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 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 Pentraxin-3 Modulates Osteogenic/Odontogenic Differentiation and Migration of Human Dental Pulp Stem Cells

2019 ◽  
Vol 20 (22) ◽  
pp. 5778
Author(s):  
Yeon Kim ◽  
Joo-Yeon Park ◽  
Hyun-Joo Park ◽  
Mi-Kyoung Kim ◽  
Yong-Il Kim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Dental Pulp ◽  
Tissue Repair ◽  
Therapeutic Potential ◽  
Dental Pulp Stem Cells ◽  
Pentraxin 3 ◽  
Odontogenic Differentiation ◽  
Human Dental Pulp ◽  
And Migration

Pentraxin-3 (PTX3) is recognized as a modulator of inflammation and a mediator of tissue repair. In this study, we characterized the role of PTX3 on some biological functions of human dental pulp stem cells (HDPSCs). The expression level of PTX3 significantly increased during osteogenic/odontogenic differentiation of HDPSCs, whereas the knockdown of PTX3 decreased this differentiation. Silencing of PTX3 in HDPSCs inhibited their migration and C-X-C chemokine receptor type 4 (CXCR4) expression. Our present study indicates that PTX3 is involved in osteogenic/odontogenic differentiation and migration of HDPSCs, and may contribute to the therapeutic potential of HDPSCs for regeneration and repair.

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.

scholarly journals Critical role of Src-Syk-PLCγ2 signaling in megakaryocyte migration and thrombopoiesis

Blood ◽  
2010 ◽  
Vol 116 (5) ◽  
pp. 793-800 ◽  
Author(s):  
Alexandra Mazharian ◽  
Steve G. Thomas ◽  
Tarvinder S. Dhanjal ◽  
Christopher D. Buckley ◽  
Steve P. Watson
Keyword(s):  
Kinase Inhibitor ◽  
Tyrosine Phosphatase ◽  
Critical Role ◽  
Src Family Kinases ◽  
Surface Glycoprotein ◽  
Platelet Recovery ◽  
Glycoprotein Vi ◽  
Syk Kinase ◽  
And Migration

Migration of megakaryocytes (MKs) from the proliferative osteoblastic niche to the capillary-rich vascular niche is essential for proplatelet formation and platelet release. In this study, we explore the role of surface glycoprotein receptors and signaling proteins in regulating MK migration and platelet recovery after immune-induced thrombocytopenia. We show that spreading and migration of mouse primary bone marrow–derived MKs on a fibronectin matrix are abolished by the Src family kinases inhibitor PP1, the Syk kinase inhibitor R406 and the integrin αIIbβ3 antagonist lotrafiban. We also demonstrate that these responses are inhibited in primary phospholipase C γ2 (PLCγ2)–deficient MKs. Conversely, MK spreading and migration were unaltered in the absence of the collagen receptor, the glycoprotein VI–FcRγ-chain complex. We previously reported a correlation between a defect in MK migration and platelet recovery in the absence of platelet endothelial cell adhesion molecule-1 and the tyrosine phosphatase CD148. This correlation also holds for mice deficient in PLCγ2. This study identifies a model in which integrin signaling via Src family kinases and Syk kinase to PLCγ2 is required for MK spreading, migration, and platelet formation.

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

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 Ethical Implications in the Use of Embryonic and Adult Neural Stem Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Rodrigo Ramos-Zúñiga ◽  
Oscar González-Pérez ◽  
Ana Macías-Ornelas ◽  
Vivian Capilla-González ◽  
Alfredo Quiñones-Hinojosa
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Neurological Diseases ◽  
Human Condition ◽  
Ethical Implications ◽  
Technological Advances ◽  
And Migration ◽  
Risk And Benefit ◽  
Proper Balance

The advent and growth of technological advances have led to new routes of knowledge. Thereby, we currently face new challenges. We have just started to get a glimpse of the structural and functional role of neural stem cells in differentiation and migration processes, the origin of synaptic networks, and subsequent readjustments in specific circuits. A whole range of treatment possibilities originates from this knowledge that potentially can be used for different neurological diseases in humans. Although this is an encouraging scenario, it implies that the human brain is the object of such study, as well as its potential manipulation and transplantation. It is, therefore, pertinent that ethical principles should be followed in such research to have proper balance between what can be done and what should be done, according to every specific context. Hence, it is wise to consider ethical implications in every research project, along with potential clinical applications, under the principle of causing no harm, following risk and benefit rules in decision making and with respect of the human condition as a priority.

scholarly journals Targeting cancer stem cells in medulloblastoma by inhibiting AMBRA1 dual function in autophagy and STAT3 signalling

2021 ◽  
Author(s):  
Francesca Nazio ◽  
Agnese Po ◽  
Luana Abballe ◽  
Claudio Ballabio ◽  
Francesca Diomedi Camassei ◽  
...  
Keyword(s):  
Stem Cells ◽  
Genetic Alterations ◽  
Dual Function ◽  
Potential Growth ◽  
Myc Oncogene ◽  
Targeted Treatments ◽  
Group 3 ◽  
And Migration ◽  
Stat3 Signalling

AbstractMedulloblastoma (MB) is a childhood malignant brain tumour comprising four main subgroups characterized by different genetic alterations and rate of mortality. Among MB subgroups, patients with enhanced levels of the c-MYC oncogene (MBGroup3) have the poorest prognosis. Here we identify a previously unrecognized role of the pro-autophagy factor AMBRA1 in regulating MB. We demonstrate that AMBRA1 expression depends on c-MYC levels and correlates with Group 3 patient poor prognosis; also, knockdown of AMBRA1 reduces MB stem potential, growth and migration of MBGroup3 stem cells. At a molecular level, AMBRA1 mediates these effects by suppressing SOCS3, an inhibitor of STAT3 activation. Importantly, pharmacological inhibition of autophagy profoundly affects both stem and invasion potential of MBGroup3 stem cells, and a combined anti-autophagy and anti-STAT3 approach impacts the MBGroup3 outcome. Taken together, our data support the c-MYC/AMBRA1/STAT3 axis as a strong oncogenic signalling pathway with significance for both patient stratification strategies and targeted treatments of MBGroup3.

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