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Androgen receptor functions as transcriptional repressor of Cancer Associated Fibroblast (CAF) activation

ABSTRACT: Androgen receptor functions as transcriptional repressor of Cancer Associated Fibroblast (CAF) activation

PROVIDER: PRJNA419756 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6321990.fastq.gz	Fastqsanger.gz
	SRR6321971.fastq.gz	Fastqsanger.gz
	SRR6321972.fastq.gz	Fastqsanger.gz
	SRR6321985.fastq.gz	Fastqsanger.gz
	SRR6321986.fastq.gz	Fastqsanger.gz

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Androgen receptor functions as transcriptional repressor of Cancer Associated Fibroblast (CAF) activation [RNA-seq]

Project description:Androgen receptor functions as transcriptional repressor of Cancer Associated Fibroblast (CAF) activation [RNA-seq]

| PRJNA419758 | ENA

Androgen receptor functions as transcriptional repressor of Cancer Associated Fibroblast (CAF) activation [ChIP-seq]

Project description:Androgen receptor functions as transcriptional repressor of Cancer Associated Fibroblast (CAF) activation [ChIP-seq]

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Androgen receptor functions as transcriptional repressor of Cancer Associated Fibroblast (CAF) activation [ChIP-seq]

Project description:The age-associated increase of cancer risk has been linked with stromal fibroblast senescence and early steps of Cancer Associated Fibroblast (CAF) activation. Surprisingly little is known about the role of androgen receptor (AR) signalling in this context. We show that AR expression is down-modulated in stromal fibroblasts underlying premalignant skin cancer lesions (actinic keratoses, AK) as well as in CAFs from the three major skin cancer types, squamous (SCC) and basal cell (BCC) carcinomas and melanomas. Decreased AR expression is linked to the concomitant down-modulation of CSL, key effector of canonical Notch signalling and global modulator of chromatin configuration, and it can be counteracted by treatment with BET inhibitors, which reverse CAF activation. Functionally, AR gene silencing in dermal fibroblasts results in p53-dependent senescence and induction of key CAF-effector genes, with AR physically converging with CSL in negative control of these genes. The findings are of functional significance as, in an orthotopic model of skin cancer, dermal fibroblasts with AR loss enhance significantly tumorigenicity of SCC and melanoma cells. As such, the findings establish AR as a novel potential target for stroma-focused cancer prevention and treatment.

2018-08-28 | GSE107320 | GEO

Androgen receptor functions as transcriptional repressor of Cancer Associated Fibroblast (CAF) activation [RNA-seq]

2018-08-28 | GSE107319 | GEO

Androgen receptor functions as transcriptional repressor of Cancer Associated Fibroblast (CAF) activation

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

2018-08-28 | GSE107321 | GEO

Genome-wide DNA methylation status of scirrhous CAF, non-scirrhous CAF, and GIST fibroblast

Project description:Genome-wide DNA methylation status of scirrhous CAF, non-scirrhous CAF, and GIST fibroblast

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Androgen receptor functions as transcriptional repressor of cancer-associated fibroblast activation.

Project description:The aging-associated increase of cancer risk is linked with stromal fibroblast senescence and concomitant cancer-associated fibroblast (CAF) activation. Surprisingly little is known about the role of androgen receptor (AR) signaling in this context. We have found downmodulated AR expression in dermal fibroblasts underlying premalignant skin cancer lesions (actinic keratoses and dysplastic nevi) as well as in CAFs from the 3 major skin cancer types, squamous cell carcinomas (SCCs), basal cell carcinomas, and melanomas. Functionally, decreased AR expression in primary human dermal fibroblasts (HDFs) from multiple individuals induced early steps of CAF activation, and in an orthotopic skin cancer model, AR loss in HDFs enhanced tumorigenicity of SCC and melanoma cells. Forming a complex, AR converged with CSL/RBP-Jκ in transcriptional repression of key CAF effector genes. AR and CSL were positive determinants of each other's expression, with BET inhibitors, which counteract the effects of decreased CSL, restoring AR expression and activity in CAFs. Increased AR expression in these cells overcame the consequences of CSL loss and was by itself sufficient to block the growth and tumor-enhancing effects of CAFs on neighboring cancer cells. As such, the findings establish AR as a target for stroma-focused cancer chemoprevention and treatment.

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Gene Expression Analysis of Cancer-Associated Fibroblast (CAF) compared to Normal Fibroblast (NF)

Project description:Gene Expression Analysis of Cancer-Associated Fibroblast (CAF) compared to Normal Fibroblast (NF)

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Proximity labeling proteomics of the androgen receptor reveals Kruppel-Like Factor 4 as a repressor of androgen-dependent genes

Project description:Prostate cancer (PCa) is the most frequently diagnosed cancer in Canadian men and is the third cause of cancer mortality. PCa initiation and growth is driven by the androgen receptor (AR). AR is activated by androgens such as testosterone and controls prostatic cell proliferation and survival. We sought to characterize global AR signalling networks. We performed BioID proximity labeling proteomics in androgen-dependent LAPC4 cells to delineate AR protein interaction networks. We report the identification of 32 AR associated proteins in non-stimulated cells. Strikingly, the AR signalling network increased to 183 and 201 proteins, upon 24h or 72h androgenic stimulation, respectively. Among this group, we identified 215 proteins that were not previously reported as AR interactors. Interestingly, these AR associated proteins were previously reported to be involved in DNA metabolism, RNA processing and RNA polymerase II transcription. Moreover, we identified 44 transcription factors, such as the Krüppel-like factor 4 (KLF4), which was specifically revealed in androgen-stimulated cells. We determined that KLF4 acts as a repressor of AR target genes transcription in PCa cells. Taken together, our data report the largest high-confidence proximity networks for AR in PCa cells.

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Gene Expression Analysis of Cancer-Associated Fibroblast (CAF) compared to Normal Fibroblast (NF) [microarray]

Project description:Analysis of differentially expressed genes in CAF associated with PDAC vs NF Total RNA obtained from PDAC CAF and NF samples

2014-06-18 | E-GEOD-53524 | biostudies-arrayexpress