The role of glioma stem cells in glioma tumorigenesis

10.2741/4249 ◽  
2014 ◽  
Vol 19 (5) ◽  
pp. 818 ◽  
Author(s):  
Chang-lin Yin
Keyword(s):  
Stem Cells ◽  
Glioma Stem Cells

scholarly journals HAUSP Stabilizes SOX2 through Deubiquitination to Maintain Self-renewal and Tumorigenic Potential of Glioma Stem Cells

2021 ◽  
Author(s):  
Zhi Huang ◽  
Kui Zhai ◽  
Qiulian Wu ◽  
Xiaoguang Fang ◽  
Qian Huang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Glioma Stem Cells ◽  
Posttranslational Regulation ◽  
Malignant Growth ◽  
Self Renewal ◽  
Animal Survival ◽  
Promising Target ◽  
Tumorigenic Potential ◽  
Therapeutic Opportunity

Glioblastoma (GBM) is the most lethal brain tumor containing glioma stem cells (GSCs) that promote malignant growth and therapeutic resistance. The self-renewal and tumorigenic potential of GSCs are maintained by core stem cell transcription factors including SOX2. Defining the posttranslational regulation of SOX2 may offer new insights into GSC biology and potential therapeutic opportunity. Here, we discover that HAUSP stabilizes SOX2 through deubiquitination to maintain GSC self-renewal and tumorigenic potential. HAUSP is preferentially expressed in GSCs in perivascular niches in GBMs. Disrupting HAUSP by shRNA or its inhibitor P22077 promoted SOX2 degradation, induced GSC differentiation, impaired GSC tumorigenic potential, and suppressed GBM tumor growth. Importantly, pharmacological inhibition of HAUSP synergized with radiation to inhibit GBM growth and extended animal survival, indicating that targeting HAUSP may overcome GSC-mediated radioresistance. Our findings reveal an unappreciated crucial role of HAUSP in the GSC maintenance and provide a promising target for developing effective anti-GSC therapeutics to improve GBM treatment.

scholarly journals CSIG-27. PRC2-INDEPENDENT FUNCTION OF EZH2/HP1BP3 COMPLEX IN GLIOMA STEM CELLS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi49-vi50
Author(s):  
Junxia Zhang ◽  
Tianfu Yu ◽  
Ning Liu
Keyword(s):  
Stem Cells ◽  
Transcriptional Repression ◽  
Glioma Stem Cells ◽  
Independent Function ◽  
Set Domain ◽  
Heterochromatin Protein 1 ◽  
Heterochromatin Protein ◽  
Histone Lysine Methyltransferase ◽  
Lysine Methyltransferase

Abstract Glioblastoma (GBM) displays cellular and genetical heterogeneity harboring a subpopulation of glioma stem cells (GSCs). Enhancer of zeste homolog 2 (EZH2), a histone lysine methyltransferase, is the core subunit of the polycomb repressor 2 (PRC2) complex, mediates gene transcriptional repression in both normal and tumor stem cells. An oncogenic role of EZH2 as a PRC2-dependent transcriptional silencer is well established; however, non-canonical functions of EZH2 are incompletely understood. Here we found a novel oncogenic mechanism for EZH2 in a PRC2-indenpend way in GSCs. Using HPLC-MS/MS and IP assay, EZH2 bound to HP1BP3 (heterochromatin protein 1 binding protein 3), a heterochromatin-related protein, with its pre-SET domain. Overexpression of H1P3B3 enhanced the proliferation, self-renewal and temozolomide (TMZ) resistance of GBM cells. Intriguingly, H1PBP3 was up-regulated in high grade gliomas with proneural (PN) subtypes and had a high predictive value on prognosis in patients with PN gliomas. Furthermore, EZH2 and HP1BP3 co-activated the expression of WNT7B by blocking the methylation of H3K9, thereby increasing TMZ resistance and tumorigenicity of glioblastoma cells. Interestingly, inhibition of WNT7B autocrine via LGK974, a specific porcupine inhibitor, effectively reversed the TMZ resistance of both GSCs and GBM glioma cells expressing HP1BP3. Hence, targeting the PRC2-independent function of EZH2 is an effective approach to enhance the efficacy of treating GBM.

scholarly journals TMIC-01. THE DYSTROGLYCAN RECEPTOR MAINTAINS GLIOMA STEM CELLS IN THE VASCULAR NICHE

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi247-vi247
Author(s):  
Bryan Day ◽  
Justin Lathia ◽  
Zara Bruce ◽  
Kathleen Ensbey ◽  
Yi Chieh Lim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Critical Factor ◽  
Glioma Stem Cells ◽  
Structural Element ◽  
Α Subunit ◽  
Vascular Niche ◽  
Cns Neoplasms ◽  
Tumour Initiation

Abstract Glioblastomas (GBMs) are malignant central nervous system (CNS) neoplasms with a very poor prognosis. They display cellular hierarchies containing self-renewing tumourigenic glioma stem cells (GSCs) in a complex heterogeneous microenvironment. One proposed GSC niche is the extracellular matrix (ECM)-rich perivascular bed of the tumour. Here, we report that the ECM binding alpha (α) subunit of the dystroglycan (DG) receptor is expressed and functionally glycosylated on GSCs residing in the vascular niche. Glycosylated αDG is also expressed highly on the most aggressive mesenchymal-like GBM tumour tissue. Furthermore, we found that DG acts to maintain a de-differentiated stem cell-like phenotype via tight control of MAPK activation. Antibody-based blockade of αDG induces robust ERK-mediated differentiation leading to reduced GSC potential. DG was shown to be required for tumour initiation, with constitutive loss significantly delaying or preventing tumourigenic potential in-vivo. These findings reveal a central role of the DG receptor not only as a structural element but also as a critical factor in the maintenance of GSCs in the GBM vascular niche.

Targeting Role of Glioma Stem Cells for Gliobastoma Multiforme

2013 ◽  
Vol 20 (15) ◽  
pp. 1974-1984 ◽  
Author(s):  
X. Zhang ◽  
W. Zhang ◽  
X.G. Mao ◽  
H.N. Zhen ◽  
W.D. Cao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Glioma Stem Cells

scholarly journals The role of Src family kinases in growth and migration of glioma stem cells

2014 ◽  
Vol 45 (1) ◽  
pp. 302-310 ◽  
Author(s):  
XIAOSI HAN ◽  
WENBIN ZHANG ◽  
XIUHUA YANG ◽  
CRYSTAL G. WHEELER ◽  
CATHERINE P. LANGFORD ◽  
...  
Keyword(s):  
Stem Cells ◽  
Src Family Kinases ◽  
Glioma Stem Cells ◽  
And Migration

scholarly journals Abstract 3778: Uncovering the role of glioma stem cells in glioblastoma chemo-resistance and recurrence

2019 ◽  
Author(s):  
Gabriele Riva ◽  
Charles Couturier ◽  
Phuong Uyen Le ◽  
Xiaohua Yan ◽  
Yu Chang Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Glioma Stem Cells

scholarly journals Aberrations of Genomic Imprinting in Glioblastoma Formation

2021 ◽  
Vol 11 ◽  
Author(s):  
Anna Lozano-Ureña ◽  
Esteban Jiménez-Villalba ◽  
Alejandro Pinedo-Serrano ◽  
Antonio Jordán-Pla ◽  
Martina Kirstein ◽  
...  
Keyword(s):  
Stem Cells ◽  
Genomic Imprinting ◽  
Current Knowledge ◽  
Small Population ◽  
Parental Origin ◽  
Imprinted Genes ◽  
Glioma Stem Cells ◽  
Epigenetic Changes ◽  
Human Gbm

In human glioblastoma (GBM), the presence of a small population of cells with stem cell characteristics, the glioma stem cells (GSCs), has been described. These cells have GBM potential and are responsible for the origin of the tumors. However, whether GSCs originate from normal neural stem cells (NSCs) as a consequence of genetic and epigenetic changes and/or dedifferentiation from somatic cells remains to be investigated. Genomic imprinting is an epigenetic marking process that causes genes to be expressed depending on their parental origin. The dysregulation of the imprinting pattern or the loss of genomic imprinting (LOI) have been described in different tumors including GBM, being one of the earliest and most common events that occurs in human cancers. Here we have gathered the current knowledge of the role of imprinted genes in normal NSCs function and how the imprinting process is altered in human GBM. We also review the changes at particular imprinted loci that might be involved in the development of the tumor. Understanding the mechanistic similarities in the regulation of genomic imprinting between normal NSCs and GBM cells will be helpful to identify molecular players that might be involved in the development of human GBM.

scholarly journals Glioma Stem Cells and Their Microenvironments: Providers of Challenging Therapeutic Targets

2016 ◽  
Vol 2016 ◽  
pp. 1-20 ◽  
Author(s):  
Elena Codrici ◽  
Ana-Maria Enciu ◽  
Ionela-Daniela Popescu ◽  
Simona Mihai ◽  
Cristiana Tanase
Keyword(s):  
Stem Cells ◽  
Cell Biology ◽  
Malignant Gliomas ◽  
Therapy Resistance ◽  
Metabolic Reprogramming ◽  
Glioma Stem Cells ◽  
Macrophage Colony ◽  
Potential Use ◽  
Macrophage Colony Stimulation Factor

Malignant gliomas are aggressive brain tumors with limited therapeutic options, possibly because of highly tumorigenic subpopulations of glioma stem cells. These cells require specific microenvironments to maintain their “stemness,” described as perivascular and hypoxic niches. Each of those niches induces particular signatures in glioma stem cells (e.g., activation of Notch signaling, secretion of VEGF, bFGF, SDF1 for the vascular niche, activation of HIF2α, and metabolic reprogramming for hypoxic niche). Recently, accumulated knowledge on tumor-associated macrophages, possibly delineating a third niche, has underlined the role of immune cells in glioma progression,viaspecific chemoattractant factors and cytokines, such as macrophage-colony stimulation factor (M-CSF). The local or myeloid origin of this new component of glioma stem cells niche is yet to be determined. Such niches are being increasingly recognized as key regulators involved in multiple stages of disease progression, therapy resistance, immune-escaping, and distant metastasis, thereby substantially impacting the future development of frontline interventions in clinical oncology. This review focuses on the microenvironment impact on the glioma stem cell biology, emphasizing GSCs cross talk with hypoxic, perivascular, and immune niches and their potential use as targeted therapy.

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