NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE107320 Query DataSets for GSE107320
Status Public on Aug 28, 2018
Title Androgen receptor functions as transcriptional repressor of Cancer Associated Fibroblast (CAF) activation [ChIP-seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary 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.
 
Overall design Chip tagmentation was carried out as in (Kim et al. 2017) using endogenous AR antibody in human dermal fibroblasts (HDFs)
 
Contributor(s) Clocchiatti A, Ghosh S, Procopio M, Mazzeo L, Bordignon P, Ostano P, Goruppi S, Bottoni G, Levesque M, Dummer R, Neel V, Özdemir BC, Dotto GP
Citation(s) 30395538
Submission date Nov 24, 2017
Last update date May 15, 2019
Contact name Paola Ostano
Organization name Fondazione Edo ed Elvo Tempia
Street address via Malta 3
City Biella
ZIP/Postal code 13900
Country Italy
 
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (2)
GSM2864778 Anti-AR antibody
GSM2864779 Non-immune IgGs
This SubSeries is part of SuperSeries:
GSE107321 Androgen receptor functions as transcriptional repressor of Cancer Associated Fibroblast (CAF) activation
Relations
BioProject PRJNA419759
SRA SRP125603

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE107320_RAW.tar 425.5 Mb (http)(custom) TAR (of BIGWIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap