TAp73 suppresses tumor angiogenesis through repression of proangiogenic cytokines and HIF-1α activity
| Autor: | Marina Stantic, Tak W. Mak, Evelyn Susanto, Margareta Wilhelm, Ana Marin, Marie Henriksson, Trixy Fang, Habib A. M. Sakil, Hanna Zirath, Alejandro Fernandez-Woodbridge, Gema Sanz |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Angiogenic Switch
Angiogenesis Neovascularization Physiologic Vascular permeability Breast Neoplasms Biology Permeability Proinflammatory cytokine Mice Animals Humans Protein Isoforms Tumor Protein p73 Zebrafish Cell Line Transformed Cell Proliferation Inflammation Tumor microenvironment Multidisciplinary Neovascularization Pathologic Tumor Suppressor Proteins Endothelial Cells Nuclear Proteins Biological Sciences Cadherins Hypoxia-Inducible Factor 1 alpha Subunit Cell Hypoxia Cell biology DNA-Binding Proteins HIF1A Gene Expression Regulation Cytokines Angiogenesis Inducing Agents Female |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 112(1) |
| ISSN: | 1091-6490 |
| Popis: | 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 ΔNp73 leads to reduced blood vessel formation in tumors. Furthermore, we show that up-regulated ΔNp73 levels are associated with increased angiogenesis in human breast cancer and that inhibition of TAp73 results in an accumulation of HIF-1α and up-regulation of HIF-1α target genes. Taken together, our data demonstrate that loss of TAp73 or ΔNp73 up-regulation activates the angiogenic switch that stimulates tumor growth and progression. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|