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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">E2F1 promotes angiogenesis through the VEGF-C/VEGFR-3 axis in a feedback loop for cooperative induction of PDGF-B</title><author><name sortKey="Engelmann, David" sort="Engelmann, David" uniqKey="Engelmann D" first="David" last="Engelmann">David Engelmann</name><affiliation><nlm:aff id="af1"><addr-line>Institute of Experimental Gene Therapy and Cancer Research</addr-line>,<institution>Rostock University Medical Center</institution>,<addr-line>18057 Rostock</addr-line>,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Mayoli Nussle, Deborah" sort="Mayoli Nussle, Deborah" uniqKey="Mayoli Nussle D" first="Deborah" last="Mayoli-Nüssle">Deborah Mayoli-Nüssle</name><affiliation><nlm:aff id="af1"><addr-line>Institute of Experimental Gene Therapy and Cancer Research</addr-line>,<institution>Rostock University Medical Center</institution>,<addr-line>18057 Rostock</addr-line>,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Mayrhofer, Christian" sort="Mayrhofer, Christian" uniqKey="Mayrhofer C" first="Christian" last="Mayrhofer">Christian Mayrhofer</name><affiliation><nlm:aff id="af2"><addr-line>Institute for Experimental Surgery</addr-line>,<institution>Rostock University Medical Center</institution>,<addr-line>18057 Rostock</addr-line>,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Furst, Katharina" sort="Furst, Katharina" uniqKey="Furst K" first="Katharina" last="Fürst">Katharina Fürst</name><affiliation><nlm:aff id="af1"><addr-line>Institute of Experimental Gene Therapy and Cancer Research</addr-line>,<institution>Rostock University Medical Center</institution>,<addr-line>18057 Rostock</addr-line>,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Alla, Vijay" sort="Alla, Vijay" uniqKey="Alla V" first="Vijay" last="Alla">Vijay Alla</name><affiliation><nlm:aff id="af1"><addr-line>Institute of Experimental Gene Therapy and Cancer Research</addr-line>,<institution>Rostock University Medical Center</institution>,<addr-line>18057 Rostock</addr-line>,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Stoll, Anja" sort="Stoll, Anja" uniqKey="Stoll A" first="Anja" last="Stoll">Anja Stoll</name><affiliation><nlm:aff id="af1"><addr-line>Institute of Experimental Gene Therapy and Cancer Research</addr-line>,<institution>Rostock University Medical Center</institution>,<addr-line>18057 Rostock</addr-line>,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Spitschak, Alf" sort="Spitschak, Alf" uniqKey="Spitschak A" first="Alf" last="Spitschak">Alf Spitschak</name><affiliation><nlm:aff id="af1"><addr-line>Institute of Experimental Gene Therapy and Cancer Research</addr-line>,<institution>Rostock University Medical Center</institution>,<addr-line>18057 Rostock</addr-line>,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Abshagen, Kerstin" sort="Abshagen, Kerstin" uniqKey="Abshagen K" first="Kerstin" last="Abshagen">Kerstin Abshagen</name><affiliation><nlm:aff id="af2"><addr-line>Institute for Experimental Surgery</addr-line>,<institution>Rostock University Medical Center</institution>,<addr-line>18057 Rostock</addr-line>,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Vollmar, Brigitte" sort="Vollmar, Brigitte" uniqKey="Vollmar B" first="Brigitte" last="Vollmar">Brigitte Vollmar</name><affiliation><nlm:aff id="af2"><addr-line>Institute for Experimental Surgery</addr-line>,<institution>Rostock University Medical Center</institution>,<addr-line>18057 Rostock</addr-line>,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Ran, Sophia" sort="Ran, Sophia" uniqKey="Ran S" first="Sophia" last="Ran">Sophia Ran</name><affiliation><nlm:aff id="af3"><addr-line>Department of Medical Microbiology, Immunology and Cell Biology</addr-line>,<institution>Southern Illinois University School of Medicine</institution>,<addr-line>Springfield, IL 62794-9626</addr-line>,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Putzer, Brigitte M" sort="Putzer, Brigitte M" uniqKey="Putzer B" first="Brigitte M." last="Pützer">Brigitte M. Pützer</name><affiliation><nlm:aff id="af1"><addr-line>Institute of Experimental Gene Therapy and Cancer Research</addr-line>,<institution>Rostock