RTVP-1 regulates glioma cell migration and invasion via interaction with N-WASP and hnRNPK
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Amotz Ziv-Av1, Nissim David Giladi1, Hae Kyung Lee2, Simona Cazacu2, Susan Finniss2, Cunli Xiang2, Maor H. Pauker1, Mira Barda-Saad1, Laila Poisson3 and Chaya Brodie1,2
1 Everard and Mina Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel
2 Davidson Laboratory of Cell Signaling and Tumorigenesis, Hermelin Brain Tumor Center, Department of Neurosurgery, MI, USA
3 Department of Public Health Sciences, Henry Ford Hospital, Detroit, MI, USA
Chaya Brodie, email:
Keywords: Glioblastoma, N-WASP, hnRNPK, Glioma cell migration
Received: April 02, 2015 Accepted: May 22, 2015 Published: June 15, 2015
Glioblastoma (GBM) are characterized by increased invasion into the surrounding normal brain tissue. RTVP-1 is highly expressed in GBM and regulates the migration and invasion of glioma cells. To further study RTVP-1 effects we performed a pull-down assay using His-tagged RTVP-1 followed by mass spectrometry and found that RTVP-1 was associated with the actin polymerization regulator, N-WASP. This association was further validated by co-immunoprecipitation and FRET analysis. We found that RTVP-1 increased cell spreading, migration and invasion and these effects were at least partly mediated by N-WASP. Another protein which was found by the pull-down assay to interact with RTVP-1 is hnRNPK. This protein has been recently reported to associate with and to inhibit the effect of N-WASP on cell spreading. hnRNPK decreased cell migration, spreading and invasion in glioma cells. Using co-immunoprecipitation we validated the interactions of hnRNPK with N-WASP and RTVP-1 in glioma cells. In addition, we found that overexpression of RTVP-1 decreased the association of N-WASP and hnRNPK. In summary, we report that RTVP-1 regulates glioma cell spreading, migration and invasion and that these effects are mediated via interaction with N-WASP and by interfering with the inhibitory effect of hnRNPK on the function of this protein.
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