Glioma‐derived cancer stem cells are hypersensitive to proteasomal inhibition

Yoo, Youngdong; Lee, Dong Hoon; Cha-Molstad, Hyunjoo; Kim, Hyungsin; Mun, Su Ran; Ji, Changhoon; Park, Seong Hye; Sung, Kyung Rim; Choi, Seung Ah; Hwang, Joonsung; Park, Deric M.; Kim, Seung Ki; Park, Kyung Jae; Kang, Sung Ho; Oh, Sang Cheul; Ciechanover, Aaron; Kim, Bo Yeon; Kwon, Yong Tae

doi:10.15252/embr.201744761

Cited by 7 publications

(7 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with the proposed model, MDM2 inhibitors PM2 and AMG232 potentiated the bortezomib response and synergistically killed GBM cells, and all three agents that modulate the apoptotic threshold, such as navitoclax, potentiated bortezomib. Our results are thus consistent with a role for p53 in the response to proteasome inhibitors, in line with Yoo et al (2017), Asklund et al (2012), and Forte et al (2019), but imply substantial quantitative and phenotypic differences in the response to proteasome inhibition. Further work, including quantitative mathematical modeling, will be needed to elucidate these differences and to chart the relative contributions of aberrations in p53 and CDKN2A/B, respectively.…”

Section: Discussionsupporting

confidence: 92%

A Patient-Derived Cell Atlas Informs Precision Targeting of Glioblastoma

et al. 2020

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 92%

A Patient-Derived Cell Atlas Informs Precision Targeting of Glioblastoma

et al. 2020

View full text Add to dashboard Cite

show abstract

“…GO term enrichment analysis demonstrated that 775 downregulated DEGs were significantly enriched in functions involving cellular protein modification, regulation of cell communication, and regulation of signaling. Many studies found that the cellular protein modification, including phosphorylation, ubiquitination, and acetylation, can change the cell biology function, influence disease phenotype, affect glioma cell proliferation, invasion, and apoptosis, and regulate the development of glioma [ 15 – 17 ]. And glioma cells can regulate cell communication, through the information passed to the target cells, interact with the receptor, resulting in specific biological effect such as cell proliferation and cytoskeleton changes, and promote glioma progression and angiogenesis [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

The Identification of Key Genes and Pathways in Glioma by Bioinformatics Analysis

Liu

et al. 2017

Journal of Immunology Research

View full text Add to dashboard Cite

Glioma is the most common malignant tumor in the central nervous system. This study aims to explore the potential mechanism and identify gene signatures of glioma. The glioma gene expression profile GSE4290 was analyzed for differentially expressed genes (DEGs). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were applied for the enriched pathways. A protein-protein interaction (PPI) network was constructed to find the hub genes. Survival analysis was conducted to screen and validate critical genes. In this study, 775 downregulated DEGs were identified. GO analysis demonstrated that the DEGs were enriched in cellular protein modification, regulation of cell communication, and regulation of signaling. KEGG analysis indicated that the DEGs were enriched in the MAPK signaling pathway, endocytosis, oxytocin signaling, and calcium signaling. PPI network and module analysis found 12 hub genes, which were enriched in synaptic vesicle cycling rheumatoid arthritis and collecting duct acid secretion. The four key genes CDK17, GNA13, PHF21A, and MTHFD2 were identified in both generation (GSE4412) and validation (GSE4271) dataset, respectively. Regression analysis showed that CDK13, PHF21A, and MTHFD2 were independent predictors. The results suggested that CDK17, GNA13, PHF21A, and MTHFD2 might play important roles and potentially be valuable in the prognosis and treatment of glioma.

show abstract

“…Multiple studies have confirmed the existence of CSCs in glioma, or glioma stem cells (GSCs), which are capable of self-renewal, extensive proliferation, and multi-lineage differentiation [9,14,19]. These studies have demonstrated that the rare population of GSCs is necessary and sufficient to initiate, maintain, and recapitulate the phenotype of original glioma in immunecompromised mice, and when GSCs are eliminated from the bulk tumor mass, tumor growth is inhibited [36,37]. Therefore, GSCs could play a pivotal role in glioma development in human, and these cells seem to be a promising target for glioma therapies [38].…”

Section: Introductionmentioning

confidence: 99%

Adenovirus infection promotes the formation of glioma stem cells from glioblastoma cells through the TLR9/NEAT1/STAT3 pathway

et al. 2020

View full text Add to dashboard Cite

Background: Glioma stem cells (GSCs) are glioma cells with stemness and are responsible for a variety of malignant behaviors of glioma. Evidence has shown that signals from tumor microenvironment (TME) enhance stemness of glioma cells. However, identification of the signaling molecules and underlying mechanisms has not been completely elucidated. Methods: Human samples and glioma cell lines were cultured in vitro to determine the effects of adenovirus (ADV) infection by sphere formation, RT-qPCR, western blotting, FACS and immunofluorescence. For in vivo analysis, mouse intracranial tumor model was applied. Bioinformatics analysis, gene knockdown by siRNA, RT-qPCR and western blotting were applied for further mechanistic studies. Results: Infection of patient-derived glioma cells with ADV increases the formation of tumor spheres. ADV infection upregulated stem cell markers and in turn promoted the capacities of self-renewal and multi-lineage differentiation of the infected tumor spheres. These ADV infected tumor spheres had stronger potential to form xenograft tumors in immune-compromised mice. GSCs formation could be promoted by ADV infection via TLR9, because TLR9 was upregulated after ADV infection, and knockdown of TLR9 reduced ADV-induced GSCs. Consistently, MYD88, as well as total STAT3 and phosphorylated (p-)STAT3, were also upregulated in ADV-induced GSCs. Knockdown of MYD88 or pharmaceutical inhibition of STAT3 attenuated stemness of ADV-induced GSCs. Moreover, we found that ADV infection upregulated lncRNA NEAT1. Knockdown of NEAT1 impaired stemness of ADV-induced GSCs. Lastly, HMGB1, a damage associated molecular pattern (DAMP) that triggers TLR signaling, also upregulated stemness markers in glioma cells.

show abstract

Glioma‐derived cancer stem cells are hypersensitive to proteasomal inhibition

Cited by 7 publications

References 0 publications

A Patient-Derived Cell Atlas Informs Precision Targeting of Glioblastoma

A Patient-Derived Cell Atlas Informs Precision Targeting of Glioblastoma

The Identification of Key Genes and Pathways in Glioma by Bioinformatics Analysis

Adenovirus infection promotes the formation of glioma stem cells from glioblastoma cells through the TLR9/NEAT1/STAT3 pathway

Contact Info

Product

Resources

About