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Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Cancer+Cell 2012 ; 22 (1): 21-35 Nephropedia Template TP
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VEGF Inhibits Tumor Cell Invasion and Mesenchymal Transition Through a MET/VEGFR2 Complex #MMPMID22789536
Lu KV; Chang JP; Parachoniak CA; Pandika MM; Aghi MK; Meyronet D; Isachenko N; Fouse SD; Phillips JJ; Cheresh DA; Park M; Bergers G
Cancer Cell 2012[Jul]; 22 (1): 21-35 PMID22789536show ga
Inhibition of VEGF signaling leads to a pro-invasive phenotype in mouse models of glioblastoma multiforme (GBM) and in a subset of GBM patients treated with bevacizumab. Here we demonstrate that vascular endothelial growth factor (VEGF) directly and negatively regulates tumor cell invasion through enhanced recruitment of the protein tyrosine phosphatase 1B (PTP1B) to a MET/VEGFR2 heterocomplex, thereby suppressing HGF-dependent MET phosphorylation and tumor cell migration. Consequently, VEGF blockade restores and increases MET activity in GBM cells in a hypoxia-independent manner, while inducing a program reminiscent of epithelial-to-mesenchymal transition highlighted by a T-cadherin to N-cadherin switch and enhanced mesenchymal features. Inhibition of MET in GBM mouse models blocks mesenchymal transition and invasion provoked by VEGF ablation, resulting in substantial survival benefit.