| First Author | Stantic M | Year | 2015 |
| Journal | Proc Natl Acad Sci U S A | Volume | 112 |
| Issue | 1 | Pages | 220-5 |
| PubMed ID | 25535357 | Mgi Jnum | J:218244 |
| Mgi Id | MGI:5617074 | Doi | 10.1073/pnas.1421697112 |
| Citation | Stantic M, et al. (2015) TAp73 suppresses tumor angiogenesis through repression of proangiogenic cytokines and HIF-1alpha activity. Proc Natl Acad Sci U S A 112(1):220-5 |
| abstractText | The p53-family member TAp73 is known to function as a tumor suppressor and regulates genomic integrity, cellular proliferation, and apoptosis; however, its role in tumor angiogenesis is poorly understood. Here we demonstrate that TAp73 regulates tumor angiogenesis through repression of proangiogenic and proinflammatory cytokines. Importantly, loss of TAp73 results in highly vascularized tumors, as well as an increase in vessel permeability resulting from disruption of vascular endothelial-cadherin junctions between endothelial cells. In contrast, loss of the oncogenic p73 isoform DeltaNp73 leads to reduced blood vessel formation in tumors. Furthermore, we show that up-regulated DeltaNp73 levels are associated with increased angiogenesis in human breast cancer and that inhibition of TAp73 results in an accumulation of HIF-1alpha and up-regulation of HIF-1alpha target genes. Taken together, our data demonstrate that loss of TAp73 or DeltaNp73 up-regulation activates the angiogenic switch that stimulates tumor growth and progression. |
