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Genetic dependencies associated with transcription factor activities in human cancer cell lines [CROP-seq]

ABSTRACT: Transcription factors (TFs) are important mediators of aberrant transcriptional programs in cancer cells. In this study, we focused on TF activity (TFa) as a new biomarker for cell line-selective anti-proliferative effects, in that high TFa predicts sensitivity to loss-of-function of a given gene (i.e., genetic dependencies (GD)). Our linear regression-based framework identified 3,047 pan-cancer and 3,952 cancer-typespecific candidate TFa-GD associations from cell line data, which were then crossexamined for impact on survival in patient cohorts. One of the most prominent biomarkers was TEAD1 activity, whose associations with its predicted GDs were validated through experimental evidence as proof of concept. Overall, these TFa-GD associations represent an attractive resource for identifying innovative, biomarkerdriven hypotheses for drug discovery programs in oncology.

ORGANISM(S): Homo sapiens

PROVIDER: GSE263747 | GEO | 2024/04/29

REPOSITORIES: GEO

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Genetic dependencies associated with transcription factor activities in human cancer cell lines [SLAM-seq]

Project description:Transcription factors (TFs) are important mediators of aberrant transcriptional programs in cancer cells. In this study, we focused on TF activity (TFa) as a new biomarker for cell line-selective anti-proliferative effects, in that high TFa predicts sensitivity to loss-of-function of a given gene (i.e., genetic dependencies (GD)). Our linear regression-based framework identified 3,043 pan-cancer and 3,952 cancer-type-specific candidate TFa-GD associations from cell line data, which were then cross-examined for impact on survival in patient data. One of the most prominent biomarkers was TEAD1 activity, whose associations with its predicted GDs were validated through experimental evidence as proof of concept. Overall, these TFa-GD pairs represent an attractive resource for identifying innovative, biomarker-driven hypotheses for drug discovery programs in oncology.

2024-04-29 | GSE254799 | GEO

Gene expression profile of YAP1, TEAD1 and KLF5 in hepatocellular carcinoma cell line (SK-Hep1)

Project description:Hippo signaling pathway is pivotally involved in human cancer. Among the Hippo components, YAP1 is highly active while function of MST1,2 and SAV1 was lost in liver cancer. Based on systematic analysis, we identified KLF5 as YAP1 binding partner in silico. To investigate KLF5 in liver cancer, we performed the gene expression microarray after knocked down YAP1, TEAD1 and KLF5 in SK-Hep1 cell line. To identify the role of YAP1, TEAD1 and KLF5 in hepatocellular carcinoma cell line, we performed microarray after knocking down YAP1, TEAD1 and KLF5 in hepatocellular carcinoma cell line (3 siLuc, 3 siYAP1, 3 siTEAD1, 3 siKLF5)

2013-12-31 | E-GEOD-32597 | biostudies-arrayexpress

G-CSF reshapes the cytosolic PCNA scaffold and modulates glycolysis in neutrophils

Project description:The balance between neutrophil survival and apoptosis must be tightly regulated to avoid exaggerated inflammatory responses. Cytosolic proliferating cell nuclear antigen (PCNA) is involved in neutrophil survival and function, where it acts as a scaffold and associates with proteins involved in NADPH oxidase activation, cytoskeletal dynamics and metabolism. While the PCNA interactome has been characterized in neutrophils under homeostatic conditions, less is known about neutrophil PCNA in pathophysiological contexts. G-CSF is a cytokine produced in response to inflammatory stimuli, that regulates many aspects of neutrophil biology. Here we used neutrophils from G-CSF-treated haemopoietic stem cell donors (GD) as a model to understand the role of PCNA during inflammation. Proteomic analysis of the neutrophil cytosol revealed significant differences between GD and healthy donors (HD). PCNA was one of the most upregulated proteins in GD and the PCNA interactome was significantly different in GD compared to HD. Importantly, while PCNA associated with almost all enzymes involved in glycolysis in HD, these associations were decreased in GD. Functionally, neutrophils from GD had a significant increase in glycolysis compared to HD. Using p21 competitor peptides, we showed that PCNA negatively regulates neutrophil glycolysis in HD, but had no effect on GD neutrophils. These data demonstrate that G-CSF alters the PCNA scaffold, affecting interactions with key glycolytic enzymes and thus regulates glycolysis, the main energy pathway utilized by neutrophils. Taken together, we show PCNA is a key protein involved in neutrophil survival and glycolysis and may be instrumental in the reprogramming that neutrophils undergo in inflammatory or tumoral settings.

