eprintid: 1431161
rev_number: 43
eprint_status: archive
userid: 608
dir: disk0/01/43/11/61
datestamp: 2014-06-02 18:47:43
lastmod: 2021-10-21 00:08:16
status_changed: 2016-04-15 11:20:17
type: article
metadata_visibility: show
item_issues_count: 0
creators_name: Raimondi, C
creators_name: Fantin, A
creators_name: Lampropoulou, A
creators_name: Denti, L
creators_name: Chikh, A
creators_name: Ruhrberg, C
title: Imatinib inhibits VEGF-independent angiogenesis by targeting neuropilin 1-dependent ABL1 activation in endothelial cells
ispublished: pub
divisions: UCL
divisions: B02
divisions: C07
divisions: D08
keywords: Animals, Benzamides, Cell Adhesion, Cell Movement, Cells, Cultured, Endothelial Cells, Enzyme Activation, Fibronectins, Humans, Imatinib Mesylate, Immunoblotting, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Microscopy, Confocal, Neovascularization, Physiologic, Neuropilin-1, Paxillin, Phosphorylation, Piperazines, Protein Kinase Inhibitors, Proto-Oncogene Proteins c-abl, Pyrimidines, RNA Interference, Retinal Neovascularization, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factor Receptor-2
note: Copyright © 2014 Raimondi et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
abstract: To enable new blood vessel growth, endothelial cells (ECs) express neuropilin 1 (NRP1), and NRP1 associates with the receptor tyrosine kinase VEGFR2 after binding the vascular endothelial growth factor A (VEGF) to enhance arteriogenesis. We report that NRP1 contributes to angiogenesis through a novel mechanism. In human and mouse ECs, the integrin ligand fibronectin (FN) stimulated actin remodeling and phosphorylation of the focal adhesion component paxillin (PXN) in a VEGF/VEGFR2-independent but NRP1-dependent manner. NRP1 formed a complex with ABL1 that was responsible for FN-dependent PXN activation and actin remodeling. This complex promoted EC motility in vitro and during angiogenesis on FN substrates in vivo. Accordingly, both physiological and pathological angiogenesis in the retina were inhibited by treatment with Imatinib, a small molecule inhibitor of ABL1 which is widely used to prevent the proliferation of tumor cells that express BCR-ABL fusion proteins. The finding that NRP1 regulates angiogenesis in a VEGF- and VEGFR2-independent fashion via ABL1 suggests that ABL1 inhibition provides a novel opportunity for anti-angiogenic therapy to complement VEGF or VEGFR2 blockade in eye disease or solid tumor growth.
date: 2014-06-02
official_url: http://dx.doi.org/10.1084/jem.20132330
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
article_type_text: Journal Article
verified: verified_manual
elements_source: PubMed
elements_id: 949568
doi: 10.1084/jem.20132330
pii: jem.20132330
lyricists_name: Denti, Laura
lyricists_name: Fantin, Alessandro
lyricists_name: Lampropoulou, Anastasia-Syrmalenia
lyricists_name: Raimondi, Claudio
lyricists_name: Ruhrberg, Christiana
lyricists_id: LDENT76
lyricists_id: AFANT57
lyricists_id: ALAMP16
lyricists_id: CRAIM84
lyricists_id: CRUHR98
full_text_status: public
publication: The Journal of Experimental Medicine
volume: 211
number: 6
pagerange: 1167-1183
event_location: United States
issn: 1540-9538
citation:        Raimondi, C;    Fantin, A;    Lampropoulou, A;    Denti, L;    Chikh, A;    Ruhrberg, C;      (2014)    Imatinib inhibits VEGF-independent angiogenesis by targeting neuropilin 1-dependent ABL1 activation in endothelial cells.                   The Journal of Experimental Medicine , 211  (6)   pp. 1167-1183.    10.1084/jem.20132330 <https://doi.org/10.1084/jem.20132330>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/1431161/1/Imatinib%20inhibits%20VEGF-independent%20angiogenesis%20by%20targeting%20neuropilin%201%E2%80%93dependent%20ABL1%20activation%20in%20endothelial%20cells.pdf