alexa RTVP-1 Promotes The Mesenchymal Transformation Of Glioma Stem Cells Via The CXCR4 And The IL-6 Pathways
ISSN: 1948-5956

Journal of Cancer Science & Therapy
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4th World Congress on Cancer Science & Therapy
October 20-22, 2014 DoubleTree by Hilton Hotel Chicago-North Shore Conference Center, USA

Chaya Brodie, Hae Kyung Lee, Nis David Giladi, Susan Finniss, Simona Cazacu, Cunli Xiang, Laila Poisson and Amotz Ziv-Av
Accepted Abstracts: J Cancer Sci Ther
DOI: 10.4172/1948-5956.S1.035
Abstract
Glioblastoma, the most aggressive primary brain tumors, are categorized into the major subgroups: Proneural, neural, classical and mesenchymal, the latter being characterized by increased invasion and poor prognosis. We recently identified RTVP-1 as a glioma-associated protein that regulates glioma cell migration and invasion. Using ChiP analyses, we found that the RTVP-1 promoter bind STAT3 and C/EBPbeta. Analysis of TCGA tumor specimens demonstrated that the expression of RTVP-1 was higher in the mesenchymal GBM and was inversely correlated with patient survival. We further found that RTVP-1 was expressed in glioma stem cells (GSCs) but not in human neural stem cells (NSCs). Overexpression of RTVP-1 in NSCs induced their mesenchymal transformation, whereas silencing of RTVP-1 in GSCs decreased their mesenchymal signature, increased their neural phenotypes and inhibited their self renewal and stemness. Silencing of RTVP-1 also decreased tumor volume of GSC-derived xenografts and increased animal survival. Using gene array analysis of RTVP-1 silenced cells we identified IL-6 and CXCR4 as major mediators of RTVP-1 effects on the mesenchymal transformation and self-renewal of GSCs. Using a pull down assay with His-tagged RTVP-1 and FRET analysis, we identified HSP27, N-WASP and hnRNPK as novel interacting proteins of RTVP-1, that mediate its effects on GSC migration and invadopodia formation. In summary, RTVP-1 promotes the mesenchymal transformation of GSCs and induces self-renewal and migration by the increased expression of IL-6 and CXCR4 and via its interaction with N-WASP, hnRNPK and HSP27. Collectively, these results implicate RTVP-1 as a novel prognostic marker and therapeutic target in GBM.
Biography
Chaya Brodie has completed her PhD at Bar-Ilan University, Israel and postdoctoral studies at University of Colorado and National Jewish Center for Immunology and Respiratory Medicine. She is a Senior Staff Scientist and the Director of Translational Science in the Hermelin Brain Tumor Center, Henry Ford Hospital, Detroi, MI and a Professor in the Faculty of Life Sciences, Bar-Ilan University, Israel. She has published more than 135 papers in reputed journals and has served as a reviewer in various NIH study sections and in international foundations and societies.
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