Connexin 43 Reverses Malignant Phenotypes of Glioma Stem Cells by Modulating E-Cadherin

Stem Cells ◽  
2012 ◽  
Vol 30 (2) ◽  
pp. 108-120 ◽  
Author(s):  
Shi-Cang Yu ◽  
Hua-Liang Xiao ◽  
Xue-Feng Jiang ◽  
Qing-Liang Wang ◽  
Yan Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Connexin 43 ◽  
Glioma Stem Cells ◽  
E Cadherin

scholarly journals Valproic Acid Inhibits Proliferation and Reduces Invasiveness in Glioma Stem Cells Through Wnt/β Catenin Signalling Activation

Genes ◽  
2018 ◽  
Vol 9 (11) ◽  
pp. 522 ◽  
Author(s):  
Gabriele Riva ◽  
Chiara Cilibrasi ◽  
Riccardo Bazzoni ◽  
Massimiliano Cadamuro ◽  
Caterina Negroni ◽  
...  
Keyword(s):  
Stem Cells ◽  
Valproic Acid ◽  
Histone Deacetylase Inhibitors ◽  
Cell Signalling ◽  
Luciferase Reporter ◽  
Signalling Pathways ◽  
Boyden Chamber ◽  
Glioma Stem Cells ◽  
Bioinformatics Analyses ◽  
E Cadherin

Glioblastoma is the most common malignant brain tumour in adults. The failure of current therapies can be ascribed to glioma stem cells (GSCs), which can rapidly repopulate the tumour following the initial treatment. The study of histone deacetylase inhibitors, such as valproic acid (VPA), is becoming an attractive field in cancer research. However, the exact mechanisms underlying its anti-cancer effect remain to be elucidated due to its pleiotropic effects on several cell-signalling pathways. Ingenuity Pathway Analysis (IPA) bioinformatics analysis was performed on genome-wide data regarding GSCs methylome to identify the signalling pathways mainly affected by methylation changes induced by VPA. Real time PCR and luciferase reporter assay were used to better investigate VPA effects on Wnt/β-catenin signalling pathway. VPA effect on GSC proliferation was evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) and Trypan blue assays. Finally, VPA impact on GSC motility was demonstrated by Boyden chamber assay and further confirmed evaluating the expression levels or localisation, through western blot or immunofluorescence, of Twist1, Snail1, E-Cadherin and N-Cadherin. The bioinformatics analyses performed on GSCs methylome highlighted that Wnt/β-catenin signalling was affected by the methylation changes induced by VPA, which could influence its activation status. In particular, we pointed out a general activation of this pathway after VPA exposure, which was accompanied by an inhibitory potential on GSCs proliferation. Finally, we also proved VPA’s ability to inhibit GSCs invasion through Snail1 and Twist1 downregulation and E-Cadherin relocalisation. VPA treatment may represent a new, interesting therapeutic approach to affect GSC proliferation and motility, but further investigations are certainly needed.

scholarly journals Downregulation of E-cadherin in pluripotent stem cells triggers partial EMT

2020 ◽  
Author(s):  
C. Aban ◽  
A. Lombardi ◽  
G. Neiman ◽  
M.C. Biani ◽  
A. La Greca ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Connexin 43 ◽  
Cancer Metastasis ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Embryonic Stem Cell Differentiation ◽  
Mesenchymal Transition ◽  
E Cadherin

Epithelial to mesenchymal transition (EMT) is a critical cellular process that has been well characterized during embryonic development and cancer metastasis and it also is implicated in several physiological and pathological events including embryonic stem cell differentiation. During early stages of differentiation, human embryonic stem cells pass through EMT where deeper morphological, molecular and biochemical changes occur. Though initially considered as a decision between two states, EMT process is now regarded as a fluid transition where cells exist on a spectrum of intermediate states. In this work, using a CRISPR interference system in human embryonic stem cells, we describe a molecular characterization of the effects of downregulation of E-cadherin, one of the main initiation events of EMT, as a unique start signal. Our results suggest that the decrease and delocalization of E-cadherin causes an incomplete EMT where cells retain their undifferentiated state while expressing several characteristics of a mesenchymal-like pheno-type. Namely, we found that E-cadherin downregulation induces SNAI1 and SNAI2 upregulation, promotes MALAT1 and LINC-ROR downregulation, modulates the expression of tight junction occludin 1 and gap junction connexin 43, increases human embryonic stem cells migratory capacity and delocalize b-catenin. Altogether, we believe our results provide a useful tool to model the molecular events of an unstable intermediate state and further identify multiple layers of molecular changes that occur during partial EMT.

scholarly journals Downregulation of E-cadherin in pluripotent stem cells triggers partial EMT

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
C. E. Aban ◽  
A. Lombardi ◽  
G. Neiman ◽  
M. C. Biani ◽  
A. La Greca ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Connexin 43 ◽  
Cancer Metastasis ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Embryonic Stem Cell Differentiation ◽  
Mesenchymal Transition ◽  
E Cadherin

AbstractEpithelial to mesenchymal transition (EMT) is a critical cellular process that has been well characterized during embryonic development and cancer metastasis and it also is implicated in several physiological and pathological events including embryonic stem cell differentiation. During early stages of differentiation, human embryonic stem cells pass through EMT where deeper morphological, molecular and biochemical changes occur. Though initially considered as a decision between two states, EMT process is now regarded as a fluid transition where cells exist on a spectrum of intermediate states. In this work, using a CRISPR interference system in human embryonic stem cells, we describe a molecular characterization of the effects of downregulation of E-cadherin, one of the main initiation events of EMT, as a unique start signal. Our results suggest that the decrease and delocalization of E-cadherin causes an incomplete EMT where cells retain their undifferentiated state while expressing several characteristics of a mesenchymal-like phenotype. Namely, we found that E-cadherin downregulation induces SNAI1 and SNAI2 upregulation, promotes MALAT1 and LINC-ROR downregulation, modulates the expression of tight junction occludin 1 and gap junction connexin 43, increases human embryonic stem cells migratory capacity and delocalize β-catenin. Altogether, we believe our results provide a useful tool to model the molecular events of an unstable intermediate state and further identify multiple layers of molecular changes that occur during partial EMT.

The Heterogeneity of Glioma Stem Cells

2015 ◽  
Vol 9 (2) ◽  
pp. 70-77
Author(s):  
Suojun Zhang ◽  
Feng Wan ◽  
Lin Han ◽  
Fei Ye ◽  
Dongsheng Guo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Glioma Stem Cells

CDK8 maintains stemness and tumorigenicity of glioma stem cells by regulating the c-MYC pathway

Oncogene ◽  
2021 ◽  
Author(s):  
Kazuya Fukasawa ◽  
Takuya Kadota ◽  
Tetsuhiro Horie ◽  
Kazuya Tokumura ◽  
Ryuichi Terada ◽  
...  
Keyword(s):  
Stem Cells ◽  
Glioma Stem Cells
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