Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1519670 (tumor angiogenesis)
 6,052 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human homologue of the Drosophila discs large tumor suppressor gene (hDlg) is a member of the membrane-associated guanylate kinase family with three PSD-95/Dlg/ZO-1 (PDZ) domains. hDlg has been shown to bind tumor suppressor proteins, adenomatous polyposis coli (APC) and protein tyrosine phosphatase and tensin homologue (PTEN), and several viral oncoproteins, and has been implicated in the negative regulation of cell proliferation. hDlg has furthermore been shown to localize at the plasma membrane of synapses and to scaffold cell surface receptors and channels. In epithelial cells, hDlg localizes at the basolateral plasma membrane, but its localization mechanism is unknown. We searched here for a transmembrane protein that directly bound to hDlg. hDlg bound tumor endothelial marker 5 (TEM5), a seven-pass transmembrane protein that is homologous to the family B of G-protein-coupled receptors (GPCRs). TEM5 has previously been reported to display elevated expression during tumor angiogenesis and neoangiogenesis. The PDZ domains of hDlg bound the C-terminal PDZ-binding motif of TEM5. The expression of TEM5 was detected in endothelial cells of embryonic liver, where hDlg colocalized with TEM5. hDlg furthermore bound a novel seven-pass transmembrane protein, which was homologous to TEM5, and was named here a TEM5-like protein (TEM5-like). These results suggest that hDlg localizes at the plasma membrane through TEM5 and TEM5-like and furthermore scaffolds these GPCRs in endothelial cells during tumor angiogenesis and neoangiogenesis.
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PMID:Direct binding of the human homologue of the Drosophila disc large tumor suppressor gene to seven-pass transmembrane proteins, tumor endothelial marker 5 (TEM5), and a novel TEM5-like protein. 1502 5

G protein-coupled receptor 124 (GPR124; also called tumor endothelial marker 5, TEM5) is highly expressed in tumor vasculature. While recent studies have revealed a role in vasculogenesis, evidence for GPR124 function in tumor angiogenesis is lacking. Here, we demonstrate that GPR124 is required for VEGF-induced tumor angiogenesis. GPR124 silencing in human endothelial cells inhibited mouse xenograft tumor angiogenic vessel formation and tumor growth. GPR124 regulated VEGF-induced tumor angiogenic processes in vitro including cell-cell interaction, permeability, migration, invasion, and tube formation. Therefore, GPR124 plays a key role in VEGF-induced tumor angiogenesis.
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PMID:G-protein coupled receptor 124 (GPR124) in endothelial cells regulates vascular endothelial growth factor (VEGF)-induced tumor angiogenesis. 2473 May 23