2024-02-15 | PXD043496 | Pride

YAP1 exerts its transcriptional control via TEAD mediated activation of enhancers

Project description:YAP is the principle effector of the Hippo signaling pathway; a key regulator of tissue homeostasis whose dysregulation is linked to cancer development. YAP regulation of gene expression is thought to involve the TEAD transcription factor family. Here we show that YAP and TEAD1 binding always co-occurs and is mediated by single as well as double TEAD1 motifs with a particular 3bp spacer (CATTCCNNNCATTCC). This suggests that YAP activity appears exclusively mediated by TEAD1. Despite being characterized as a promoter-binding factor YAP/TEAD actually binds predominantly to enhancers. Moreover we show that YAP is necessary for activity of the linked gene and proper chromatin state of regulated enhancers. These results establish mode of binding and activation of YAP mediated nuclear response of the Hippo pathway by TEAD1 and provide a comprehensive list and a novel class of direct target genes that are regulated distally and could be exploited for cancer therapeutics. Sequencing of ChIP and input samples for YAP1 and TEAD1 transcription factors and H3K27ac histone modification in SF268 glioblastoma cells and for YAP1 transcription factor in NCI-H2052 mesothelioma cells.

2015-08-25 | E-GEOD-61852 | biostudies-arrayexpress

Transcriptional profiling of glucose deprivation resistant and glucose deprivation sensitive clones derived from IGROV-1 and SKOV3 ovarian cancer models and cultivated under either normal-glucose or low-glucose condition

Project description:This microarray experiment was designed to identify genes and pathways modulated in glucose deprivation resistant (GDR) and glucose deprivation sensitive (GDS) clones of ovarian cancer xenografts. Tumors were established in NOD/SCID mice by s.c. injection of human ovarian cancer cells (IGROV-1 and SKOV3). After sacrifice GDR and GDS clones were obtained from ex vivo cultures of tumors. Once isolated, GDR and GDS clones were cultivated in normal-glucose (0h) or low-glucose condition (6 h and 24 h). Two different time points were selected to investigate both early (6 h) and late (24 h) transcriptional effects of glucose deprivation in IGROV-1 and SKOV3-derived clones. Total RNA was extracted from samples and hybridized on Affymetrix GeneChip™ PrimeView™ Human Gene Expression Arrays. Based on assessment of RNA quality and on quality control analyses (including MAplots and boxplots), only one sample, corresponding to GDR condition at 6 h of glucose deprivation in SKOV3 model, was excluded because it was deemed not suitable for data analysis. In order to evaluate the effects of glucose deprivation in the two models, expression data of IGROV-1 and SKOV3-derived GDR and GDS clones were normalized and analyzed separately. Raw microarray data and pre-processed data matrices are available together with the applied protocols. Results of differential expression analysis are provided as supplementary tables of the associated publication.

2023-05-31 | E-MTAB-12150 | biostudies-arrayexpress

Gene expression profile of YAP1, TEAD1 and KLF5 in hepatocellular carcinoma cell line (SK-Hep1)

2013-12-31 | GSE32597 | GEO

Surface CD52, CD84 and PTGER2 mark mature PMN-MDSCs from cancer patients and G-CSF-treated donors [scRNA-seq]

Project description:In this study, we reported the identification of a specific gene signature expressed by mPMN-MDSCs from NSCLC/HNC patients and G-CSF-treated donor (GDs) by bulk-RNA-seq that clearly reflects their metabolic/functional reprogramming. ScRNA-seq experiments further confirmed that the mPMN-MDSC gene signature is significantly enriched in both mNDNs/mLDNs from GDs

2024-03-07 | GSE250001 | GEO

Surface CD52, CD84 and PTGER2 mark mature PMN-MDSCs from cancer patients and G-CSF-treated donors [bulk RNA-seq]

2024-03-07 | GSE191254 | GEO

Gene expression from Gaucher Disease iPSc

Project description:Gene expression data obtained from induced pluripotent stem cells derived from wild type fibroblasts (iPSc WT) and from Gaucher Disease type 2 fibroblasts (GD iPSc). Also, gene expression analysis from the initial fibroblasts was made (WT fibroblasts and GD- fibroblasts), as well as gene expression analysis from a human embryonic stem cell line (hES4).

2012-12-07 | GSE41243 | GEO

Control ChIP-seq from K562 (ENCSR532KDW)

Project description:K562 immortalized cell line stably expressing C-terminal eGFP-TEAD1 fusion protein. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf

2021-03-30 | GSE170514 | GEO

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