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PIK3CA — VEGFA
Pathways - manually collected, often from reviews:
Text-mined interactions from Literome
Banerjee et al., Biochemistry 2008 (Breast Neoplasms) :
Neutralization of VEGF action by its antibody or inhibition of
VEGF induced
PI3K/Akt kinase
activation by wortmannin, a PI3K/Akt specific inhibitor, results in inhibition of VEGF induced hAOSMC migration
Huang et al., J Biol Chem 2002 :
Phosphatidylinositol 3-kinase is
activated by
vascular endothelial growth factor ( VEGF ), and many of the angiogenic cellular responses of VEGF are regulated by the lipid products of phosphatidylinositol 3-kinase
Jang et al., Br J Pharmacol 2013 (Wounds, Penetrating) :
Both an AMPK inhibitor ( compound C ) anda HO-1 activity inhibitor ( SnPPIX ) but not inhibitors of MAPKs,
PI3K and PKC
reduced the production of
VEGF by CKD712
Luangdilok et al., Eur J Cancer 2011 (Carcinoma, Squamous Cell...) :
In both cell lines stimulated with endogenous or exogenous ligand, inhibition of MEK1/2 ( with U0126 or PD98059 ) or
PI3K ( with PI-103 or LY294002 )
resulted in a marked reduction of EGFR induced
VEGF-A expression, whereas exogenous EGF induced VEGF-C upregulation was blocked by inhibitors of MEK but not PI3K
Lu et al., Microvasc Res 2009 (Lung Neoplasms...) :
Furthermore, lenalidomide inhibited
VEGF induced
PI3K-Akt pathway signaling, which is known to regulate adherens junction formation
Li et al., Brain Res Mol Brain Res 2003 (Amyotrophic Lateral Sclerosis...) :
VEGF activated both
PI3-K and MAPK activities in mouse NSC34 motor neuron-like cells
Dong et al., Cancer Res 2001 (Carcinoma, Squamous Cell...) :
Hepatocyte growth factor/scatter factor induced activation of MEK and
PI3K signal pathways
contributes to expression of proangiogenic cytokines interleukin-8 and
vascular endothelial growth factor in head and neck squamous cell carcinoma ... Inhibitors of MEK ( U0126 ) and
PI3K ( LY294002 ) blocked p42/p44 ( erk ) and Akt, respectively, and partially
blocked HGF induced production of IL-8 and
VEGF , whereas the combination of U0126 and LY294002 completely inhibited expression of IL-8 and VEGF by UMSCC-11A
Lo et al., International journal of molecular sciences 2013 :
In parallel,
VEGF induced JNK,
PI3K and Akt activation
Westra et al., BMC musculoskeletal disorders 2010 (Arthritis...) :
THP-1 and SF macrophages produced high levels of VEGF, IL-8, and MMP-9, and
VEGF protein production was significantly
inhibited by
PI3K-inhibitor , and by both CaMKII inhibitors
Sun et al., PloS one 2013 :
Our results show that baicalein induced Epo and
VEGF expression in a HIF1a- and
PI3K/Akt dependent manner in neurons
Yang et al., Invest Ophthalmol Vis Sci 2009 (Anoxia...) :
Role of
PI3K/Akt and MEK/ERK in mediating hypoxia induced expression of HIF-1alpha and
VEGF in laser induced rat choroidal neovascularization ... A well established rat model of CNV and cultured human retinal pigment epithelium ( hRPE ) was used to investigate the
role of
PI3K/Akt and MEK/ERK pathways in regulating HIF-1alpha and
VEGF expression in CNV in rat and hRPE under hypoxia by immunohistochemistry, Western blot analysis, real-time PCR, and ELISA
Lee et al., Mol Pharmacol 2006 (Asthma...) :
This study aimed to determine the
effect of
PI3K inhibitors and PTEN on
VEGF expression in allergen induced airway inflammation
Lee et al., FEBS Lett 2010 :
We demonstrate that reduction in Ca ( 2+ ) by chelating compound BAPTA-AM or by IP ( 3 ) -endoplasmic reticulum blocker 2-APB selectively inhibited
VEGF induced activation of
c-Src-PI3K-Akt but not ERK1/2 in human coronary artery endothelial cells ( HCAEC ) ... We also show that the selective inhibitory effects of NADPH oxidase knockdown on
VEGF mediated
activation of
