We have a suspicion that you are an automated web bot software, not a real user. To keep our site fast for other users, we have slowed down this page. The slowdown will gradually disappear. If you think this is a mistake, please contact us at genome-www@soe.ucsc.edu. Also note that all data for hgGeneGraph can be obtained through our public MySQL server and all our software source code is available and can be installed locally onto your own computer. If you are unsure how to use these resources, do not hesitate to contact us.
UCSC Genome Browser Gene Interaction Graph
Gene interactions and pathways from curated databases and text-mining
Mol Cancer Res 2006, PMID: 16778084

Regulation of vascular endothelial growth factor expression by EMMPRIN via the PI3K-Akt signaling pathway.

Tang, Yi; Nakada, Marian T; Rafferty, Patricia; Laraio, Jenny; McCabe, Francis L; Millar, Hillary; Cunningham, Mark; Snyder, Linda A; Bugelski, Peter; Yan, Li

Extracellular matrix metalloproteinase (MMP) inducer (EMMPRIN) is a cell surface glycoprotein overexpressed in many solid tumors. In addition to its ability to stimulate stromal MMP expression, tumor-associated EMMPRIN also induces vascular endothelial growth factor (VEGF) expression. To explore the underlying signaling pathways used by EMMPRIN, we studied the involvement of phosphoinositide 3-kinase (PI3K)-Akt, mitogen-activated protein kinase (MAPK), JUN, and p38 kinases in EMMPRIN-mediated VEGF regulation. Overexpression of EMMPRIN in MDA-MB-231 breast cancer cells stimulated the phosphorylation of only Akt and MAPKs but not that of JUN and p38 kinases. Conversely, inhibition of EMMPRIN expression resulted in suppressed Akt and MAPK phosphorylation. Furthermore, the PI3K-specific inhibitor LY294002 inhibited VEGF production by EMMPRIN-overexpressing cells in a dose- and time-dependent manner. On the other hand, the MAPK inhibitor U0126 did not affect VEGF production. In vivo, EMMPRIN-overexpressing tumors with elevated VEGF expression had a high level of phosphorylation of Akt and MAPK. Finally, when fibroblast cells were treated with recombinant EMMPRIN, Akt kinase but not MAPK was phosphorylated concomitant with an increase in VEGF production. Both the activation of Akt kinase and the induction of VEGF were specifically inhibited with a neutralizing antibody to EMMPRIN. Our results show that in both tumor and fibroblast cells EMMPRIN regulates VEGF production via the PI3K-Akt pathway but not via the MAPK, JUN, or p38 kinase pathways.

Diseases/Pathways annotated by Medline MESH: Breast Neoplasms, Neoplasms, Neovascularization, Pathologic
Document information provided by NCBI PubMed

Text Mining Data

vascular endothelial growth factor — EMMPRIN: " Regulation of vascular endothelial growth factor expression by EMMPRIN via the PI3K-Akt signaling pathway "

EMMPRIN → vascular endothelial growth factor: " In addition to its ability to stimulate stromal MMP expression, tumor associated EMMPRIN also induces vascular endothelial growth factor ( VEGF ) expression "

VEGF → EMMPRIN: " To explore the underlying signaling pathways used by EMMPRIN, we studied the involvement of phosphoinositide 3-kinase (PI3K)-Akt, mitogen activated protein kinase ( MAPK ), JUN, and p38 kinases in EMMPRIN mediated VEGF regulation "

VEGF — mitogen activated protein kinase: " To explore the underlying signaling pathways used by EMMPRIN, we studied the involvement of phosphoinositide 3-kinase (PI3K)-Akt, mitogen activated protein kinase ( MAPK ), JUN, and p38 kinases in EMMPRIN mediated VEGF regulation "

VEGF — (PI3K)-Akt: " To explore the underlying signaling pathways used by EMMPRIN, we studied the involvement of phosphoinositide 3-kinase (PI3K)-Akt , mitogen activated protein kinase ( MAPK ), JUN, and p38 kinases in EMMPRIN mediated VEGF regulation "

VEGF — JUN: " To explore the underlying signaling pathways used by EMMPRIN, we studied the involvement of phosphoinositide 3-kinase (PI3K)-Akt, mitogen activated protein kinase ( MAPK ), JUN , and p38 kinases in EMMPRIN mediated VEGF regulation "

VEGF — phosphoinositide 3-kinase (PI3K)-Akt: " To explore the underlying signaling pathways used by EMMPRIN, we studied the involvement of phosphoinositide 3-kinase (PI3K)-Akt , mitogen activated protein kinase ( MAPK ), JUN, and p38 kinases in EMMPRIN mediated VEGF regulation "

Akt ⊣ EMMPRIN: " Overexpression of EMMPRIN in MDA-MB-231 breast cancer cells stimulated the phosphorylation of only Akt and MAPKs but not that of JUN and p38 kinases "

MAPK ⊣ EMMPRIN: " Conversely, inhibition of EMMPRIN expression resulted in suppressed Akt and MAPK phosphorylation "

Akt ⊣ EMMPRIN: " Conversely, inhibition of EMMPRIN expression resulted in suppressed Akt and MAPK phosphorylation "

VEGF → PI3K-specific: " Furthermore, the PI3K-specific inhibitor LY294002 inhibited VEGF production by EMMPRIN overexpressing cells in a dose- and time dependent manner "

VEGF → EMMPRIN: " Our results show that in both tumor and fibroblast cells EMMPRIN regulates VEGF production via the PI3K-Akt pathway but not via the MAPK, JUN, or p38 kinase pathways "

Manually curated Databases

No curated data.