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LSD1-directed therapy affects glioblastoma tumorigenicity by deregulating the protective ATF4-dependent integrated stress response [RNA-seq]

ABSTRACT: LSD1-directed therapy affects glioblastoma tumorigenicity by deregulating the protective ATF4-dependent integrated stress response [RNA-seq]

PROVIDER: PRJNA751987 | ENA |

REPOSITORIES: ENA

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LSD1-directed therapy affects glioblastoma tumorigenicity by deregulating the protective ATF4-dependent integrated stress response

Project description:LSD1-directed therapy affects glioblastoma tumorigenicity by deregulating the protective ATF4-dependent integrated stress response

| PRJNA751881 | ENA

LSD1-directed therapy affects glioblastoma tumorigenicity by deregulating the protective ATF4-dependent integrated stress response [ChIP-seq]

Project description:Tumor-initiating cells (TICs) play a critical role in glioblastoma (GBM) maintenance being responsible for its heterogeneity and resistance to standard therapy. A step toward clinical translation includes GBM TIC targeting. Among the molecules tested for GBM treatment, are those targeting epigenetic modifiers. By using patient-derived TICs and xenograft orthotopic models, we identified Lysine-specific histone demethylase 1A (LSD1) as a potentially druggable target in GBM. LSD1-directed therapy by means of the selective, orally bioavailable and brain penetrant inhibitor DDP_38003 effectively impairs growth, stem-like features and tumorigenic potential of GBM TICs. Our findings point to LSD1 as a positive regulator of Activating Transcription Factor 4 (ATF4)-dependent response in all stress conditions arising during tumor growth and therapy. Thus, through the downregulation of either ATF4 and its adaptive genes, LSD1 targeting is likely a promising strategy to hit GBM TICs by counteracting the ATF4-mediated adaptation to stress.

2022-01-10 | GSE181372 | GEO

LSD1-directed therapy affects glioblastoma tumorigenicity by deregulating the protective ATF4-dependent integrated stress response [RNA-seq]

2022-01-10 | GSE181378 | GEO

LSD1-directed therapy affects glioblastoma tumorigenicity by deregulating the protective ATF4-dependent integrated stress response [ATAC-seq]

2022-01-10 | GSE181366 | GEO

LSD1-directed therapy affects glioblastoma tumorigenicity by deregulating the protective ATF4-dependent integrated stress response [ATAC-seq]

Project description:LSD1-directed therapy affects glioblastoma tumorigenicity by deregulating the protective ATF4-dependent integrated stress response [ATAC-seq]

| PRJNA751856 | ENA

LSD1-directed therapy affects glioblastoma tumorigenicity by deregulating the protective ATF4-dependent integrated stress response [ChIP-seq]

Project description:LSD1-directed therapy affects glioblastoma tumorigenicity by deregulating the protective ATF4-dependent integrated stress response [ChIP-seq]

| PRJNA751852 | ENA

LSD1-directed therapy affects glioblastoma tumorigenicity by deregulating the protective ATF4-dependent integrated stress response

Project description:Despite the progress in medicine, no significant advancement in the standard of care for glioblastoma (GBM) patients have been reached. GBM heterogeneity, poor blood–brain barrier penetration and resistance to therapy highlight the need for new targets and clinical treatments. A step toward clinical translation includes the eradication of GBM Tumor-Initiating Cells (TICs), responsible for GBM heterogeneity and relapse. By using patient-derived TICs and xenograft orthotopic models, we demonstrate that Lysine-specific histone demethylase 1A (LSD1) is a druggable target in GBM. Here, we analyze the effect of LSD1i treatment on histone H3K4 in primary human cells and mouse brains.

2022-04-14 | PXD025781 | Pride

LSD1-directed therapy affects glioblastoma tumorigenicity by deregulating the protective ATF4-dependent integrated stress response

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-01-10 | GSE181379 | GEO

Effect of muscle-specific ATF4 gene knockout (ATF4 mKO) on skeletal muscle mRNA levels in aged mice.

Project description:For additional details see Ebert et al, Identification and Small Molecule Inhibition of an ATF4-dependent Pathway to Age-related Skeletal Muscle Weakness and Atrophy. Quadriceps femoris muscles were harvested from 22-month-old muscle-specfic ATF4 knockout (ATF4 mKO) mice and littermate controls. mRNA levels in ATF4 mKO muscles were normalized to levels in littermate control muscles.

2015-09-03 | E-GEOD-72658 | biostudies-arrayexpress

Overexpression of ATF4 in BEAS2B cells

Project description:To determine gene expression changes induced by ATF4 overexpression, RNA was isolated from BEAS2B cells after overexpression of ATF4 or negative control. mRNA expression was profiled using Affymetrix Human Gene 1.0 ST Arrays. RNA isolated from BEAS2B cells after overexpression of ATF4 or empty vector was processed and hybridized to Affymetrix Human Gene 1.0 ST Arrays. Experiments were performed in triplicate. Data from the 6 microarrays were used for RMA normalization. RMA normalization was performed in the R statsitical environment using the affy package. A t-test was used to determine the association of gene expression with ATF4 overexpression.

2013-05-01 | E-GEOD-45949 | biostudies-arrayexpress

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