title: YB-1 bridges neural stem cells and brain tumor-initiating cells via its roles in differentiation and cell growth.
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.
authors: University of British Columbia, Vancouver, British Columbia, Canada.
authors: Abbas
authors: A
authors: Fotovati
authors: Samah
authors: S
authors: Abu-Ali
authors: Pei-Shan
authors: PS
authors: Wang
authors: Loic P
authors: LP
authors: Deleyrolle
authors: Cathy
authors: C
authors: Lee
authors: Joanna
authors: J
authors: Triscott
authors: James Y
authors: JY
authors: Chen
authors: Sonia
authors: S
authors: Franciosi
authors: Yasuhiro
authors: Y
authors: Nakamura
authors: Yasuo
authors: Y
authors: Sugita
authors: Takeshi
authors: T
authors: Uchiumi
authors: Michihiko
authors: M
authors: Kuwano
authors: Blair R
authors: BR
authors: Leavitt
authors: Sheila K
authors: SK
authors: Singh
authors: Alexa
authors: A
authors: Jury
authors: Chris
authors: C
authors: Jones
authors: Hiroaki
authors: H
authors: Wakimoto
authors: Brent A
authors: BA
authors: Reynolds
authors: Catherine J
authors: CJ
authors: Pallen
authors: Sandra E
authors: SE
authors: Dunn
mesh_terms: D000818:Animals; D001483:Base Sequence; D001932:Brain Neoplasms / Q000473:pathology*; D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division / Q000502:physiology*; D045744:Cell Line, Tumor; D005909:Glioblastoma / Q000473:pathology*; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D058953:Neural Stem Cells / Q000166:cytology*; D034741:RNA, Small Interfering; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D034741:RNA, Small Interfering; D014157:Transcription Factors; C541744:Ybx1 protein, mouse