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An ectopic network of transcription factors regulated by Hippo signaling drives growth and invasion of a malignant tumor model

ABSTRACT: An ectopic network of transcription factors regulated by Hippo signaling drives growth and invasion of a malignant tumor model

PROVIDER: PRJNA291026 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR2128010_1.fastq.gz	Fastqsanger.gz
	SRR2128010_2.fastq.gz	Fastqsanger.gz
	SRR2128020.fastq.gz	Fastqsanger.gz
	SRR2128030.fastq.gz	Fastqsanger.gz
	SRR2128011_1.fastq.gz	Fastqsanger.gz

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An ectopic network of transcription factors regulated by Hippo signaling drives growth and invasion of a malignant tumor model [larval imaginal discs]

Project description:Cancer cells have abnormal gene expression profiles, however, the transcription factors and the architecture of the regulatory network that drive cancer specific gene expression is often not known. Here we studied a model of Ras-driven invasive tumorigenesis in Drosophila epithelial tissues and combined in vivo genetics with high-throughput sequencing and computational modeling to decipher the regulatory logic of tumor cells. Surprisingly, we discovered that the bulk of the tumor specific gene expression is driven by an ectopic network of a few transcription factors that are overexpressed and/or hyperactivated in tumor cells. These factors are Stat, AP-1, the bHLH proteins Myc and AP-4, the nuclear hormone receptor Ftz-f1, the nuclear receptor coactivator Taiman/AIB1, and Mef2. Notably, many of these transcription factors are also hyperactivated in human tumors. Bioinformatics analysis predicted that these factors directly regulate the majority of the tumor specific gene expression, that they are interconnected by extensive cross-regulation, and that they show a high degree of co-regulation of target genes. Indeed, the factors of this network were required in multiple epithelia for tumor growth and invasiveness and knock-down of individual factors caused a reversion of the tumor specific expression profile, but had no observable effect on normal tissues. We further found that the Hippo pathway effector Yki/Sd was strongly activated in tumor cells and initiated cellular reprogramming by activating several transcription factors of this network. Thus, modeling regulatory networks identified an ectopic yet highly ordered network of master regulators that control tumor cell specific gene expression. RNA-seq gene expression profiling across Drosophila 3rd instar larval imaginal discs in a control and different genetic perturbations.

2016-06-10 | E-GEOD-71350 | biostudies-arrayexpress

An ectopic network of transcription factors regulated by Hippo signaling drives growth and invasion of a malignant tumor model [larval wild type discs]

Project description:Cancer cells have abnormal gene expression profiles, however, the transcription factors and the architecture of the regulatory network that drive cancer specific gene expression is often not known. Here we studied a model of Ras-driven invasive tumorigenesis in Drosophila epithelial tissues and combined in vivo genetics with high-throughput sequencing and computational modeling to decipher the regulatory logic of tumor cells. Surprisingly, we discovered that the bulk of the tumor specific gene expression is driven by an ectopic network of a few transcription factors that are overexpressed and/or hyperactivated in tumor cells. These factors are Stat, AP-1, the bHLH proteins Myc and AP-4, the nuclear hormone receptor Ftz-f1, the nuclear receptor coactivator Taiman/AIB1, and Mef2. Notably, many of these transcription factors are also hyperactivated in human tumors. Bioinformatics analysis predicted that these factors directly regulate the majority of the tumor specific gene expression, that they are interconnected by extensive cross-regulation, and that they show a high degree of co-regulation of target genes. Indeed, the factors of this network were required in multiple epithelia for tumor growth and invasiveness and knock-down of individual factors caused a reversion of the tumor specific expression profile, but had no observable effect on normal tissues. We further found that the Hippo pathway effector Yki/Sd was strongly activated in tumor cells and initiated cellular reprogramming by activating several transcription factors of this network. Thus, modeling regulatory networks identified an ectopic yet highly ordered network of master regulators that control tumor cell specific gene expression. RNA-seq gene expression profiling across Drosophila 3rd instar larval wild type wing discs and genetic perturbations of wts.

2016-06-10 | E-GEOD-71353 | biostudies-arrayexpress

An ectopic network of transcription factors regulated by Hippo signaling drives growth and invasion of a malignant tumor model [larval imaginal discs]

2016-06-10 | GSE71350 | GEO

An ectopic network of transcription factors regulated by Hippo signaling drives growth and invasion of a malignant tumor model [larval wild type discs]

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An ectopic network of transcription factors regulated by Hippo signaling drives growth and invasion of a malignant tumor model [larval imaginal discs (eye, wing and leg)]

Project description:Cancer cells have abnormal gene expression patterns, however, the transcription factors and the architecture of the regulatory network that drive cancer specific gene expression profiles is often not known. Here we studied a model of Ras-driven invasive tumorigenesis in Drosophila larval epithelial tissues and combined in vivo genetic analyses with high-throughput sequencing and computational modeling to decipher the regulatory logic of tumor cells. Surprisingly, we discovered that tumor specific gene expression is driven by a highly interconnected network composed of few transcription factors. These are: Stat, Mef2, the AP-4 homolog Cropped, the nuclear receptor Ftz-f1, the bHLH factors Myc and Taiman, and the AP-1 transcription factors Kayak, ATF-3, Pdp1, and dCEBPG. Many of these transcription factors are ectopically expressed and/or hyperactivated in human tumors. The members of this tumor master regulatory network are predicted to directly regulate the majority of the tumor specific gene expression profile. Similar to networks of master regulators that control organ development and cellular differentiation, there is a predicted high degree of co-regulation of target genes, and these network members are required in multiple eptihelia for tumor growth and invasiveness. We further found that Yki/Sd and bZIP/AP-1 factors, the downstream transcription factors of the Hippo and JNK pathways, initiate cellular reprogramming by activating several transcription factors of this network. Thus, modeling regulatory networks identified an ectopic yet highly ordered network of master regulators that control cancer cell specific gene expression. RNA-seq gene expression profiling across Drosophila 3rd instar larval imaginal discs (eye-antenna, wing and leg) in a hh driven tumor model, perturbations and controls.

2016-06-10 | E-GEOD-81272 | biostudies-arrayexpress

An ectopic network of transcription factors regulated by Hippo signaling drives growth and invasion of a malignant tumor model [larval imaginal discs (eye, wing and leg)]

2016-06-10 | GSE81272 | GEO

An ectopic network of transcription factors regulated by Hippo signaling drives growth and invasion of a malignant tumor model

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2016-06-10 | E-GEOD-71354 | biostudies-arrayexpress

Hippo signaling instructs ectopic but not normal organ growth

Project description:Hippo signaling instructs ectopic but not normal organ growth

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An ectopic network of transcription factors regulated by Hippo signaling drives growth and invasion of a malignant tumor model

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

2016-06-10 | GSE71354 | GEO