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RTVP-1 regulates glioma cell migration and invasion via interaction with N-WASP and hnRNPK

  • Amotz Ziv-Av
  • , Nissim David Giladi
  • , Hae Kyung Lee
  • , Simona Cazacu
  • , Susan Finniss
  • , Cunli Xiang
  • , Maor H. Pauker
  • , Mira Barda-Saad
  • , Laila Poisson
  • , Chaya Brodie
  • Bar-Ilan University
  • Hermelin Brain Tumor Center
  • Henry Ford Health System

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)19826-19840
Number of pages15
JournalOncotarget
Volume6
Issue number23
DOIs
StatePublished - 14 Aug 2015

Funding

FundersFunder number
National Institutes of HealthR01-NS066303
National Institute of Neurological Disorders and StrokeR01NS066303

    Keywords

    • Glioblastoma
    • Glioma cell migration
    • N-WASP
    • hnRNPK

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