TAp73 suppresses tumor angiogenesis through repression of proangiogenic cytokines and HIF-1α activity.
Proc Natl Acad Sci U S A
; 112(1): 220-5, 2015 Jan 06.
Article
em En
| MEDLINE
| ID: mdl-25535357
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Proteínas Nucleares
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Citocinas
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Proteínas Supressoras de Tumor
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Indutores da Angiogênese
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Proteínas de Ligação a DNA
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Subunidade alfa do Fator 1 Induzível por Hipóxia
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Neovascularização Patológica
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article