Imatinib inhibits VEGF-independent angiogenesis by targeting neuropilin 1–dependent ABL1 activation in endothelial cells

Raimondi, Claudio; Fantin, Alessandro; Lampropoulou, Anastasia; Denti, Laura; Chikh, Anissa; Ruhrberg, Christiana

doi:10.1084/jem.20132330

Cited by 120 publications

(148 citation statements)

References 70 publications

(119 reference statements)

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“…Vegfa/Vegfa mutants lacked OFT defects, an attractive possibility is a role for NRP1 in conveying signals provided by extracellular matrix molecules such as fibronectin, which can induce EC motility and cytoskeletal remodeling in an NRP1-dependent, but SEMA3-and VEGF-A-independent, pathway via the ABL1 and ABL2 kinases (63). In support of this idea, fibronectin is abundant in the remodeling OFT (64) and integrins have been implicated in OFT remodeling (26,65).…”

Section: Sema/semamentioning

confidence: 98%

Neural crest–derived SEMA3C activates endothelial NRP1 for cardiac outflow tract septation

Plein¹,

Calmont²,

Fantin³

et al. 2015

J. Clin. Invest.

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Section: Sema/semamentioning

confidence: 98%

Neural crest–derived SEMA3C activates endothelial NRP1 for cardiac outflow tract septation

Plein¹,

Calmont²,

Fantin³

et al. 2015

J. Clin. Invest.

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“…Interestingly, expression of exogenous Tie2 only partially rescued Angpt1-mediated survival, suggesting that the Abl kinases modulate Angpt1-Tie2 signaling through additional mechanisms that go further that regulating Tie2 levels. ABL1 may also promote vascular development through neuropilin-1, a receptor for VEGFA (Raimondi, 2014;Raimondi et al, 2014). Endothelial deletion of Abl1 in Abl2-null mice resulted in focal loss of vasculature due to apoptosis, leading to localized tissue necrosis, with late-stage embryonic and perinatal lethality .…”

Section: Abl-dependent Regulation Of Cell Proliferation and Survival mentioning

confidence: 99%

Multifunctional Abl kinases in health and disease

Khatri

Wang

Pendergast

2016

Journal of Cell Science

117

145

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The Abelson tyrosine kinases were initially identified as drivers of leukemia in mice and humans. The Abl family kinases Abl1 and Abl2 regulate diverse cellular processes during development and normal homeostasis, and their functions are subverted during inflammation, cancer and other pathologies. Abl kinases can be activated by multiple stimuli leading to cytoskeletal reorganization required for cell morphogenesis, motility, adhesion and polarity. Depending on the cellular context, Abl kinases regulate cell survival and proliferation. Emerging data support important roles for Abl kinases in pathologies linked to inflammation. Among these are neurodegenerative diseases and inflammatory pathologies. Unexpectedly, Abl kinases have also been identified as important players in mammalian host cells during microbial pathogenesis. Thus, the use of Abl kinase inhibitors might prove to be effective in the treatment of pathologies beyond leukemia and solid tumors. In this Cell Science at a Glance article and in the accompanying poster, we highlight the emerging roles of Abl kinases in the regulation of cellular processes in normal cells and diverse pathologies ranging from cancer to microbial pathogenesis.

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“…Nrp and integrin coupling have been associated with pancreatic cancer cell invasion (89), increased fibronectin fibril assembly (90), breast cancer adhesion to laminin (91), breast cancer initiation (92), cancer cell extravasation and metastasis (81), breast cancer growth (93), and stem cell fate determination (94). Current data indicate that integrin engagement by Nrp may be independent, cooperative, or competitive with VEGFR engagement and signaling (95,96). The nature and role of integrin coupling to Nrp are an active area of research.…”

Section: Multi-faceted Biological Function Of Nrpmentioning

confidence: 99%

Neuropilin Functions as an Essential Cell Surface Receptor

Guo

Kooi

2015

Journal of Biological Chemistry

177

154

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The Neuropilins (Nrps) are a family of essential cell surface receptors involved in multiple fundamental cellular signaling cascades. Nrp family members have key functions in VEGF-dependent angiogenesis and semaphorin-dependent axon guidance, controlling signaling and cross-talk between these fundamental physiological processes. More recently, Nrp function has been found in diverse signaling and adhesive functions, emphasizing their role as pleiotropic co-receptors. Pathological Nrp function has been shown to be important in aberrant activation of both canonical and alternative pathways. Here we review key recent insights into Nrp function in human health and disease.The Nrps 2 are essential cell surface receptors with pleiotropic function in human health, functioning in many key biological processes including in the cardiovascular, neuronal, and immune systems (1). The two Nrp family members, Nrp1 and Nrp2, are type I transmembrane proteins that are conserved in all vertebrates and are ϳ40% identical at the amino acid level with a conserved domain structure. The Nrp extracellular region possesses five structured domains that are essential for ligand binding, a single transmembrane domain, and a short intracellular domain that possesses a PSD-95/Dlg/ZO-1 (PDZ)-binding motif (1).

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Imatinib inhibits VEGF-independent angiogenesis by targeting neuropilin 1–dependent ABL1 activation in endothelial cells

Abstract: Neuropilin 1 regulates angiogenesis in a VEGF-independent manner via association with ABL1, suggesting that Imatinib represents a novel opportunity for anti-angiogenic therapy.

Cited by 120 publications

References 70 publications

Neural crest–derived SEMA3C activates endothelial NRP1 for cardiac outflow tract septation

Neural crest–derived SEMA3C activates endothelial NRP1 for cardiac outflow tract septation

Multifunctional Abl kinases in health and disease

Neuropilin Functions as an Essential Cell Surface Receptor

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