| First Author | Qin J | Year | 2010 |
| Journal | Cancer Res | Volume | 70 |
| Issue | 21 | Pages | 8812-21 |
| PubMed ID | 20978203 | Mgi Jnum | J:166214 |
| Mgi Id | MGI:4840125 | Doi | 10.1158/0008-5472.CAN-10-0551 |
| Citation | Qin J, et al. (2010) Nuclear receptor COUP-TFII controls pancreatic islet tumor angiogenesis by regulating vascular endothelial growth factor/vascular endothelial growth factor receptor-2 signaling. Cancer Res 70(21):8812-21 |
| 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. |
