Pathway analysis of glutamate-mediated, calcium-related signaling in glioma progression

Pei, Zhe; Lee, Kuo-Chieh; Khan, Amber; Erisnor, Gabriell; Wang, Hoau Yan

doi:10.1016/j.bcp.2020.113814

Cited by 52 publications

(38 citation statements)

References 72 publications

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“…As the significantly enriched pathway (hsa04020, hsa04724) in this study, Afshari et al [ 35 ] showed that calcium signaling pathway is involved in the processes of cell proliferation, metastasis, angiogenesis, migration, and invasiveness. Moreover, glutamatergic and calcium signaling may promote glioblastoma formation by metabolic reprogramming and genetic switching or upregulate the levels intracellular Ca 2+ to increase glutamate release [ 36 ]. The role of ErbB [epidermal growth factor receptor (EGFR)] in GBM and glioma has also been extensively studied.…”

Section: Resultsmentioning

confidence: 99%

The regulatory pattern of target gene expression by aberrant enhancer methylation in glioblastoma

Zhao

Shi-jia

et al. 2021

BMC Bioinformatics

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Background Glioblastoma multiforme (GBM) is the most common and aggressive primary malignant brain tumor with grim prognosis. Aberrant DNA methylation is an epigenetic mechanism that promotes GBM carcinogenesis, while the function of DNA methylation at enhancer regions in GBM remains poorly described. Results We integrated multi-omics data to identify differential methylation enhancer region (DMER)-genes and revealed global enhancer hypomethylation in GBM. In addition, a DMER-mediated target genes regulatory network and functional enrichment analysis of target genes that might be regulated by hypomethylation enhancer regions showed that aberrant enhancer regions could contribute to tumorigenesis and progression in GBM. Further, we identified 22 modules in which lncRNAs and mRNAs synergistically competed with each other. Finally, through the construction of drug-target association networks, our study identified potential small-molecule drugs for GBM treatment. Conclusions Our study provides novel insights for understanding the regulation of aberrant enhancer region methylation and developing methylation-based biomarkers for the diagnosis and treatment of GBM.

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Section: Resultsmentioning

confidence: 99%

The regulatory pattern of target gene expression by aberrant enhancer methylation in glioblastoma

Zhao

Shi-jia

et al. 2021

BMC Bioinformatics

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“…Studies have shown that the GABAB signaling pathway participates in the occurrence of GBM through metabolic reprogramming and genetic transformation and accelerates the replication and progression of glioma. GABAB can upregulate cytoskeleton protein and intracellular Ca 2+ level and increase the release of glutamate, so as to promote the formation of synaptic-like connection and the surrounding cell microenvironment [20]. GHB (4-hydroxybutyrate) exists in human brain and can act on GABA receptor (GABABR).…”

Section: Discussionmentioning

confidence: 99%

Mechanism of Baclofen Inhibiting the Proliferation and Metastasis of GBM by Regulating YAP

Zhu

Lü

Bao

et al. 2021

Journal of Chemistry

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This study explores the effect of baclofen on the malignant phenotype of glioblastoma (GBM) and the growth of xenograft tumors and investigates the related mechanisms, aiming to reveal the effect of baclofen on the occurrence and development of GBM. The development of new therapeutic drugs for GBM lays a theoretical and experimental foundation. Research results show that baclofen could inhibit GBM cell proliferation and migration and promote GBM cell apoptosis; baclofen dose- and time-dependently could induce GBM cell YAP phosphorylation. YAP participated in the effect of baclofen on GBM cell proliferation and migration inhibition. Baclofen induced YAP phosphorylation in GBM cells through the GABABR2-Gs-Lats1/2 signaling pathway. Baclofen could inhibit the expression of survivin and Bcl2. Baclofen inhibits subcutaneous tumors by inducing YAP phosphorylation in vivo.

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“…Glioma, a cancer arising from glia cells in the brain, uses glutamate as an autocrine or paracrine signal to promote cellular migration and invasion [74]. Results from a recent study by Pei et al indicate that glutamatergic signaling may provide positive feedback through metabolic reprogramming and genetic switching to accelerate glioma duplication and progression [75]. Glioma cells release excess glutamate through the xCT antiporter, which causes the excitotoxic death of neurons and permits tumor-cell expansion [76,77].…”

Section: Cancer Cells Amplify the Release Of Extracellular Glutamatementioning

confidence: 99%

Metabolic Signaling Cascades Prompted by Glutaminolysis in Cancer

Shah

Chen

2020

Cancers

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Aberrant glutamatergic signaling has been implicated in altered metabolic activity and the demand to synthesize biomass in several types of cancer including melanoma. In the last decade, there has been a significant contribution to our understanding of metabolic pathways. An increasing number of studies are now emphasizing the importance of glutamate functioning as a signaling molecule and a building block for cancer progression. To that end, our group has previously illustrated the role of glutamatergic signaling mediated by metabotropic glutamate receptor 1 (GRM1) in neoplastic transformation of melanocytes in vitro and spontaneous development of metastatic melanoma in vivo. Glutamate, the natural ligand of GRM1, is one of the most abundant amino acids in humans and the predominant excitatory neurotransmitter in the central nervous system. Elevated levels of glutaminolytic mitochondrial tricarboxylic acid (TCA) cycle intermediates, especially glutamate, have been reported in numerous cancer cells. Herein, we highlight and critically review metabolic bottlenecks that are prevalent during tumor evolution along with therapeutic implications of limiting glutamate bioavailability in tumors.

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Pathway analysis of glutamate-mediated, calcium-related signaling in glioma progression

Cited by 52 publications

References 72 publications

The regulatory pattern of target gene expression by aberrant enhancer methylation in glioblastoma

The regulatory pattern of target gene expression by aberrant enhancer methylation in glioblastoma

Mechanism of Baclofen Inhibiting the Proliferation and Metastasis of GBM by Regulating YAP

Metabolic Signaling Cascades Prompted by Glutaminolysis in Cancer

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