Critical Role of S1PR1 and Integrin β4 in HGF/c-Met-mediated Increases in Vascular Integrity

Ephstein, Y.; Singleton, Patrick A.; Chen, Weiguo; Wang, Lichun; Salgia, Ravi; Kanteti, Prasad; Dudek, Steven M.; Garcia, Joe G.N.; Jacobson, Jeffrey R.

doi:10.1074/jbc.m112.404780

Cited by 41 publications

(40 citation statements)

References 54 publications

(72 reference statements)

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“…Enhancement of lung colonization by bloodborne breast cancer cells in response to S1PR 1 antagonism may involve enhanced plasma protein egress into the lung that supports tumor cell extravasation and provides a favorable environment for tumor cell growth. In addition, the S1PR 1 may trigger changes in endothelial integrin expression that are involved in cancer cell arrest necessary for metastatic ingress into the target organ (14).…”

Section: Discussionmentioning

confidence: 99%

Host endothelial S1PR₁ regulation of vascular permeability modulates tumor growth

Sarkisyan

Nguyen

Felding

et al. 2014

American Journal of Physiology-Cell Physiology

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Understanding vascular growth and maturation in developing tumors has important implications for tumor progression, spread, and ultimately host survival. Modulating the signaling of endothelial G protein-coupled receptors (GPCRs) in blood and lymphatic vessels can enhance or limit tumor progression. Sphingosine 1-phosphate receptor 1 (S1PR1) is a GPCR for circulating lysophospholipid S1P that is highly expressed in blood and lymphatic vessels. Using the S1PR1- enhanced green fluorescent protein (eGFP) mouse model in combination with intravital imaging and pharmacologic modulation of S1PR1 signaling, we show that boundary conditions of high and low S1PR1 signaling retard tumor progression by enhancing or destabilizing neovasculature integrity, respectively. In contrast, midrange S1PR1 signaling, achieved by receptor antagonist titration, promotes abundant growth of small, organized vessels and thereby enhances tumor progression. Furthermore, in vivo S1PR1 antagonism supports lung colonization by circulating tumor cells. Regulation of endothelial S1PR1 dynamically controls vascular integrity and maturation and thus modulates angiogenesis, tumor growth, and hematogenous metastasis.

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Section: Discussionmentioning

confidence: 99%

Host endothelial S1PR₁ regulation of vascular permeability modulates tumor growth

Sarkisyan

Nguyen

Felding

et al. 2014

American Journal of Physiology-Cell Physiology

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“…, and Akt in Lung ECs-Binding of HGF to its receptor, c-Met, induces dimerization and autophosphorylation of specific tyrosine residues resulting in enhanced kinase activity and activation of diverse intracellular signaling pathways including MAPKs, STAT3, Rac1, and Akt (7, 10, 41-46), which promote EC barrier function (47,48). To further characterize HGF/cMet signaling axis in EC function, we used SU11274 (49) to inhibit HGF-mediated c-Met phosphorylation.…”

Section: Down-regulation Of C-met or Inhibition Of C-met Phosphorylatmentioning

confidence: 99%

Role of c-Met/Phosphatidylinositol 3-Kinase (PI3k)/Akt Signaling in Hepatocyte Growth Factor (HGF)-mediated Lamellipodia Formation, Reactive Oxygen Species (ROS) Generation, and Motility of Lung Endothelial Cells

Usatyuk

Mohan

et al. 2014

Journal of Biological Chemistry

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Background: Lamellipodia structures provide a platform for the spatio-temporal localization of key components necessary for cell migration. Results: HGF activates c-Met/PI3k/Akt signaling axis, which is essential for the recruitment of actin, cortactin, p47phox , and Rac1and ROS production in lamellipodia. Conclusion: HGF-induced spatio-temporal localization of cytoskeletal proteins and NADPH oxidase components regulate lamellipodial ROS and cell migration. Significance: This study identifies a novel role for lamellipodial ROS in cell motility.

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“…26 Of note, the receptors for S1P, G protein-coupled receptors, localize and activate in lipid rafts. 27 Whether targeted cholesterol efflux mediated by AIBP regulates the signals initiated from S1P is an intriguing question that merits further study.…”

Section: Hdl In the Regulation Of Angiogenesis And Lymphangiogenesismentioning

confidence: 99%

AIBP: A Novel Molecule at the Interface of Cholesterol Transport, Angiogenesis, and Atherosclerosis

Zhu¹,

Fang

2015

Methodist DeBakey Cardiovascular Journal

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Cardiovascular disease, which is often driven by hypercholesterolemia and subsequent coronary atherosclerosis, is the numberone cause of morbidity and mortality in the United States. Based on long-term epidemiological studies, high-density lipoprotein cholesterol (HDL-C) levels are inversely correlated with risk for coronary artery disease (CAD). HDL-mediated reverse cholesterol transport (RCT) is responsible for cholesterol removal from the peripheral tissues and return to the liver for final elimination. In atherosclerosis, intraplaque angiogenesis promotes plaque growth and increases plaque vulnerability. Conceivably, the acceleration of RCT and disruption of intraplaque angiogenesis would inhibit atherosclerosis and reduce CAD. We have identified a protein called apoA-I binding protein (AIBP) that augments HDL functionality by accelerating cholesterol efflux. Furthermore, AIBP inhibits vascular endothelial growth factor receptor 2 activation in endothelial cells and limits angiogenesis. 2 The following discusses the prospect of using AIBP as a novel therapeutic approach for the treatment of CAD.L. Zhu, B.S.L. Fang, Ph.D.

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Critical Role of S1PR1 and Integrin β4 in HGF/c-Met-mediated Increases in Vascular Integrity

Cited by 41 publications

References 54 publications

Host endothelial S1PR₁ regulation of vascular permeability modulates tumor growth

Host endothelial S1PR₁ regulation of vascular permeability modulates tumor growth

Role of c-Met/Phosphatidylinositol 3-Kinase (PI3k)/Akt Signaling in Hepatocyte Growth Factor (HGF)-mediated Lamellipodia Formation, Reactive Oxygen Species (ROS) Generation, and Motility of Lung Endothelial Cells

AIBP: A Novel Molecule at the Interface of Cholesterol Transport, Angiogenesis, and Atherosclerosis

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Critical Role of S1PR1 and Integrin β4 in HGF/c-Met-mediated Increases in Vascular Integrity

Cited by 41 publications

References 54 publications

Host endothelial S1PR1 regulation of vascular permeability modulates tumor growth

Host endothelial S1PR1 regulation of vascular permeability modulates tumor growth

Role of c-Met/Phosphatidylinositol 3-Kinase (PI3k)/Akt Signaling in Hepatocyte Growth Factor (HGF)-mediated Lamellipodia Formation, Reactive Oxygen Species (ROS) Generation, and Motility of Lung Endothelial Cells

AIBP: A Novel Molecule at the Interface of Cholesterol Transport, Angiogenesis, and Atherosclerosis

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Host endothelial S1PR₁ regulation of vascular permeability modulates tumor growth

Host endothelial S1PR₁ regulation of vascular permeability modulates tumor growth