposed to leptin or PDGF, increased expression of
VEGF requires both activation of
mTOR and generation of reactive oxygen species via NADPH-oxidase
Nakamura et al., Mol Cell Neurosci 2011 :
Pharmacologic inhibitors of the Trk tyrosine kinase, PI-3 kinase and
mTOR paths
prevent NGF stimulated increases in HIF-1a and
VEGF
Zheng et al., Cell Biol Int 2009 (Polycystic Kidney, Autosomal Recessive) :
Therefore, we investigated the relationship between the decreased FPC and the protein levels of
mTOR and the inhibitory
effects of rapamycin on the expression of mTOR, Hypoxia-inducible factor-1 alpha ( HIF-1alpha ) and
vascular endothelial growth factor ( VEGF ) in the human 293T cell line
Sun et al., J Pharmacol Exp Ther 2010 (Carcinoma, Adenoid Cystic...) :
The data also showed that the specific suppression of tumor angiogenesis by ISL was caused by down-regulation of
mammalian target of rapamycin (mTOR) pathway
dependent VEGF production by ACC cells, correlating with concurrent activation of c-Jun NH ( 2 ) -terminal kinase ( JNK ) and inhibition of extracellular signal regulated kinase ( ERK )
Yang et al., J Biol Chem 2013 (Neoplasms...) :
The interaction of Gadd45a with
mTOR suppresses STAT3 phosphorylation at Ser-727 and
leads to down-regulated expression of
VEGFa
Pang et al., Cancer Res 2010 (Neovascularization, Pathologic...) :
Celastrol suppressed the
VEGF induced
activation of AKT,
mammalian target of rapamycin (mTOR), and ribosomal protein S6 kinase ( P70S6K )
Joly , Bull Cancer 2011 (Carcinoma, Renal Cell...) :
The perspectives of renal cell carcinoma (RCC) treatment have improved with the development of targeted molecular therapies against
VEGFR/VEGF mediated angiogenesis and
mTOR
Gao et al., Toxicol Appl Pharmacol 2004 (Ovarian Neoplasms) :
Our results also indicated that the
mTOR/FRAP inhibitor, rapamycin,
inhibited 4-OHE2 induced HIF-1alpha and
VEGF-A expression
Pratheeshkumar et al., PloS one 2012 (Neovascularization, Pathologic...) :
Western blot analysis showed that quercetin suppressed
VEGF induced phosphorylation of VEGF receptor 2 and their downstream protein kinases AKT,
mTOR , and ribosomal protein S6 kinase in HUVECs
Del Bufalo et al., Cancer Res 2006 (Breast Neoplasms...) :
A central
role for
mTOR ( and the critical regulator of cap dependent protein translation, eIF4E ) in the regulation of
VEGF production by BT474 cells was further confirmed using a small interfering RNA approach to silence mTOR and eIF4E protein expression
Ikeda et al., Mol Cell Biol 2011 (Disease Models, Animal...) :
In cultured lung epithelial cells, insulin reduced
VEGF expression and transcriptional activity of HIF-2 on VEGF promoter in an
mTOR dependent manner
Roy et al., Cancer Res 2013 (Disease Models, Animal...) :
mTOR blockade
reduced VEGF secretion and formation of tumor vasculature
Ko et al., Nephrol Dial Transplant 2013 (Disease Models, Animal...) :
Experimental deficiency of vascular endothelial growth factor ( VEGF ) induces proteinuria and
mTOR is
required for
VEGF production and signalling