Brain tumour stem cells: the undercurrents of human brain cancer and their relationship to neural stem cells

Dirks, Peter B.

doi:10.1098/rstb.2006.2017

Cited by 65 publications

(51 citation statements)

References 165 publications

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“…A ccording to the cancer stem cell (CSC) hypothesis, tumors are formed and maintained by a population of undifferentiated cells that are characterized by their ability for self-renewal and to induce tumorigenesis (1,2). Critical to CSC research is their prospective identification and isolation from tumor tissue.…”

mentioning

confidence: 99%

Activation of PI3K/Akt pathway by CD133-p85 interaction promotes tumorigenic capacity of glioma stem cells

Wei

Jiang

Zou

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

241

225

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The biological significance of a known normal and cancer stem cell marker CD133 remains elusive. We now demonstrate that the phosphorylation of tyrosine-828 residue in CD133 C-terminal cytoplasmic domain mediates direct interaction between CD133 and phosphoinositide 3-kinase (PI3K) 85 kDa regulatory subunit (p85), resulting in preferential activation of PI3K/protein kinase B (Akt) pathway in glioma stem cell (GSC) relative to matched nonstem cell. CD133 knockdown potently inhibits the activity of PI3K/Akt pathway with an accompanying reduction in the self-renewal and tumorigenicity of GSC. The inhibitory effects of CD133 knockdown could be completely rescued by expression of WT CD133, but not its p85-binding deficient Y828F mutant. Analysis of glioma samples reveals that CD133 Y828 phosphorylation level is correlated with histopathological grade and overlaps with Akt activation. Our results identify the CD133/PI3K/Akt signaling axis, exploring the fundamental role of CD133 in glioma stem cell behavior.

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mentioning

confidence: 99%

Activation of PI3K/Akt pathway by CD133-p85 interaction promotes tumorigenic capacity of glioma stem cells

Wei

Jiang

Zou

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

241

225

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“…Studies of these cells have revealed that they share certain features with neural stem cells (NSCs), leading to the enticing hypothesis that tumour-initiating cells in the brain arise from the oncogenic transformation of endogenous NSCs, or from dedifferentiated committed neural progenitors or mature glial cells (Dirks, 2008). If such BTSCs can be identified, they can be specifically targeted in the treatment of brain tumours, an exciting possibility with obvious clinical impact.…”

Section: Introductionmentioning

confidence: 99%

“…In recent years, tumour cells with stem-like properties, called brain tumour stem cells (BTSCs), have been isolated from various adult and pediatric brain tumours, leading to the suggestion that cancer growth might be fuelled by a small population of such cells (Dirks, 2008). Studies of these cells have revealed that they share certain features with neural stem cells (NSCs), leading to the enticing hypothesis that tumour-initiating cells in the brain arise from the oncogenic transformation of endogenous NSCs, or from dedifferentiated committed neural progenitors or mature glial cells (Dirks, 2008).…”

Section: Introductionmentioning

confidence: 99%

A cross-disciplinary approach to understanding neural stem cells in development and disease

Henrique

Bally‐Cuif

2010

Development

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The Company of Biologists recently launched a new series of workshops aimed at bringing together scientists with different backgrounds to discuss cutting edge research in emerging and cross-disciplinary areas of biology. The first workshop was held at Wilton Park, Sussex, UK, and the chosen theme was 'Neural Stem Cells in Development and Disease', which is indeed a hot topic, not only because of the potential use of neural stem cells in cell replacement therapies to treat neurodegenerative diseases, but also because alterations in their behaviour can, in certain cases, lie at the origin of brain tumours and other diseases.

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“…5 The other factors that contribute to resistance in GBM include (a) high degree of heterogeneity of the tumor and (b) the microenvironment comprising of tumor-associated parenchymal cells such as vascular cells, microglia, and peripheral immune cells, and (c) cancer stem cells (CSC) that actively promote tumor progression. 6 The CSC or glioma initiating cells/glioma stem cells (GIC/GSC) constitute a small population of a tumor, retain stem-like cell features including self-renewal capacity that is crucial for tumorigenicity, 7,8 and confer resistance to radiotherapy and chemotherapy, which leads to recurrence and cancer relapse. [9][10][11] Therefore, GSCs represent a promising target for anti-GBM therapies.…”

Section: Introductionmentioning

confidence: 99%

Mammalian target of rapamycin inhibitors, temsirolimus and torin 1, attenuate stemness-associated properties and expression of mesenchymal markers promoted by phorbol-myristate-acetate and oncostatin-M in glioblastoma cells

et al. 2017

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The phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin signaling pathway is crucial for tumor survival, proliferation, and progression, making it an attractive target for therapeutic intervention. In glioblastoma, activated mammalian target of rapamycin promotes invasive phenotype and correlates with poor patient survival. A wide range of mammalian target of rapamycin inhibitors are currently being evaluated for cytotoxicity and anti-proliferative activity in various tumor types but are not explored sufficiently for controlling tumor invasion and recurrence. We recently reported that mammalian target of rapamycin inhibitors-rapamycin, temsirolimus, torin 1, and PP242-suppressed invasion and migration promoted by tumor necrosis factor-alpha and phorbol-myristate-acetate in glioblastoma cells. As aggressive invasion and migration of tumors are associated with mesenchymal and stem-like cell properties, this study aimed to examine the effect of mammalian target of rapamycin inhibitors on these features in glioblastoma cells. We demonstrate that temsirolimus and torin 1 effectively reduced the constitutive as well as phorbol-myristate-acetate/ oncostatin-M-induced expression of mesenchymal markers (fibronectin, vimentin, and YKL40) and neural stem cell markers (Sox2, Oct4, nestin, and mushashi1). The inhibitors significantly abrogated the neurosphere-forming capacity induced by phorbol-myristate-acetate and oncostatin-M. Furthermore, we demonstrate that the drugs dephosphorylated signal transducer and activator transcription factor 3, a major regulator of mesenchymal and neural stem cell markers implicating the role of signal transducer and activator transcription factor 3 in the inhibitory action of these drugs. The findings demonstrate the potential of mammalian target of rapamycin inhibitors as "stemness-inhibiting drugs" and a promising therapeutic approach to target glioma stem cells.

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Brain tumour stem cells: the undercurrents of human brain cancer and their relationship to neural stem cells

Cited by 65 publications

References 165 publications

Activation of PI3K/Akt pathway by CD133-p85 interaction promotes tumorigenic capacity of glioma stem cells

Activation of PI3K/Akt pathway by CD133-p85 interaction promotes tumorigenic capacity of glioma stem cells

A cross-disciplinary approach to understanding neural stem cells in development and disease

Mammalian target of rapamycin inhibitors, temsirolimus and torin 1, attenuate stemness-associated properties and expression of mesenchymal markers promoted by phorbol-myristate-acetate and oncostatin-M in glioblastoma cells

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