Connexin 30 mediated rewiring of glucose metabolism in rat C6 xenograft and grades of glioma

Jothi, Jayalakshmi; Janardhanam, Vanisree Arambakkam; Rama, Kumara

doi:10.1007/s11010-020-03757-z

Cited by 3 publications

(4 citation statements)

References 23 publications

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“…Functional reports on the other CpG‐relevant genes may also provide biological clues for the predictive ability of our risk signature. GJB6 (harboring cg03473518) encodes a tumor‐suppressive gap junction protein and may prevent GBM growth via rewiring glucose metabolism and inhibiting stemness 48,49 . KCNQ1 (harboring cg12578166) encodes a voltage‐dependent K+ channel and acts both as a target gene and regulator of the Wnt/β‐catenin pathway 50 .…”

Section: Discussionmentioning

confidence: 99%

“…GJB6 (harboring cg03473518) encodes a tumor‐suppressive gap junction protein and may prevent GBM growth via rewiring glucose metabolism and inhibiting stemness. 48 , 49 KCNQ1 (harboring cg12578166) encodes a voltage‐dependent K+ channel and acts both as a target gene and regulator of the Wnt/β‐catenin pathway. 50 Loss of KCNQ1 has been reported to exert anti‐tumor functions via promoting epithelial‐to‐mesenchymal transition (EMT) and disrupting adheren junctions in epithelial cancers.…”

Section: Discussionmentioning

confidence: 99%

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Genome‐wide DNA methylation analysis identifies potent CpG signature for temzolomide response in non‐G‐CIMP glioblastomas with unmethylated MGMT promoter: MGMT‐dependent roles of GPR81

Liang,

Wang,

Huang

et al. 2023

CNS Neurosci Ther

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PurposesTo identify potent DNA methylation candidates that could predict response to temozolomide (TMZ) in glioblastomas (GBMs) that do not have glioma‐CpGs island methylator phenotype (G‐CIMP) but have an unmethylated promoter of O‐6‐methylguanine‐DNA methyltransferase (unMGMT).MethodsThe discovery‐validation approach was planned incorporating a series of G‐CIMP−/unMGMT GBM cohorts with DNA methylation microarray data and clinical information, to construct multi‐CpG prediction models. Different bioinformatic and experimental analyses were performed for biological exploration.ResultsBy analyzing discovery sets with radiotherapy (RT) plus TMZ versus RT alone, we identified a panel of 64 TMZ efficacy‐related CpGs, from which a 10‐CpG risk signature was further constructed. Both the 64‐CpG panel and the 10‐CpG risk signature were validated showing significant correlations with overall survival of G‐CIMP−/unMGMT GBMs when treated with RT/TMZ, rather than RT alone. The 10‐CpG risk signature was further observed for aiding TMZ choice by distinguishing differential outcomes to RT/TMZ versus RT within each risk subgroup. Functional studies on GPR81, the gene harboring one of the 10 CpGs, indicated its distinct impacts on TMZ resistance in GBM cells, which may be dependent on the status of MGMT expression.ConclusionsThe 64 TMZ efficacy‐related CpGs and in particular the 10‐CpG risk signature may serve as promising predictive biomarker candidates for guiding optimal usage of TMZ in G‐CIMP−/unMGMT GBMs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Genome‐wide DNA methylation analysis identifies potent CpG signature for temzolomide response in non‐G‐CIMP glioblastomas with unmethylated MGMT promoter: MGMT‐dependent roles of GPR81

Liang,

Wang,

Huang

et al. 2023

CNS Neurosci Ther

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“…This alteration was associated with a decrease in hexokinase activity and slowed glucose uptake at the stage of phosphorylation, as GLUT1 (SLC2A1) and GLUT3 levels and localization remained unchanged. In another study using the C6 cell line in a xenograft model, expression of Cx30 (GJB6) inhibited expression of GLUT transporters, hexokinase II and pyruvate dehydrogenase kinase 1 (PDK1) [ 181 ]. Phosphorylation of the pyruvate dehydrogenase E1 subunit within the pyruvate dehydrogenase complex by PDK1 reduces its ability to oxidatively decarboxylate pyruvate during the formation of acetyl-CoA in the mitochondrial matrix, the committed step of aerobic metabolism of glucose.…”

