Abstract LB-101: Y-box binding protein-1 (YB-1) inhibition triggers differentiation of normal and cancer stem cells from the brain Conference Paper uri icon

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abstract

  • Abstract The Y-box-binding protein-1 (YB-1) is up-regulated in many human malignancies including glioblastoma (GBM). It is also essential for normal brain development, suggesting that YB-1 is part of a neural stem cell (NSC) network. Here we show that YB-1 was highly expressed in the subventricular zone (SVZ) of mouse fetal brain tissues but not in terminally differentiated primary astrocytes. Conversely, YB-1 knock-out mice had reduced Sox-2, nestin and musashi expression in the SVZ. While primary murine neurospheres were rich in YB-1, its expression was lost during glial differentiation. Likewise, YB-1, Sox-2, mushashi, Bmi-1 and nestin are coordinately expressed in SF188 cells and 9/9 GBM patient-derived primary CSCs. Silencing YB-1 with small interfering RNA attenuated the expression of these NSC markers, reduced neurosphere growth and triggered differentiation via coordinate loss of GSK3-β. Further, differentiation of CSCs with 1% serum or bone morphogenetic protein-4 (BMP-4) suppressed YB-1 protein expression. Likewise, YB-1 expression was lost during differentiation of normal human NSCs. Consistent with these observations, YB-1 was preferentially expressed in highly undifferentiated primary gliomas based on the analysis of WHO grade 1-IV tumors (n=49 cases). YB-1 was also co-expressed with Bmi-1 (Spearmans 0.80, p>0.001) and Sox-2 (Spearmans 0.66, p>0.001) based on the analysis of 282 cases of high-grade gliomas. These CSC markers were also highly expressed in 10/15 (67%) of GBM patients that subsequently relapsed. In conclusion, YB-1 is a key feature of stem cells where it functions to suppress differentiation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-101. doi:10.1158/1538-7445.AM2011-LB-101

authors

  • Fotovati, Abbas
  • Abu-Ali, Sam
  • Wang, Pei-Shan
  • Deleyrolle, Loic
  • Lee, Cathy
  • Tricott, Joanna
  • Chen, James
  • Franciosi, Sonia
  • Nakamura, Yas
  • Sugita, Yasuo
  • Uchiumi, Takeshi
  • Kuwano, Michihiko
  • Leavitt, Blair R
  • Singh, Sheila
  • Jury, Alexa
  • Jones, Chris
  • Wakimoto, Hiroaki
  • Reynolds, Brent A
  • Pallen, Catherine J
  • Dunn, Sandra E

publication date

  • April 15, 2011