Expression of the neural RNA‐binding protein Musashi1 in human gliomas

Toda, Masahiro; Iizuka, Yukihiko; Yu, Wangjie; Imai, Toshio; Ikeda, Eiji; Yoshida, Kazunari; Kawase, Takeshi; Kawakami, Yutaka; Uyemura, Keiichi

doi:10.1002/glia.1034

Cited by 158 publications

(143 citation statements)

References 34 publications

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“…32) Musashi 1 containing two ribonucleoprotein (RNP)-type RNA-binding domains (RBDs) is also overexpressed in malignant gliomas. 40) These results suggest that various types of RNA-binding proteins are involved in cell proliferation, and expression alterations of those RNA-binding proteins often cause tumor formation. This prompted us to examine the expression of Hqk in human tumors.…”

Section: Discussionmentioning

confidence: 92%

Expression of Hqk Encoding a KH RNA Binding Protein Is Altered in Human Glioma

Kondo

Murata

et al. 2002

Japanese Journal of Cancer Research

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Section: Discussionmentioning

confidence: 92%

Expression of Hqk Encoding a KH RNA Binding Protein Is Altered in Human Glioma

Kondo

Murata

et al. 2002

Japanese Journal of Cancer Research

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“…26 Here we describe an elevated ENPP1 expression in GSCs compared with normal brain extracts and fNSCs. E-NPP1-deficient GSCs are characterised by downregulation of known stem cell markers, such as CD133, LHX2, MSI1, LGR5 and CD15, 4,8,9,34,35 as well as an overall downregulation of stem cell-associated genes as seen by comparison with published stem cell gene signatures. 24,25 Moreover, GFAP and S100 beta, differentiation marker delineating the astrocytic cell lineage, are upregulated upon knockdown of ENPP1 in cultured GSCs.…”

Section: Discussionmentioning

confidence: 99%

“…Glioblastoma stem-like cells (GSCs) share properties with neural precursor cells, such as a capacity for self-renewal, differentiation and maintained proliferation, as well as stem cell marker expression. 4,5,8,9 GSCs were originally defined by expression of CD133 (Prominin-1) and its extracellular AC133 epitope. 4 Although recent studies have shown that GSCs are not entirely restricted to the CD133-positive cell population, 10,11 there is a large body of evidence linking enhanced CD133 expression to poor prognosis in glioblastoma.…”

mentioning

confidence: 99%

Stem cell characteristics in glioblastoma are maintained by the ecto-nucleotidase E-NPP1

et al. 2014

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Glioblastomas are highly aggressive brain tumours and are characterised by substantial cellular heterogeneity within a single tumour. A sub-population of glioblastoma stem-like cells (GSCs) that shares properties with neural precursor cells has been described, exhibiting resistance to therapy and therefore being considered responsible for the high recurrence rate in glioblastoma. To elucidate the underlying cellular processes we investigated the role of phosphatases in the GSC phenotype, using an in vitro phosphatome-wide RNA interference screen. We identified a set of genes, the knockdown of which induces a significant decrease in the glioma stem cell marker CD133, indicating a role in the glioblastoma stem-like phenotype. Among these genes, the ecto-nucleotidase ENPP1 (ectonucleotide pyrophosphatase/phosphodiesterase 1) was found to be highly expressed in GSCs compared with normal brain and neural stem cells. Knockdown of ENPP1 in cultured GSCs resulted in an overall downregulation of stem cell-associated genes, induction of differentiation into astrocytic cell lineage, impairment of sphere formation, in addition to increased cell death, accumulation of cells in G1/G0 cell cycle phase and sensitisation to chemotherapeutic treatment. Genome-wide gene expression analysis and nucleoside and nucleotide profiling revealed that knockdown of ENPP1 affects purine and pyrimidine metabolism, suggesting a link between ENPP1 expression and a balanced nucleoside-nucleotide pool in GSCs. The phenotypic changes in E-NPP1-deficient GSCs are assumed to be a consequence of decreased transcriptional function of E2F1. Together, these results reveal that E-NPP1, by acting upstream of E2F1, is indispensable for the maintenance of GSCs in vitro and hence required to keep GSCs in an undifferentiated, proliferative state. Glioblastoma, classified by the WHO (World Health Organization) as grade IV astrocytoma, 1 is the most common primary malignant brain tumour in adults. Despite progress in surgical resection, radiation and chemotherapy, glioblastoma remains a deadly disease with a median survival time of about 1 year. 2 One particular therapeutic challenge for glioblastoma treatment is posed by their remarkable intratumoural cellular heterogeneity. Several studies indicate the existence of a highly tumourigenic, sub-population of cancer cells with stemlike characteristics. [3][4][5] There is substantial evidence that these so-called cancer stem cells have inherent chemotherapy and radiation resistance. 6,7 These findings suggest that cancer cells harbouring stem cell-like characteristics are responsible for ineffective therapy, explaining high recurrence rates despite significant reduction in tumour volume. Glioblastoma stem-like cells (GSCs) share properties with neural precursor cells, such as a capacity for self-renewal, differentiation and maintained proliferation, as well as stem cell marker expression. 4,5,8,9 GSCs were originally defined by expression of CD133 (Prominin-1) and its extracellular AC133 epitope. 4 Although recent...

