TAp73 suppresses tumor angiogenesis through repression of proangiogenic cytokines and HIF-1 alpha activity

Stantic Marina; Sakil Habib A. M.; Zirath HannaFang TrixySanz GemaFernandez-Woodbridge AlejandroMarin AnaSusanto EvelynMak Tak W.Henriksson Marie ArsenianWilhelm Margareta T.

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TAp73 suppresses tumor angiogenesis through repression of proangiogenic cytokines and HIF-1 alpha activity

机译：TAp73 suppresses tumor angiogenesis through repression of proangiogenic cytokines and HIF-1 alpha activity

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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 Delta Np73 leads to reduced blood vessel formation in tumors. Furthermore, we show that up-regulated Delta Np73 levels are associated with increased angiogenesis in human breast cancer and that inhibition of TAp73 results in an accumulation of HIF-1 alpha and up-regulation of HIF-1 Delta target genes. Taken together, our data demonstrate that loss of TAp73 or Delta Np73 up-regulation activates the angiogenic switch that stimulates tumor growth and progression.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2015年第1期|220-225|共6页
作者
Stantic Marina; Sakil Habib A. M.; Zirath HannaFang TrixySanz GemaFernandez-Woodbridge AlejandroMarin AnaSusanto EvelynMak Tak W.Henriksson Marie ArsenianWilhelm Margareta T.;
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作者单位

Karolinska Inst, Dept Microbiol Tumor & Cell Biol, S-17177 Stockholm, Sweden;

Univ Hlth Network, Ontario Canc Inst, Campbell Family Canc Res Inst, Toronto, ON M5G 2C1, Canada;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
p73; angiogenesis; HIF-1 alpha; tumor microenvironment; vascular permeability;

TAp73 suppresses tumor angiogenesis through repression of proangiogenic cytokines and HIF-1 alpha activity

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