University Medical Center</institution>,<addr-line>18057 Rostock</addr-line>,<country>Germany</country></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24014887</idno><idno type="pmc">3888194</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3888194</idno><idno type="RBID">PMC:3888194</idno><idno type="doi">10.1093/jmcb/mjt035</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">002F60</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002F60</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">E2F1 promotes angiogenesis through the VEGF-C/VEGFR-3 axis in a feedback loop for cooperative induction of PDGF-B</title><author><name sortKey="Engelmann, David" sort="Engelmann, David" uniqKey="Engelmann D" first="David" last="Engelmann">David Engelmann</name><affiliation><nlm:aff id="af1"><addr-line>Institute of Experimental Gene Therapy and Cancer Research</addr-line>,<institution>Rostock University Medical Center</institution>,<addr-line>18057 Rostock</addr-line>,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Mayoli Nussle, Deborah" sort="Mayoli Nussle, Deborah" uniqKey="Mayoli Nussle D" first="Deborah" last="Mayoli-Nüssle">Deborah Mayoli-Nüssle</name><affiliation><nlm:aff id="af1"><addr-line>Institute of Experimental Gene Therapy and Cancer Research</addr-line>,<institution>Rostock University Medical Center</institution>,<addr-line>18057 Rostock</addr-line>,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Mayrhofer, Christian" sort="Mayrhofer, Christian" uniqKey="Mayrhofer C" first="Christian" last="Mayrhofer">Christian Mayrhofer</name><affiliation><nlm:aff id="af2"><addr-line>Institute for Experimental Surgery</addr-line>,<institution>Rostock University Medical Center</institution>,<addr-line>18057 Rostock</addr-line>,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Furst, Katharina" sort="Furst, Katharina" uniqKey="Furst K" first="Katharina" last="Fürst">Katharina Fürst</name><affiliation><nlm:aff id="af1"><addr-line>Institute of Experimental Gene Therapy and Cancer Research</addr-line>,<institution>Rostock University Medical Center</institution>,<addr-line>18057 Rostock</addr-line>,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Alla, Vijay" sort="Alla, Vijay" uniqKey="Alla V" first="Vijay" last="Alla">Vijay Alla</name><affiliation><nlm:aff id="af1"><addr-line>Institute of Experimental Gene Therapy and Cancer Research</addr-line>,<institution>Rostock University Medical Center</institution>,<addr-line>18057 Rostock</addr-line>,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Stoll, Anja" sort="Stoll, Anja" uniqKey="Stoll A" first="Anja" last="Stoll">Anja Stoll</name><affiliation><nlm:aff id="af1"><addr-line>Institute of Experimental Gene Therapy and Cancer Research</addr-line>,<institution>Rostock University Medical Center</institution>,<addr-line>18057 Rostock</addr-line>,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Spitschak, Alf" sort="Spitschak, Alf" uniqKey="Spitschak A" first="Alf" last="Spitschak">Alf Spitschak</name><affiliation><nlm:aff id="af1"><addr-line>Institute of Experimental Gene Therapy and Cancer Research</addr-line>,<institution>Rostock University Medical Center</institution>,<addr-line>18057 Rostock</addr-line>,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Abshagen, Kerstin" sort="Abshagen, Kerstin" uniqKey="Abshagen K" first="Kerstin" last="Abshagen">Kerstin Abshagen</name><affiliation><nlm:aff id="af2"><addr-line>Institute for Experimental Surgery</addr-line>,<institution>Rostock University Medical Center</institution>,<addr-line>18057 Rostock</addr-line>,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Vollmar, Brigitte" sort="Vollmar, Brigitte" uniqKey="Vollmar B" first="Brigitte" last="Vollmar">Brigitte Vollmar</name><affiliation><nlm:aff id="af2"><addr-line>Institute for Experimental Surgery</addr-line>,<institution>Rostock University Medical Center</institution>,<addr-line>18057 Rostock</addr-line>,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Ran, Sophia" sort="Ran, Sophia" uniqKey="Ran S" first="Sophia" last="Ran">Sophia Ran</name><affiliation><nlm:aff id="af3"><addr-line>Department of Medical Microbiology, Immunology and Cell Biology</addr-line>,<institution>Southern