Section: Connexins and Glucosementioning

confidence: 99%

“…Metabolic reprogramming, or inhibition of this process, affects the adaptability of cancer cells to metabolic changes in the microenvironment, Refs. [ 179 , 180 , 181 ]. ( D ) Adaptation to reduced glucose availability can lead to increased connexin expression, membrane localization and GJIC with associated increases in phenotypic qualities such as survival and invasion, Refs.…”

Section: Figurementioning

confidence: 99%

Connexins and Glucose Metabolism in Cancer

Jones

Bodenstine

2022

IJMS

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Connexins are a family of transmembrane proteins that regulate diverse cellular functions. Originally characterized for their ability to mediate direct intercellular communication through the formation of highly regulated membrane channels, their functions have been extended to the exchange of molecules with the extracellular environment, and the ability to modulate numerous channel-independent effects on processes such as motility and survival. Notably, connexins have been implicated in cancer biology for their context-dependent roles that can both promote or suppress cancer cell function. Moreover, connexins are able to mediate many aspects of cellular metabolism including the intercellular coupling of nutrients and signaling molecules. During cancer progression, changes to substrate utilization occur to support energy production and biomass accumulation. This results in metabolic plasticity that promotes cell survival and proliferation, and can impact therapeutic resistance. Significant progress has been made in our understanding of connexin and cancer biology, however, delineating the roles these multi-faceted proteins play in metabolic adaptation of cancer cells is just beginning. Glucose represents a major carbon substrate for energy production, nucleotide synthesis, carbohydrate modifications and generation of biosynthetic intermediates. While cancer cells often exhibit a dependence on glycolytic metabolism for survival, cellular reprogramming of metabolic pathways is common when blood perfusion is limited in growing tumors. These metabolic changes drive aggressive phenotypes through the acquisition of functional traits. Connections between glucose metabolism and connexin function in cancer cells and the surrounding stroma are now apparent, however much remains to be discovered regarding these relationships. This review discusses the existing evidence in this area and highlights directions for continued investigation.

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Does astrocyte gap junction protein expression differ during development in absence epileptic rats?

Köse

Özkan

Sur-Erdem

et al. 2022

Synapse

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Intercellular communication via gap junctions (GJs) has a wide variety of complex and essential functions in the CNS. In the present developmental study, we aimed to quantify the number of astrocytic GJs protein connexin 30 (Cx30) of genetic model of absence epilepsy rats from Strasbourg (GAERS) at postnatal P10, P30, and P60 days in the epileptic focal areas involved in the cortico-thalamic circuit. We compared the results with Wistar rats using immunohistochemistry and western blotting. The number of Cx30 immunopositive astrocytes per unit area were quantified for the somatosensory cortex (SSCx), ventrobasal (VB), and lateral geniculate (LGN) thalamic nuclei of the two strains and Cx30 western blot was applied to the tissue samples from the same regions. Both immunohistochemical and western blot results revealed the presence of Cx30 in all regions studied at P10 in both Wistar and GAERS animals.The SSCx, VB, and LGN of Wistar animals showed progressive increase in the number of Cx30 immunopositive labeled astrocytes from P10 to P30 and reached a peak at P30; then a significant decline was observed from P30 to P60 for the SSCx and VB. However, in GAERS Cx30 immunopositive labeled astrocytes showed a progressive increase from P10 to P60 for all brain regions studied. The immunohistochemical data highly corresponded with western blotting results. We conclude that the developmental disproportional expression of Cx30 in the epileptic focal areas in GAERS may be related to the onset of absence seizures or may be related to the neurogenesis of absence epilepsy.

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Connexin 30 mediated rewiring of glucose metabolism in rat C6 xenograft and grades of glioma

Cited by 3 publications

References 23 publications

Genome‐wide DNA methylation analysis identifies potent CpG signature for temzolomide response in non‐G‐CIMP glioblastomas with unmethylated MGMT promoter: MGMT‐dependent roles of GPR81

Genome‐wide DNA methylation analysis identifies potent CpG signature for temzolomide response in non‐G‐CIMP glioblastomas with unmethylated MGMT promoter: MGMT‐dependent roles of GPR81

Connexins and Glucose Metabolism in Cancer

Does astrocyte gap junction protein expression differ during development in absence epileptic rats?

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