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“…The role of neural stem cells and multipotential progenitors as cell-of-origin of glioblastoma has been suggested by the detection of positive immunoreactivity for immature markers such as nestin in human tumors (Dahlstrand et al, 1992;Toda et al, 2001;Ignatova et al, 2002;Bouvier et al, 2003) and by studies in transgenic mice overexpressing activated Ras and Akt in nestin ϩ cells (Holland, 2000). et al, 2004), its mutation is observed in sphere-forming cells isolated from human glioblastoma (Ignatova et al, 2002) and its expression in the adult brain is confined to germinal areas (van Lookeren Campagne and Gill, 1998), we postulated that characterization of the changes induced by loss of p53 in cells of the adult SVZ could lead us to a better understanding of the genesis of glial tumors.…”

Section: Discussionmentioning

confidence: 99%

Loss ofp53Induces Changes in the Behavior of Subventricular Zone Cells: Implication for the Genesis of Glial Tumors

Gil-Perotín¹,

Marin-Husstege²,

Li³

et al. 2006

J. Neurosci.

196

182

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The role of multipotential progenitors and neural stem cells in the adult subventricular zone (SVZ) as cell-of-origin of glioblastoma has been suggested by studies on human tumors and transgenic mice. However, it is still unknown whether glial tumors are generated by all of the heterogeneous SVZ cell types or only by specific subpopulations of cells. It has been proposed that transformation could result from lack of apoptosis and increased self-renewal, but the definition of the properties leading to neoplastic transformation of SVZ cells are still elusive. This studyaddressesthesequestionsinmicecarryingthedeletionofp53,atumor-suppressorgeneexpressedintheSVZ.Weshowherethat,although loss of p53 by itself is not sufficient for tumor formation, it provides a proliferative advantage to the slow-and fast-proliferating subventricular zone (SVZ) populations associated with their rapid differentiation. This results in areas of increased cell density that are distributed along the walls of the lateral ventricles and often associated with increased p53-independent apoptosis. Transformation occurs when loss of p53 is associated with a mutagenic stimulus and is characterized by dramatic changes in the properties of the quiescent adult SVZ cells, including enhanced self-renewal, recruitment to the fast-proliferating compartment, and impaired differentiation.Together, these findings provide a cellular mechanism for how the slow-proliferating SVZ cells can give rise to glial tumors in the adult brain.

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Expression of the neural RNA‐binding protein Musashi1 in human gliomas

Cited by 158 publications

References 34 publications

Expression of Hqk Encoding a KH RNA Binding Protein Is Altered in Human Glioma

Expression of Hqk Encoding a KH RNA Binding Protein Is Altered in Human Glioma

Stem cell characteristics in glioblastoma are maintained by the ecto-nucleotidase E-NPP1

Loss ofp53Induces Changes in the Behavior of Subventricular Zone Cells: Implication for the Genesis of Glial Tumors

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