Illinois University School of Medicine</institution>,<addr-line>Springfield, IL 62794-9626</addr-line>,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Putzer, Brigitte M" sort="Putzer, Brigitte M" uniqKey="Putzer B" first="Brigitte M." last="Pützer">Brigitte M. Pützer</name><affiliation><nlm:aff id="af1"><addr-line>Institute of Experimental Gene Therapy and Cancer Research</addr-line>,<institution>Rostock University Medical Center</institution>,<addr-line>18057 Rostock</addr-line>,<country>Germany</country></nlm:aff></affiliation></author></analytic><series><title level="j">Journal of Molecular Cell Biology</title><idno type="ISSN">1674-2788</idno><idno type="eISSN">1759-4685</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Angiogenesis is essential for primary tumor growth and metastatic dissemination. E2F1, frequently upregulated in advanced cancers, was recently shown to drive malignant progression. In an attempt to decipher the molecular events underlying this behavior, we demonstrate that the tumor cell-associated vascular endothelial growth factor-C/receptor-3 (VEGF-C/VEGFR-3) axis is controlled by E2F1. Activation or forced expression of E2F1 in cancer cells leads to the upregulation of VEGFR-3 and its ligand VEGF-C, whereas E2F1 depletion prevents their expression. E2F1-dependent receptor induction is crucial for tumor cells to enhance formation of capillary tubes and neovascularization in mice. We further provide evidence for a positive feedback loop between E2F1 and VEGFR-3 signaling to stimulate pro-angiogenic platelet-derived growth factor B (PDGF-B). E2F1 or VEGFR-3 knockdown results in reduced PDGF-B levels, while the coexpression synergistically upregulates promoter activity and endogenous protein expression of PDGF-B. Our findings delineate an as yet unrecognized function of E2F1 as enhancer of angiogenesis via regulation of VEGF-C/VEGFR-3 signaling in tumors to cooperatively activate PDGF-B expression. Targeting this pathway might be reasonable to complement standard anti-angiogenic treatment of cancers with deregulated E2F1.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Mol Cell Biol</journal-id><journal-id journal-id-type="iso-abbrev">J Mol Cell Biol</journal-id><journal-id journal-id-type="publisher-id">jmcb</journal-id><journal-id journal-id-type="hwp">jmcb</journal-id><journal-title-group><journal-title>Journal of Molecular Cell Biology</journal-title></journal-title-group><issn pub-type="ppub">1674-2788</issn><issn pub-type="epub">1759-4685</issn><publisher><publisher-name>Oxford University Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">24014887</article-id><article-id pub-id-type="pmc">3888194</article-id><article-id pub-id-type="doi">10.1093/jmcb/mjt035</article-id><article-id pub-id-type="publisher-id">mjt035</article-id><article-categories><subj-group subj-group-type="heading"><subject>Articles</subject></subj-group></article-categories><title-group><article-title>E2F1 promotes angiogenesis through the VEGF-C/VEGFR-3 axis in a feedback loop for cooperative induction of PDGF-B</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Engelmann</surname><given-names>David</given-names></name><xref ref-type="aff" rid="af1">1</xref><xref ref-type="author-notes" rid="AN1">†</xref></contrib><contrib contrib-type="author"><name><surname>Mayoli-Nüssle</surname><given-names>Deborah</given-names></name><xref ref-type="aff" rid="af1">1</xref><xref ref-type="author-notes" rid="AN1">†</xref></contrib><contrib contrib-type="author"><name><surname>Mayrhofer</surname><given-names>Christian</given-names></name><xref ref-type="aff" rid="af2">2</xref></contrib><contrib contrib-type="author"><name><surname>Fürst</surname><given-names>Katharina</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Alla</surname><given-names>Vijay</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Stoll</surname><given-names>Anja</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Spitschak</surname><given-names>Alf</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Abshagen</surname><given-names>Kerstin</given-names></name><xref ref-type="aff" rid="af2">2</xref></contrib><contrib contrib-type="author"><name><surname>Vollmar</surname><given-names>Brigitte</given-names></name><xref ref-type="aff" rid="af2">2</xref></contrib><contrib contrib-type="author"><name><surname>Ran</surname><given-names>Sophia</given-names></name><xref ref-type="aff" rid="af3">3</xref></contrib><contrib contrib-type="author"><name><surname>Pützer</surname><given-names>Brigitte M.