YB-1 bridges neural stem cells and brain tumor-initiating cells via its roles in differentiation and cell growth

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

Research output: Contribution to journalArticle

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Abstract

The Y-box binding protein 1 (YB-1) is upregulated 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 knockout mice had reduced Sox-2, nestin, and musashi-1 expression in the SVZ. Although primary murine neurospheres were rich in YB-1, its expression was lost during glial differentiation. Glial tumors often express NSC markers and tend to loose the cellular control that governs differentiation; therefore, we addressed whether YB-1 served a similar role in cancer cells. YB-1, Sox-2, musashi-1, Bmi-1, and nestin are coordinately expressed in SF188 cells and 9/9 GBM patient-derived primary brain tumor-initiating cells (BTIC). Silencing YB-1 with siRNA attenuated the expression of these NSC markers, reduced neurosphere growth, and triggered differentiation via coordinate loss of GSK3-β. Furthermore, differentiation of BTIC with 1% serum or bone morphogenetic protein-4 suppressed YB-1 protein expression. Likewise, YB-1 expression was lost during differentiation of normal human NSCs. Consistent with these observations, YB-1 expression increased with tumor grade (n = 49 cases). YB-1 was also coexpressed 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 proteins were highly expressed in 10/15 (67%) of GBM patients that subsequently relapsed. In conclusion, YB-1 correlatively expresses with NSC markers where it functions to promote cell growth and inhibit differentiation.

Original languageEnglish
Pages (from-to)5569-5578
Number of pages10
JournalCancer Research
Volume71
Issue number16
DOIs
Publication statusPublished - Aug 15 2011

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Neural Stem Cells
Neoplastic Stem Cells
Brain Neoplasms
Cell Differentiation
Glioblastoma
Nestin
Lateral Ventricles
Growth
Neuroglia
Neoplasms
Y-Box-Binding Protein 1
Bone Morphogenetic Protein 4
Brain
Knockout Mice
Glioma
Astrocytes
Small Interfering RNA
Proteins
Fetus
Serum

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Fotovati, A., Abu-Ali, S., Wang, P. S., Deleyrolle, L. P., Lee, C., Triscott, J., ... Dunn, S. E. (2011). YB-1 bridges neural stem cells and brain tumor-initiating cells via its roles in differentiation and cell growth. Cancer Research, 71(16), 5569-5578. https://doi.org/10.1158/0008-5472.CAN-10-2805

YB-1 bridges neural stem cells and brain tumor-initiating cells via its roles in differentiation and cell growth. / Fotovati, Abbas; Abu-Ali, Samah; Wang, Pei Shan; Deleyrolle, Loic P.; Lee, Cathy; Triscott, Joanna; Chen, James Y.; Franciosi, Sonia; Nakamura, Yasuhiro; Sugita, Yasuo; Uchiumi, Takeshi; Kuwano, Michihiko; Leavitt, Blair R.; Singh, Sheila K.; Jury, Alexa; Jones, Chris; Wakimoto, Hiroaki; Reynolds, Brent A.; Pallen, Catherine J.; Dunn, Sandra E.

In: Cancer Research, Vol. 71, No. 16, 15.08.2011, p. 5569-5578.

Research output: Contribution to journalArticle

Fotovati, A, Abu-Ali, S, Wang, PS, Deleyrolle, LP, Lee, C, Triscott, J, Chen, JY, Franciosi, S, Nakamura, Y, Sugita, Y, Uchiumi, T, Kuwano, M, Leavitt, BR, Singh, SK, Jury, A, Jones, C, Wakimoto, H, Reynolds, BA, Pallen, CJ & Dunn, SE 2011, 'YB-1 bridges neural stem cells and brain tumor-initiating cells via its roles in differentiation and cell growth', Cancer Research, vol. 71, no. 16, pp. 5569-5578. https://doi.org/10.1158/0008-5472.CAN-10-2805
Fotovati, Abbas ; Abu-Ali, Samah ; Wang, Pei Shan ; Deleyrolle, Loic P. ; Lee, Cathy ; Triscott, Joanna ; Chen, James Y. ; Franciosi, Sonia ; Nakamura, Yasuhiro ; Sugita, Yasuo ; Uchiumi, Takeshi ; Kuwano, Michihiko ; Leavitt, Blair R. ; Singh, Sheila K. ; Jury, Alexa ; Jones, Chris ; Wakimoto, Hiroaki ; Reynolds, Brent A. ; Pallen, Catherine J. ; Dunn, Sandra E. / YB-1 bridges neural stem cells and brain tumor-initiating cells via its roles in differentiation and cell growth. In: Cancer Research. 2011 ; Vol. 71, No. 16. pp. 5569-5578.
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abstract = "The Y-box binding protein 1 (YB-1) is upregulated 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 knockout mice had reduced Sox-2, nestin, and musashi-1 expression in the SVZ. Although primary murine neurospheres were rich in YB-1, its expression was lost during glial differentiation. Glial tumors often express NSC markers and tend to loose the cellular control that governs differentiation; therefore, we addressed whether YB-1 served a similar role in cancer cells. YB-1, Sox-2, musashi-1, Bmi-1, and nestin are coordinately expressed in SF188 cells and 9/9 GBM patient-derived primary brain tumor-initiating cells (BTIC). Silencing YB-1 with siRNA attenuated the expression of these NSC markers, reduced neurosphere growth, and triggered differentiation via coordinate loss of GSK3-β. Furthermore, differentiation of BTIC with 1{\%} serum or bone morphogenetic protein-4 suppressed YB-1 protein expression. Likewise, YB-1 expression was lost during differentiation of normal human NSCs. Consistent with these observations, YB-1 expression increased with tumor grade (n = 49 cases). YB-1 was also coexpressed 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 proteins were highly expressed in 10/15 (67{\%}) of GBM patients that subsequently relapsed. In conclusion, YB-1 correlatively expresses with NSC markers where it functions to promote cell growth and inhibit differentiation.",
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AU - Lee, Cathy

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AU - Chen, James Y.

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AU - Leavitt, Blair R.

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