c-Src-PI3K-Akt signaling and cell proliferation in HCAEC can be reversed by increase in intracellular Ca ( 2+ )
Hellwig-Bürgel et al., Cell Physiol Biochem 2005 :
Thus,
PI3K signaling is
required for HIF-1alpha accumulation and
VEGF synthesis, whereas MAPKK-1 signaling is required for VEGF synthesis only
García-Maceira et al., Oncogene 2009 (Carcinoma, Hepatocellular) :
Moreover, silibinin reduced hypoxia induced
vascular endothelial growth factor ( VEGF ) release by HeLa and Hep3B cells, and this effect was
potentiated by the
PI3K/Akt inhibitor LY294002
Westra et al., Ann N Y Acad Sci 2009 (Arthritis, Rheumatoid) :
Protein and mRNA expression of HIF-1alpha and the
effects of inhibitors of the CaMKII-,
PI3K- , and ERK pathway on
VEGF and IL-6 production were analyzed
Chen et al., Mol Nutr Food Res 2012 :
Moreover, lycopene attenuated
VEGF receptor-2 (VEGFR2) mediated phosphorylation of extracellular signal regulated kinase ( ERK ), p38, and Akt as well as protein expression of
PI3K
Elayappan et al., Angiogenesis 2009 :
Of interest, PEDF effectively abrogated
VEGF mediated phosphorylation of
PI3K/Akt
Xu et al., PloS one 2012 (Liver Neoplasms) :
Addition of recombinant human
VEGF attenuated the inhibitory effects of PP on
PI3K/AKT pathway and the cancer phenotypes
Giuliani et al., Leukemia 2004 (Multiple Myeloma...) :
Moreover, we also found that the
PI3K kinase inhibitors, but not p38 MAPK inhibitors,
reduced VEGF secretion by myeloma cells and increase the inhibitory effect of MEK1 inhibitors
Tang et al., Mol Cancer Res 2006 (Breast Neoplasms...) :
Furthermore, the
PI3K-specific inhibitor LY294002
inhibited VEGF production by EMMPRIN overexpressing cells in a dose- and time dependent manner
Zhang et al., J Biol Chem 2003 :
Phosphorylation of VEGFR2 at Tyr-801 and Tyr-1175, the critical sites for
VEGF induced
PI3K-Akt signaling, was not involved in TNF mediated Akt activation ... Taken together, our data demonstrated that TNF induces transactivation between Etk and VEGFR2, and Etk directly activates
PI3K-Akt angiogenic signaling independent of
VEGF induced VEGFR2-PI3K-Akt signaling pathway
Lee et al., Mol Cells 2011 (Breast Neoplasms) :
Moreover, the higher production of
vascular endothelial growth factor ( VEGF ) in TAMR-MCF-7 cells was significantly
diminished by suppression of
PI3K or p38 kinase
Lu et al., Am J Respir Cell Mol Biol 2010 (Neovascularization, Pathologic...) :
Activation of
PI3K/Akt by bleomycin also
led to transcriptional activation and protein expression of hypoxia-inducible factor-1alpha ( HIF-1alpha ) and
vascular endothelial growth factor , which contributed to the fibroproliferative and collagen inducing effects of bleomycin
Kang et al., Oncogene 2008 (Neovascularization, Pathologic...) :
Our results show that N-myc plays an important role in the
PI3K mediated
VEGF regulation in NB cells
Li et al., Int J Mol Med 2006 :
Further, we found that
PI3K inhibitors, LY294002 and Wortmannin,
inhibited HIF-1alpha and
VEGF expression induced by UV radiation
Li et al., Zhongguo Dang Dai Er Ke Za Zhi 2011 (Neuroblastoma) :
The synthesis and secretion of
VEGF can be
inhibited by blocking TrkB-BDNF signal pathway with K252a or blocking the TrkB-BDNF downstream signal pathway
PI3K/Akt with LY294002
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
Piccolo et al., J Mol Med (Berl) 2013 (Breast Neoplasms...) :
Production of
VEGF , that was restored by exposure of silenced cells to recombinant LGALS3BP,
required an intact
PI3k/Akt signaling
Jang et al., BMC cancer 2010 (Breast Neoplasms...) :
Inhibition of
PI3K/Akt signaling by ANT2 shRNA
caused down-regulation of membrane-type 1 matrix metalloproteinase ( MT1-MMP ) and
vascular endothelial growth factor ( VEGF ) expression, decreased matrix metalloproteinase 2 (MMP2) and MMP9 activity, and suppressed migration and invasion of breast cancer cells