</given-names></name><xref ref-type="aff" rid="af1">1</xref><xref ref-type="corresp" rid="cor1">*</xref></contrib></contrib-group><aff id="af1"><label>1</label><addr-line>Institute of Experimental Gene Therapy and Cancer Research</addr-line>,<institution>Rostock University Medical Center</institution>,<addr-line>18057 Rostock</addr-line>,<country>Germany</country></aff><aff id="af2"><label>2</label><addr-line>Institute for Experimental Surgery</addr-line>,<institution>Rostock University Medical Center</institution>,<addr-line>18057 Rostock</addr-line>,<country>Germany</country></aff><aff id="af3"><label>3</label><addr-line>Department of Medical Microbiology, Immunology and Cell Biology</addr-line>,<institution>Southern Illinois University School of Medicine</institution>,<addr-line>Springfield, IL 62794-9626</addr-line>,<country>USA</country></aff><author-notes><fn id="AN1"><label>†</label><p>These authors contributed equally to this work.</p></fn><corresp id="cor1"><label>*</label>Correspondence to: Brigitte M. Pützer, E-mail: <email>brigitte.puetzer@med.uni-rostock.de</email></corresp></author-notes><pub-date pub-type="ppub"><month>12</month><year>2013</year></pub-date><pub-date pub-type="epub"><day>6</day><month>9</month><year>2013</year></pub-date><pub-date pub-type="pmc-release"><day>1</day><month>12</month><year>2014</year></pub-date><pmc-comment> PMC Release delay is 12 months and
0 days and was based on the
<volume>5</volume><issue>6</issue><issue-title>Collection: Cell Signaling for Pathological Responses</issue-title><fpage>391</fpage><lpage>403</lpage><history><date date-type="received"><day>10</day><month>5</month><year>2013</year></date><date date-type="rev-recd"><day>4</day><month>7</month><year>2013</year></date><date date-type="accepted"><day>16</day><month>7</month><year>2013</year></date></history><permissions><copyright-statement>© The Author (2013). Published by Oxford University Press on behalf of <italic>Journal of Molecular Cell Biology</italic>, IBCB, SIBS, CAS. All rights reserved.</copyright-statement><copyright-year>2013</copyright-year></permissions><self-uri content-type="pdf" xlink:type="simple" xlink:href="mjt035.pdf"></self-uri><abstract><p>Angiogenesis is essential for primary tumor growth and metastatic dissemination. E2F1, frequently upregulated in advanced cancers, was recently shown to drive malignant progression. In an attempt to decipher the molecular events underlying this behavior, we demonstrate that the tumor cell-associated vascular endothelial growth factor-C/receptor-3 (VEGF-C/VEGFR-3) axis is controlled by E2F1. Activation or forced expression of E2F1 in cancer cells leads to the upregulation of VEGFR-3 and its ligand VEGF-C, whereas E2F1 depletion prevents their expression. E2F1-dependent receptor induction is crucial for tumor cells to enhance formation of capillary tubes and neovascularization in mice. We further provide evidence for a positive feedback loop between E2F1 and VEGFR-3 signaling to stimulate pro-angiogenic platelet-derived growth factor B (PDGF-B). E2F1 or VEGFR-3 knockdown results in reduced PDGF-B levels, while the coexpression synergistically upregulates promoter activity and endogenous protein expression of PDGF-B. Our findings delineate an as yet unrecognized function of E2F1 as enhancer of angiogenesis via regulation of VEGF-C/VEGFR-3 signaling in tumors to cooperatively activate PDGF-B expression. Targeting this pathway might be reasonable to complement standard anti-angiogenic treatment of cancers with deregulated E2F1.</p></abstract><kwd-group><kwd>E2F1</kwd><kwd>hypoxia</kwd><kwd>neovascularization</kwd><kwd>PDGF-B</kwd><kwd>VEGFR-3</kwd><kwd>VEGF-C</kwd><kwd>regulatory feedback loop</kwd></kwd-group><counts><page-count count="13"></page-count></counts></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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