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Global profiling of cancer cell recovery from therapy-induced stress reveals druggable vulnerabilities

ABSTRACT: Global profiling of cancer cell recovery from therapy-induced stress reveals druggable vulnerabilities

PROVIDER: PRJNA665050 | ENA |

REPOSITORIES: ENA

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Global profiling of cancer cell recovery from therapy-induced stress reveals druggable vulnerabilities

Project description:Cancer cells survive therapy-induced stress, but how they resolve it is not clear. Using an integrated systems level approach we delineate the global mechanisms of cellular recovery from proteotoxic stress. Our findings in proteasome inhibitor-treated myeloma cells provide a layered chart of the protracted processes of stress resolution that encompass extensive metabolic changes. Tumour cells that have survived proteasome inhibition and are recovering from proteotoxic injuries are more vulnerable to certain insults than acutely stressed or unstressed cells. We identify mitochondria and the GCN2-driven cellular response to amino acid depletion as examples of recovery-associated vulnerabilities, and demonstrate that GCN2 is a bona fide target in transcriptional signature-defined subsets of solid cancers irrespective of prior proteasome inhibition. Thus, targeting multi-system vulnerabilities tied to cellular recovery from drug-induced stress has the potential to optimise cancer therapies.

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Enhancer remodeling promotes resistance to epigenetic-targeted therapy and engenders tumor cell vulnerabilities

Project description:Enhancer remodeling promotes resistance to epigenetic-targeted therapy and engenders tumor cell vulnerabilities

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Medicago truncatula drought stress recovery

Project description:Molecular Elasticity and Adjustment of Drought Recovery Dynamics of 14N- and 15N-fertilized Legume Medicago truncatula. Climate change in conjunction with population growth necessitates a systems biology approach to characterize plant drought response and a more thorough understanding of the underlying molecular mechanisms. During drought stress and recovery, the metabolome and proteome regulate and are regulated through diverse mechanisms including synthesis and degradation. In order to study this complex regulation network, a front-end multilevel analysis is presented for the first time, investigating protein turnover, regulatory classes of proteins and metabolites as well as post translational ubiquitination of a target set of proteins during a severe stress and recovery scenario in the model legume Medicago truncatula. Evidence for enhanced translational proteome regulation was observed during drought recovery and functional clusters of differentially dynamic phases during the course of recovery were defined. The data give novel insights into molecular elasticity that enable recovery of drought stressed plants. Additionally, these results offer putative targets and metabolic pathways for future plant-bioengineering towards enhanced drought stress tolerance.

2016-03-29 | PXD001728 | Pride

Gene expression profile in yeast under physiological changes of stress adaptation and stress recovery

Project description:The data provide information expression profile in yeast for 5 different physioloigcal conditions during stress adpatation and stress recovery (normal growth, during stress adaptation, after stress adaptation, under stress recovery, after stress recovery) in yeast. The purpose of the study is to understand how histone acetyltransferase HATs (Gcn5) apply it is function in gene regulation by changing global or local histone acetylation level under different physiological conditions. Gene expression levels measured for at 5 different time points of physiological changes under stress adaptation and stress recovery.

2013-07-22 | E-GEOD-36599 | biostudies-arrayexpress

Gene expression profile in yeast under physiological changes of stress adaptation and stress recovery

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Chemical Proteomics Identifies Druggable Vulnerabilities in a Genetically Defined Cancer.

Project description: Not available

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Mexican maize landraces under drought stress and recovery irrigation

Project description:Transcriptional profiling of three mexican maize landraces under 10, and 17 days stress and recovery irrigation

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Genome-wide enrichment of Gcn5 and H3K18/H4K16 acetylation under physiological change of stress adaptation and stress recovery

Project description:The data provide information of Gcn5 enrichment, H3K18 and H4K16 acetylation level and Histone H3 density for 5 different physioloigcal conditions during stress adpatation and stress recovery (normal growth, during stress adaptation, after stress adaptation, under stress recovery, after stress recovery) in yeast. The purpose of the study is to understand how histone acetyltransferase HATs (Gcn5) apply it is function in gene regulation by changing global or local histone acetylation level under different physiological conditions. Gcn5 enrichment, H3K18 and H4K16 acetylation level and Histone H3 density are mearured and compared to input signal for 5 different physioloigcal conditions (normal growth, during stress adaptation, after stress adaptation, under stress recovery, after stress recovery). Replicates are used.

2013-07-22 | E-GEOD-36600 | biostudies-arrayexpress

CSNK1A1, KDM2A, and LTB4R2 Are New Druggable Vulnerabilities in Lung Cancer.

Project description: Not available

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

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2022-04-14 | PXD025781 | Pride

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