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rdf:type |
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lifeskim:mentions |
umls-concept:C0022131,
umls-concept:C0037083,
umls-concept:C0078058,
umls-concept:C0081620,
umls-concept:C0206588,
umls-concept:C0378796,
umls-concept:C1171892,
umls-concept:C1417834,
umls-concept:C1519670,
umls-concept:C1710082,
umls-concept:C1998811,
umls-concept:C2587213,
umls-concept:C2698420
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pubmed:issue |
21
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pubmed:dateCreated |
2010-11-2
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pubmed:abstractText |
The significance of angiogenesis in cancer biology and therapy is well established. In this study, we used the prototypical RIP-Tag model of multistage pancreatic islet tumorigenesis to show that the nuclear receptor COUP-TFII is essential to regulate the balance between pro- and anti-angiogenic molecules that influence the angiogenic switch in cancer. Conditional ablation of COUP-TFII in the tumor microenvironment severely compromised neoangiogenesis and lymphangiogenesis during pancreatic tumor progression and metastasis. We found that COUP-TFII plays a cell-autonomous role in endothelial cells to control blood vessel sprouting by regulating cell proliferation and migration. Mechanistic investigations revealed that COUP-TFII suppressed vascular endothelial growth factor (VEGF)/VEGF receptor-2 (VEGFR-2) signaling by transcriptionally repressing the expression of VEGFR-1, thereby curtailing a central angiogenic driver of vascular growth. Taken together, our results implicate COUP-TFII as a critical factor in tumor angiogenesis through regulation of VEGF/VEGFR-2 signaling, suggesting COUP-TFII as a candidate target for antiangiogenic therapy.
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pubmed:grant |
http://linkedlifedata.com/resource/pubmed/grant/DK059820,
http://linkedlifedata.com/resource/pubmed/grant/DK45641,
http://linkedlifedata.com/resource/pubmed/grant/HD17379,
http://linkedlifedata.com/resource/pubmed/grant/HL076448,
http://linkedlifedata.com/resource/pubmed/grant/P01 DK059820-090003,
http://linkedlifedata.com/resource/pubmed/grant/R01 DK045641-18,
http://linkedlifedata.com/resource/pubmed/grant/R01 DK045641-19,
http://linkedlifedata.com/resource/pubmed/grant/R01 HL076448-03,
http://linkedlifedata.com/resource/pubmed/grant/R01 HL076448-04,
http://linkedlifedata.com/resource/pubmed/grant/R01 HL076448-05,
http://linkedlifedata.com/resource/pubmed/grant/R01 HL076448-06,
http://linkedlifedata.com/resource/pubmed/grant/R01 HL076448-07,
http://linkedlifedata.com/resource/pubmed/grant/R37 DK045641-16,
http://linkedlifedata.com/resource/pubmed/grant/R37 DK045641-17,
http://linkedlifedata.com/resource/pubmed/grant/R37 HD017379-19,
http://linkedlifedata.com/resource/pubmed/grant/R37 HD017379-20,
http://linkedlifedata.com/resource/pubmed/grant/R37 HD017379-21
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/COUP Transcription Factor II,
http://linkedlifedata.com/resource/pubmed/chemical/Cre recombinase,
http://linkedlifedata.com/resource/pubmed/chemical/GTPase-Activating Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Gt(ROSA)26Sor protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Integrases,
http://linkedlifedata.com/resource/pubmed/chemical/Nr2f2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Ralbp1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor...,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor...,
http://linkedlifedata.com/resource/pubmed/chemical/vascular endothelial growth factor...
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1538-7445
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pubmed:author |
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pubmed:copyrightInfo |
©2010 AACR.
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
70
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
8812-21
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pubmed:dateRevised |
2011-11-1
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pubmed:meshHeading |
pubmed-meshheading:20978203-Animals,
pubmed-meshheading:20978203-Blotting, Western,
pubmed-meshheading:20978203-COUP Transcription Factor II,
pubmed-meshheading:20978203-Cell Adhesion,
pubmed-meshheading:20978203-Cell Movement,
pubmed-meshheading:20978203-Cell Proliferation,
pubmed-meshheading:20978203-Cells, Cultured,
pubmed-meshheading:20978203-Chromatin Immunoprecipitation,
pubmed-meshheading:20978203-Endothelium, Lymphatic,
pubmed-meshheading:20978203-Endothelium, Vascular,
pubmed-meshheading:20978203-Female,
pubmed-meshheading:20978203-GTPase-Activating Proteins,
pubmed-meshheading:20978203-Humans,
pubmed-meshheading:20978203-Immunoenzyme Techniques,
pubmed-meshheading:20978203-Infant, Newborn,
pubmed-meshheading:20978203-Integrases,
pubmed-meshheading:20978203-Lymphatic Metastasis,
pubmed-meshheading:20978203-Male,
pubmed-meshheading:20978203-Mice,
pubmed-meshheading:20978203-Mice, Transgenic,
pubmed-meshheading:20978203-Neovascularization, Pathologic,
pubmed-meshheading:20978203-Pancreatic Neoplasms,
pubmed-meshheading:20978203-Proteins,
pubmed-meshheading:20978203-RNA, Messenger,
pubmed-meshheading:20978203-RNA, Small Interfering,
pubmed-meshheading:20978203-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:20978203-Signal Transduction,
pubmed-meshheading:20978203-Umbilical Veins,
pubmed-meshheading:20978203-Vascular Endothelial Growth Factor A,
pubmed-meshheading:20978203-Vascular Endothelial Growth Factor Receptor-1,
pubmed-meshheading:20978203-Vascular Endothelial Growth Factor Receptor-2
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pubmed:year |
2010
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pubmed:articleTitle |
Nuclear receptor COUP-TFII controls pancreatic islet tumor angiogenesis by regulating vascular endothelial growth factor/vascular endothelial growth factor receptor-2 signaling.
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