PMID:21730024

Citation	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 and Dunn, SE (2011) YB-1 bridges neural stem cells and brain tumor-initiating cells via its roles in differentiation and cell growth. Cancer Res. 71:5569-78
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.
Links	PubMed Online version:10.1158/0008-5472.CAN-10-2805
Keywords	Animals; Base Sequence; Brain Neoplasms/pathology; Cell Differentiation/physiology; Cell Division/physiology; Cell Line, Tumor; Glioblastoma/pathology; Immunohistochemistry; Mice; Mice, Knockout; Neural Stem Cells/cytology; RNA, Small Interfering; Transcription Factors/physiology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:YBOX1		GO:0030308: negative regulation of cell growth	ECO:0000314:		P		Figure 2 shows "downregulation of YB-1 upon glial differentiation."	complete CACAO 5881

References

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