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EAG2 potassium channel with evolutionarily conserved function as a brain tumor target

ABSTRACT: Microarray profiling of amplified total RNA isolated from FACS-sorted Drosophila neuroblasts 2 samples per group, RNA isolated and amplified. Hybridized as a one color experiment.

ORGANISM(S): Drosophila melanogaster

SUBMITTER: Charlie Kim

PROVIDER: E-GEOD-70647 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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EAG2 potassium channel with evolutionarily conserved function as a brain tumor target

Project description:Microarray profiling of amplified total RNA isolated from FACS-sorted Drosophila neuroblasts

2015-08-09 | GSE70647 | GEO

Transcriptome analysis of Drosophila neural stem cells reveals a transcriptional network for self-renewal.

Project description:Drosophila neuroblasts have emerged as a model for stem cell biology that is ideal for genetic analysis but is limited by the lack of cell-type specific gene expression data. Here, we describe a methodology to isolate large numbers of pure neuroblasts and differentiating neurons that retain both cell cycle and lineage characteristics. We determine transcriptional profiles by mRNA sequencing and identify 28 predicted neuroblast specific transcription factors, which can be arranged in a network containing hubs for Notch signaling, growth control and chromatin regulation. Overexpression and RNAi for these factors identify Klumpfuss as a regulator of self-renewal. We show that loss of Klu function causes premature differentiation while overexpression results in the formation of transplantable brain tumors. Our data represent a valuable resource for Drosophila developmental neurobiology and we describes methodology that can be applied to other invertebrate stem cell lineages as well. comparison of transcriptomes of Drosophila melanogaster larval neuroblasts and their differentiated daughter cells (neurons)

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Transcription profiling of GR-N-91 neuroblasts injected subcutaneously into nude mice and a primary tumor Xenograft (PTX) was isolated whilst metastatic neuroblasts were isolated from Myocardium (MY) and Bone Marrow (BM)

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2006-09-11 | E-TABM-44 | biostudies-arrayexpress

Ecdysone and Mediator trigger a metabolic switch uncoupling cell cycle from cell growth to end proliferation in Drosophila neural stem cells

Project description:Stem cells are highly abundant and proliferate rapidly during early development but become a rare population in most adult organs. The molecular mechanisms causing stem cells to exit proliferation at a specific time are not well understood. Here, we show that changes in energy metabolism induced by the steroid hormone Ecdysone initiate an irreversible cascade of events leading to cell cycle exit in Drosophila neural stem cells. We show that the timely induction of oxidative phosphorylation and the mitochondrial respiratory chain are required in neuroblasts to uncouple cell cycle progression from cell growth. This results in a progressive reduction in neuroblast cell size and ultimately in terminal differentiation. Neuroblasts isolated from brain tumors fail to undergo this shrinkage process and this may explain why they are immortalized. Our findings show that cell size control can be modified by systemic hormonal signaling and reveal a unique connection between metabolism and proliferation control in stem cells. Comparison of transcriptomes of Drosophila melanogaster central brain NBs from wild-type larval NBs, wild type pupal NBs and med27 RNAi pupal NBs.

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EAG2 potassium channel with evolutionarily conserved function as a brain tumor target

Project description:Characterizing the impact of pharmacological and shRNA-mediated silencing of EAG2 in medulloblastoma. A medulloblastoma (MB) cell line was untreated, mock(DMSO)-treated and treated to inhibit EAG2 (both pharmacologically and via shRNA).

2015-07-08 | E-GEOD-70576 | biostudies-arrayexpress

EAG2 potassium channel with evolutionarily conserved function as a brain tumor target

Project description:Characterizing the impact of pharmacological and shRNA-mediated silencing of EAG2 in medulloblastoma. Medulloblastoma (MB) is the most common pediatric CNS malignancy. Previously, we demonstrated that overexpression of the ion channel EAG2, identified in a subset of histological and molecular subtypes of this disease, functionally contributes to tumor progression (PMID: 22855790). Here, we demonstrate the evolutionarily conserved function of EAG2 potassium channel in promoting brain tumor growth and metastasis, delineate downstream pathways and uncover a co-option mechanism for different potassium channels to regulate mitotic cell volume and tumor progression. We show that EAG2 potassium channel is enriched at the trailing edge of migrating MB cells to regulate local cell volume dynamics, thereby facilitating cell motility. We identify the FDA- approved antipsychotic drug thioridazine as an EAG2 channel blocker that reduces xenografted MB growth and metastasis, and present a case report of repurposing thioridazine for treating a human patient. Our findings thus illustrate the potential of targeting ion channels in cancer treatment.

2015-07-08 | GSE70576 | GEO

EAG2 potassium channel with evolutionarily conserved function as a brain tumor target.

Project description:Over 20% of the drugs for treating human diseases target ion channels, but no cancer drug approved by the US Food and Drug Administration (FDA) is intended to target an ion channel. We found that the EAG2 (Ether-a-go-go 2) potassium channel has an evolutionarily conserved function for promoting brain tumor growth and metastasis, delineate downstream pathways, and uncover a mechanism for different potassium channels to functionally cooperate and regulate mitotic cell volume and tumor progression. EAG2 potassium channel was enriched at the trailing edge of migrating medulloblastoma (MB) cells to regulate local cell volume dynamics, thereby facilitating cell motility. We identified the FDA-approved antipsychotic drug thioridazine as an EAG2 channel blocker that reduces xenografted MB growth and metastasis, and present a case report of repurposing thioridazine for treating a human patient. Our findings illustrate the potential of targeting ion channels in cancer treatment.

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When Is a Potassium Channel Not a Potassium Channel?

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Potassium channel regulation.

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Neutrophils promote M2 polarization of macrophages during Nippostrongylus brasiliensis infection

Project description:Microarray profiling of amplified total RNA isolated from macrophages sorted from naïve or Nb-infected mice treated with neutrophil-depleting or control antibodies. 4 independent replicates collected from each treatment/infection group. RNA isolated and amplified from FACS-sorted macrophages. Hybridized as a one color experiment.

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