Jiang et al., Adv Cancer Res 2009 (Neoplasms...) :
PI3K signaling
regulates tumor growth and angiogenesis by activating AKT and other targets, and by inducing HIF-1 and
VEGF expression
Woods et al., Neuro Oncol 2002 (Astrocytoma...) :
Phosphatidylinositol 3'-kinase and MAPK/ERK kinase 1/2 differentially
regulate expression of
vascular endothelial growth factor in human malignant astrocytoma cells
Trisciuoglio et al., Mol Biol Cell 2005 (MAP Kinase Signaling System...) :
Involvement of
PI3K and MAPK signaling in bcl-2 induced
vascular endothelial growth factor expression in melanoma cells
Ruan et al., EMBO J 2012 :
Axl is essential for
VEGF-A dependent activation of
PI3K/Akt ... These results elucidate the mechanism by which
VEGF-A activates
PI3K/Akt , and identify previously unappreciated potential therapeutic targets of VEGF-A-driven processes
Yin et al., J Mol Med (Berl) 2011 (Disease Models, Animal...) :
PI3K inhibitor LY294002 significantly
attenuated Rg1 enhanced
VEGF expression and capillary density
Flaxenburg et al., J Immunol 2004 :
Also, wortmanin and a dominant-inhibitory mutant of
PI3K inhibited CD40 induced overexpression of
VEGF
Ghosh et al., J Biol Chem 2012 (MAP Kinase Signaling System...) :
Therefore, based on these observations, it is hypothesized that the
activation of
PI3K/AKT and p38 MAPK by
VEGF results in ETS-1 gene expression, which activates MMP-9 and MMP-13, leading to the invasion and scattering of SKOV-3 cells
Burroughs et al., Mol Cancer Res 2003 (MAP Kinase Signaling System) :
Mutation of the hypoxia response element ( HRE ), which mediates hypoxic stimulation of VEGF transcription, did not inhibit the effect of IGF-I on the VEGF promoter, despite the fact that this mutation inhibited
PI3-K stimulated
VEGF promoter activity in prostate cancer cells ... These data indicate that
PI3-K signaling does not
increase VEGF transcription through transactivation by HIF-1 at the HRE in normal PrEC
Huang et al., World J Gastroenterol 2004 (Carcinoma, Hepatocellular...) :
Effects of
PI3K and p42/p44 MAPK on overexpression of
vascular endothelial growth factor in hepatocellular carcinoma
Yu et al., Cancer Chemother Pharmacol 2011 (Carcinoma, Non-Small-Cell Lung...) :
The
PI3 K or ERK inhibitors also
attenuated expression of
VEGF and MMP-9
Poettler et al., Thromb Haemost 2012 :
Thus, VEGF165,
VEGF-E , FGF-2, EGF as well as HGF
induced a
PI3k dependent activation of pro-uPA when bound to uPAR, which led to an increase in cell surface fibrinolytic activity
Bhattacharya et al., J Neurooncol 2013 (Brain Neoplasms...) :
T11TS therapy in rodent glioma model significantly downregulated expression of
VEGF along with its receptor VEGFR-2 and
inhibited the expression of pro-survival
PI3K/Akt/eNOS proteins in glioma associated brain endothelial cells
Guo et al., Stroke 2009 :
In contrast, neither inhibition of GSK-3beta nor inhibition of
PI3-K had any detectable effects on
VEGF levels in astrocytes
Chetty et al., Int J Cancer 2010 (Lung Neoplasms) :
We also show that MMP-2 suppression disrupted
PI3K dependent
VEGF expression ; ectopic expression of myr-AKT restored VEGF inhibition
Dai et al., Oncogene 2009 :
In turn, OPN induced
VEGF activates
PI3K/AKT and the ERK1/2 pathway as a positive feedback signal
Genini et al., PloS one 2012 (Carcinoma, Non-Small-Cell Lung...) :
Induction of
VEGF was
due to both binding of PPARß/d to the VEGF promoter and
PI3K activation through a non-genomic mechanism
Wood et al., J Cell Biol 2006 :
In contrast, using both laser ablation and a novel wounding assay that allows localized treatment with inhibitory drugs, we show that
PI3K is essential for hemocyte chemotaxis toward wounds and that Pvf signals and
PDGF/VEGF receptor expression are not
required for this rapid chemotactic response