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VEGFR2 pY949 signal...
VEGFR2 pY949 signalling regulates adherens junction integrity and metastatic spread
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- Li, Xiujuan (author)
- Uppsala University,Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi
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- Padhan, Narendra (author)
- Uppsala University,Uppsala universitet,Science for Life Laboratory, SciLifeLab,Vaskulärbiologi,Uppsala Univ, Sci Life Lab, Rudbeck Lab, Dept Immunol Genet & Pathol, S-75185 Uppsala, Sweden.
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- Sjöström, Elisabet O. (author)
- Uppsala University,Uppsala universitet,Vaskulärbiologi,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Sci Life Lab, Rudbeck Lab, Dept Immunol Genet & Pathol, S-75185 Uppsala, Sweden.
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- Roche, Francis P. (author)
- Uppsala University,Uppsala universitet,Vaskulärbiologi,Science for Life Laboratory, SciLifeLab
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- Testini, Chiara (author)
- Uppsala University,Uppsala universitet,Vaskulärbiologi,Science for Life Laboratory, SciLifeLab
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- Honkura, Naoki (author)
- Uppsala University,Uppsala universitet,Vaskulärbiologi,Science for Life Laboratory, SciLifeLab
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- Sainz-Jaspeado, Miguel (author)
- Uppsala University,Uppsala universitet,Vaskulärbiologi,Science for Life Laboratory, SciLifeLab
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- Gordon, Emma (author)
- Uppsala University,Uppsala universitet,Vaskulärbiologi,Science for Life Laboratory, SciLifeLab
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- Bentley, Katie (author)
- Uppsala University,Uppsala universitet,Vaskulärbiologi,Science for Life Laboratory, SciLifeLab,Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, 330 Brookline Ave, Boston, MA 02215 USA.
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- Philippides, Andrew (author)
- Univ Sussex, Ctr Computat Neurosci & Robot, Chichester 1 CI 104, Brighton BN1 9RH, E Sussex, England.,University of Sussex
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- Tolmachev, Vladimir (author)
- Uppsala universitet,Vaskulärbiologi,Science for Life Laboratory, SciLifeLab
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- Dejana, Elisabetta (author)
- Uppsala universitet,Vaskulärbiologi,Science for Life Laboratory, SciLifeLab,IFOM IEO Campus, Via Adamello 16, I-20139 Milan, Italy.
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- Stan, Radu V. (author)
- Dartmouth Coll, Dept Pathol, Geisel Sch Med Dartmouth, Lebanon, NH 03756 USA.
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- Vestweber, Dietmar (author)
- Max Planck Inst Mol Biomed, Dept Vasc Cell Biol, Rontgenstr 20, D-48149 Munster, Germany.
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- Ballmer-Hofer, Kurt (author)
- Paul Scherrer Inst, Biomol Res, Mol Cell Biol, CH-5232 Villigen, Switzerland.
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- Betsholtz, Christer (author)
- Karolinska Institutet,Uppsala universitet,Vaskulärbiologi,Science for Life Laboratory, SciLifeLab,Karolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, S-17177 Stockholm, Sweden.
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- Pietras, Kristian (author)
- Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Experimentell onkologi,Forskargrupper vid Lunds universitet,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Experimental oncology,Lund University Research Groups,Lund Univ, Medicon Village, Translat Canc Res, Bldg 404-A3, S-22381 Lund, Sweden.
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- Jansson, Leif (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Claesson-Welsh, Lena (author)
- Uppsala universitet,Vaskulärbiologi,Science for Life Laboratory, SciLifeLab
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(creator_code:org_t)
- 2016-03-23
- 2016
- English.
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
- Related links:
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https://doi.org/10.1...
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https://doi.org/10.1...
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Abstract
Subject headings
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- The specific role of VEGFA-induced permeability and vascular leakage in physiology and pathology has remained unclear. Here we show that VEGFA-induced vascular leakage depends on signalling initiated via the VEGFR2 phosphosite Y949, regulating dynamic c-Src and VE-cadherin phosphorylation. Abolished Y949 signalling in the mouse mutant Vegfr2(Y949F/Y949F) leads to VEGFA-resistant endothelial adherens junctions and a block in molecular extravasation. Vessels in Vegfr2(Y949F/Y949F) mice remain sensitive to inflammatory cytokines, and vascular morphology, blood pressure and flow parameters are normal. Tumour-bearing Vegfr2(Y949F/Y949F) mice display reduced vascular leakage and oedema, improved response to chemotherapy and, importantly, reduced metastatic spread. The inflammatory infiltration in the tumour micro-environment is unaffected. Blocking VEGFA-induced disassembly of endothelial junctions, thereby suppressing tumour oedema and metastatic spread, may be preferable to full vascular suppression in the treatment of certain cancer forms.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Li, Xiujuan
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Padhan, Narendra
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Sjöström, Elisab ...
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Roche, Francis P ...
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Testini, Chiara
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Honkura, Naoki
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show more...
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Sainz-Jaspeado, ...
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Gordon, Emma
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Bentley, Katie
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Philippides, And ...
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Tolmachev, Vladi ...
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Dejana, Elisabet ...
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Stan, Radu V.
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Vestweber, Dietm ...
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Ballmer-Hofer, K ...
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Betsholtz, Chris ...
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Pietras, Kristia ...
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Jansson, Leif
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Claesson-Welsh, ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
- Articles in the publication
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Nature Communica ...
- By the university
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Uppsala University
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Lund University
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Karolinska Institutet