Nuclear Receptor COUP-TFII Controls Pancreatic Islet Tumor Angiogenesis by Regulating Vascular Endothelial Growth Factor/Vascular Endothelial Growth Factor Receptor-2 Signaling
Copyright policy )Nuclear Receptor COUP-TFII Controls Pancreatic Islet Tumor Angiogenesis by Regulating Vascular Endothelial Growth Factor/Vascular Endothelial Growth Factor Receptor-2 Signaling
Abstract 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. Cancer Res; 70(21); 8812–21. ©2010 AACR.
- Baylor College of Medicine United States
Male, Chromatin Immunoprecipitation, Integrases, Blotting, Western, GTPase-Activating Proteins, Infant, Newborn, Mice, Transgenic, COUP Transcription Factor II, Immunoenzyme Techniques, Mice, Cell Movement, Lymphatic Metastasis, Cell Adhesion, Animals, Humans, Female, Endothelium, Vascular, Endothelium, Lymphatic, Cells, Cultured, Cell Proliferation
Male, Chromatin Immunoprecipitation, Integrases, Blotting, Western, GTPase-Activating Proteins, Infant, Newborn, Mice, Transgenic, COUP Transcription Factor II, Immunoenzyme Techniques, Mice, Cell Movement, Lymphatic Metastasis, Cell Adhesion, Animals, Humans, Female, Endothelium, Vascular, Endothelium, Lymphatic, Cells, Cultured, Cell Proliferation
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).50 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!