Chondroitin sulphate‐modified neuropilin 1 is expressed in human tumour cells and modulates 3D invasion in the U87MG human glioblastoma cell line through a p130Cas‐mediated pathway
| Autor: | Ian Zachary, Pauliina Lehtolainen, Paul Frankel, Giovanna M. D'Abaco, Lili Cheng, Caroline Pellet-Many, Michelle Tickner |
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| Rok vydání: | 2008 |
| Předmět: |
Swine
Molecular Sequence Data Scientific Report Biology Biochemistry Mice chemistry.chemical_compound Cell Line Tumor Neuropilin 1 Genetics Animals Humans Gene silencing Neoplasm Invasiveness Amino Acid Sequence Molecular Biology Chondroitin Sulfates Mesenchymal stem cell Tyrosine phosphorylation Molecular biology Neuropilin-1 Hedgehog signaling pathway Rats Cell biology Vascular endothelial growth factor Crk-Associated Substrate Protein chemistry Cell culture RNA Interference Signal transduction Glioblastoma Signal Transduction |
| Zdroj: | EMBO reports. 9:983-989 |
| ISSN: | 1469-3178 1469-221X |
| DOI: | 10.1038/embor.2008.151 |
| Popis: | Neuropilin 1 (NRP1), a non-tyrosine kinase receptor for vascular endothelial growth factor and class 3 Semaphorins, is highly expressed in many human tumour cell lines, but its function is poorly understood. Here, we describe the expression of a new chondroitin sulphate-modified NRP1 (NRP1-CS) in human tumour cell lines. Expression of a non-modifiable NRP1 mutant (S612A) in U87MG human glioma cells results in enhanced invasion in three dimensions (3D), whereas wild-type NRP1 has no effect. Furthermore, the S612A NRP1 cells show a significant increase in p130Cas tyrosine phosphorylation compared with control and wild-type NRP1 cells. Silencing of p130Cas in S612A NRP1 cells resulted in a loss of increased invasive phenotype. Interestingly, p130Cas silencing does not inhibit basal 3D invasion, but leads to a mesenchymal to amoeboid transition. Biopsies from both low- and high-grade human gliomas show strong expression of NRP1, and little expression of NRP1-CS. Our data establish distinct roles for NRP1 and NRP1-CS in modulating a new NRP1-p130Cas signalling pathway contributing to glioblastoma cell invasion in 3D. |
| Databáze: | OpenAIRE |
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