The novel Src kinase inhibitor M475271 inhibits VEGF-induced vascular endothelial-cadherin and beta-catenin phosphorylation but increases their association.

@article{Ali2006TheNS,
  title={The novel Src kinase inhibitor M475271 inhibits VEGF-induced vascular endothelial-cadherin and beta-catenin phosphorylation but increases their association.},
  author={Nermin Ali and Masanori Yoshizumi and Seiji Yano and Saburo Sone and Hideki Ohnishi and Keisuke Ishizawa and Yasuhisa Kanematsu and Koichiro Tsuchiya and Toshiaki Tamaki},
  journal={Journal of pharmacological sciences},
  year={2006},
  volume={102 1},
  pages={
          112-20
        }
}
M475271, 4-quinazolinamine, N-(2-chloro-5-methoxyphenyl)-6-methoxy-7-[(1-methyl-4-piperidinyl) methoxy]-(9Cl), is a new anilinoquinazoline derivative that displays selective inhibition of Src kinase activity and tumor growth in vivo. Vascular endothelial growth factor (VEGF)-induced angiogenesis plays a pivotal role in tumor growth and metastasis. Vascular endothelial (VE)-cadherin is an endothelial cell-specific adhesion molecule that can interact with the cytoskeleton via several anchoring… 
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References

SHOWING 1-10 OF 37 REFERENCES

A novel Src kinase inhibitor, M475271, inhibits VEGF-induced human umbilical vein endothelial cell proliferation and migration.

The findings suggest that M475271 attenuates VEGF-induced HUVEC proliferation and migration through the inhibition of signaling pathways involving Src, ERK1/2, and/or p38.

Inhibition of vascular endothelial growth factor-induced angiogenesis by resveratrol through interruption of Src-dependent vascular endothelial cadherin tyrosine phosphorylation.

The data suggest that resveratrol inhibition of VEGF-induced angiogenesis was mediated by disruption of ROS-dependent Src kinase activation and the subsequent VE-cadherin tyrosine phosphorylation.

Vascular endothelial growth factor induces VE-cadherin tyrosine phosphorylation in endothelial cells.

It is suggested that tyrosine phosphorylation of its components may be involved in the the loosening of cell-cell contacts in established vessels to modulate transendothelial permeability and to allow sprouting and cell migration during angiogenesis.

Src mediates stimulation by vascular endothelial growth factor of the phosphorylation of focal adhesion kinase at tyrosine 861, and migration and anti-apoptosis in endothelial cells.

Src-dependent FAK phosphorylation at Y861 is identified as a novel VEGF-induced signalling pathway in endothelial cells and suggested that this pathway might be involved in the mechanisms mediating VEGf-induced endothelial cell migration and anti-apoptosis.

Topotecan inhibits VEGF‐ and bFGF‐induced vascular endothelial cell migration via downregulation of the PI3K‐Akt signaling pathway

Results suggest that the antiangiogenic activity of topotecan is mediated in part by downregulating the PI3K‐Akt signaling pathway.

Src family kinase inhibitor PP2 restores the E-cadherin/catenin cell adhesion system in human cancer cells and reduces cancer metastasis.

The data demonstrate that PP2 can activate the functioning of the E-cadherin-mediated cell adhesion system, which is associated with the suppression of metastasis in cancer cells, and selective inhibition of Src activation may be potentially useful in the prevention of cancer metastasis.

Differential regulation of sphingosine-1-phosphate- and VEGF-induced endothelial cell chemotaxis. Involvement of G(ialpha2)-linked Rho kinase activity.

S1P is confirmed as a potent endothelial cell chemoattractant through G(1alpha2)-coupled Edg receptors linked to Rho-associated kinase and p38 MAP kinase activation and the divergence in signaling pathways evoked by S1P and VEGF suggests complex and agonist-specific regulation of endothelialcell angiogenic responses.

Dynamics of vascular endothelial-cadherin and beta-catenin localization by vascular endothelial growth factor-induced angiogenesis in human umbilical vein cells.

By metabolic labeling of HUVECs it was found that de novo synthesis of VE-cadherin was not essential for the formation of new adherens junctions, indicating that they are only weakly associated with the actin-based cytoskeleton.

E-Cadherin Suppresses Cellular Transformation by Inhibiting β-Catenin Signaling in an Adhesion-Independent Manner

E-cadherin–mediated growth suppression was not accompanied by overall depletion of β-catenin from the cytosol and nucleus, which suggests that there are mechanisms to regulate β- catenin signaling in addition to controlling its level of accumulation.

Selective requirement for Src kinases during VEGF-induced angiogenesis and vascular permeability.