Pediatric hemispheric high-grade glioma: targeting the future

Coleman, Christina; Stoller, Schuyler; Grotzer, Michael A.; Stücklin, Ana S. Guerreiro; Nazarian, Javad; Mueller, Sabine

doi:10.1007/s10555-020-09850-5

Cited by 25 publications

(28 citation statements)

References 116 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In adults, glioblastoma represents more than half of all gliomas, and it is characterized by aggressive malignant phenotypes, poor prognosis, and low survival rates (Westermark, 2012;Omuro and DeAngelis, 2013). The 5-year survival rate of adult glioblastoma is of 2%, and pediatric glioblastoma is <20% (Hanif et al, 2017;Coleman et al, 2020). Currently ChIP-qPCR assays were performed again using G9a antibodies to map the G9a-binding locus region.…”

Section: Discussionmentioning

confidence: 99%

Deficiency of G9a Inhibits Cell Proliferation and Activates Autophagy via Transcriptionally Regulating c-Myc Expression in Glioblastoma

Zhang

Zhong

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Glioblastoma is an aggressive and difficult to treat cancer. Recent data have emerged implicating that histone modification level may play a crucial role in glioma genesis. The histone lysine methyltransferase G9a is mainly responsible for the mono- and di-methylation of histone H3 lysine 9 (H3K9), whose overexpression is associated with a more aggressive phenotype in cancer. However, the detailed correlations between G9a and glioblastoma genesis remain to be further elucidated. Here, we show that G9a is essential for glioblastoma carcinogenesis and reveal a probable mechanism of it in cell proliferation control. We found that G9a was highly expressed in glioblastoma cells, and knockdown or inhibition of G9a significantly repressed cell proliferation and tumorigenesis ability both in vitro and in vivo. Besides, knockdown or inhibition of G9a led to a cell cycle arrest in G2 phase, as well as decreased the expression of CDK1, CDK2, Cyclin A2, and Cyclin B1, while it induced the activation of autophagy. Further investigation showed that G9a deficiency induced cell proliferation suppression, and activation of autophagy was rescued by overexpression of the full-length c-Myc. Chromatin immunoprecipitation (ChIP) assay showed that G9a was enriched on the −2267 to −1949 region of the c-Myc promoter in LN-229 cells and the −1949 to −1630 region of the c-Myc promoter in U-87 MG cells. Dual-luciferase reporter assay showed that c-Myc promoter activity was significantly reduced after knockdown or inhibition of G9a. Our study shows that G9a controls glioblastoma cell proliferation by transcriptionally modulating oncogene c-Myc and provides insight into the capabilities of G9a working as a potential therapeutic target in glioblastoma.

show abstract

Section: Discussionmentioning

confidence: 99%

Deficiency of G9a Inhibits Cell Proliferation and Activates Autophagy via Transcriptionally Regulating c-Myc Expression in Glioblastoma

Zhang

Zhong

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…Gliomas are tumours that arise from glial precursor cells originating from the brain and the spinal cord. These glial neoplasms comprise a sizeable group of tumours that can be classified into histological, molecular and clinicopathologic subtypes [ 1 ]. Gliomas are classified as low grade (WHO grade I/II) and high grade (WHO grade III/IV), with glioblastoma (multiforme) (GBM) being an aggressive malignant WHO grade IV astrocytoma.…”

Section: Gliomamentioning

confidence: 99%

Ion Channels as Therapeutic Targets in High Grade Gliomas

Griffin

Khan

Basu

et al. 2020

Cancers

View full text Add to dashboard Cite

Glioblastoma multiforme (GBM) is a lethal brain cancer with an average survival of 14–15 months even with exhaustive treatment. High grade gliomas (HGG) represent the leading cause of CNS cancer-related death in children and adults due to the aggressive nature of the tumour and limited treatment options. The scarcity of treatment available for GBM has opened the field to new modalities such as electrotherapy. Previous studies have identified the clinical benefit of electrotherapy in combination with chemotherapeutics, however the mechanistic action is unclear. Increasing evidence indicates that not only are ion channels key in regulating electrical signaling and membrane potential of excitable cells, they perform a crucial role in the development and neoplastic progression of brain tumours. Unlike other tissue types, neural tissue is intrinsically electrically active and reliant on ion channels and their function. Ion channels are essential in cell cycle control, invasion and migration of cancer cells and therefore present as valuable therapeutic targets. This review aims to discuss the role that ion channels hold in gliomagenesis and whether we can target and exploit these channels to provide new therapeutic targets and whether ion channels hold the mechanistic key to the newfound success of electrotherapies.

show abstract

“…9 Targeted therapies, such as EGFR inhibitors, have been and continue to be evaluated in pHGG and so far have not become part of standard care. 10…”

Section: Current Treatment For Pediatric Cns Tumors: Medulloblastomamentioning

confidence: 99%