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- Publisher Website: 10.1073/pnas.1421697112
- Scopus: eid_2-s2.0-84920425095
- PMID: 25535357
- WOS: WOS:000347447100056
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Article: TAp73 suppresses tumor angiogenesis through repression of proangiogenic cytokines and HIF-1α activity
Title | TAp73 suppresses tumor angiogenesis through repression of proangiogenic cytokines and HIF-1α activity |
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Authors | |
Keywords | p73 Vascular permeability Angiogenesis HIF-1 alpha Tumor microenvironment |
Issue Date | 2015 |
Citation | Proceedings of the National Academy of Sciences of the United States of America, 2015, v. 112, n. 1, p. 220-225 How to Cite? |
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 αNp73 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. |
Persistent Identifier | http://hdl.handle.net/10722/292860 |
ISSN | 2023 Impact Factor: 9.4 2023 SCImago Journal Rankings: 3.737 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Stantic, Marina | - |
dc.contributor.author | Sakil, Habib A.M. | - |
dc.contributor.author | Zirath, Hanna | - |
dc.contributor.author | Fang, Trixy | - |
dc.contributor.author | Sanz, Gema | - |
dc.contributor.author | Fernandez-Woodbridge, Alejandro | - |
dc.contributor.author | Marin, Ana | - |
dc.contributor.author | Susanto, Evelyn | - |
dc.contributor.author | Mak, Tak W. | - |
dc.contributor.author | Henriksson, Marie Arsenian | - |
dc.contributor.author | Wilhelm, Margareta T. | - |
dc.date.accessioned | 2020-11-17T14:57:22Z | - |
dc.date.available | 2020-11-17T14:57:22Z | - |
dc.date.issued | 2015 | - |
dc.identifier.citation | Proceedings of the National Academy of Sciences of the United States of America, 2015, v. 112, n. 1, p. 220-225 | - |
dc.identifier.issn | 0027-8424 | - |
dc.identifier.uri | http://hdl.handle.net/10722/292860 | - |
dc.description.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 αNp73 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. | - |
dc.language | eng | - |
dc.relation.ispartof | Proceedings of the National Academy of Sciences of the United States of America | - |
dc.subject | p73 | - |
dc.subject | Vascular permeability | - |
dc.subject | Angiogenesis | - |
dc.subject | HIF-1 alpha | - |
dc.subject | Tumor microenvironment | - |
dc.title | TAp73 suppresses tumor angiogenesis through repression of proangiogenic cytokines and HIF-1α activity | - |
dc.type | Article | - |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.1073/pnas.1421697112 | - |
dc.identifier.pmid | 25535357 | - |
dc.identifier.pmcid | PMC4291634 | - |
dc.identifier.scopus | eid_2-s2.0-84920425095 | - |
dc.identifier.volume | 112 | - |
dc.identifier.issue | 1 | - |
dc.identifier.spage | 220 | - |
dc.identifier.epage | 225 | - |
dc.identifier.eissn | 1091-6490 | - |
dc.identifier.isi | WOS:000347447100056 | - |
dc.identifier.issnl | 0027-8424 | - |