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Homo sapiens

ABSTRACT: Endogenous Androgen Receptor proteomic profiling reveals genomic subcomplex involved in prostate tumorigenesis

OTHER RELATED OMICS DATASETS IN: PXD008056

PROVIDER: PRJNA371800 | ENA |

REPOSITORIES: ENA

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Endogenous androgen receptor proteomic profiling reveals genomic subcomplex involved in prostate tumorigenesis

Project description:Androgen receptor (AR) is a key player in prostate cancer development and progression. Here we applied immunoprecipitation mass spectrometry of endogenous AR in LNCaP cells to identify components of the AR transcriptional complex. In total, 66 known and novel AR interactors were identified in the presence of synthetic androgen, most of which were critical for AR-driven prostate cancer cell proliferation. A subset of AR interactors required for LNCaP proliferation were profiled using chromatin immunoprecipitation assays followed by sequencing, identifying distinct genomic subcomplexes of AR interaction partners. Interestingly, three major subgroups of genomic subcomplexes were identified, where selective gain of function for AR genomic action in tumorigenesis was found, dictated by FOXA1 and HOXB13. In summary, by combining proteomic and genomic approaches we reveal subclasses of AR transcriptional complexes, differentiating normal AR behavior from the oncogenic state. In this process, the expression of AR interactors has key roles by reprogramming the AR cistrome and interactome in a genomic location-specific manner.

2017-10-27 | PXD008056 | Pride

Androgen Receptor Activity is Regulated Through the Mobilization of Cell Surface Receptor Networks

Project description:The aberrant expression of androgen receptor (AR)-dependent transcriptional programs is a defining pathology of the development and progression of prostate cancers. Transcriptional cofactors that bind AR are critical determinants of prostate tumorigenesis. To gain a deeper understanding of the proteins linked to AR-dependent gene transcription, we performed a DNAaffinity chromatography-based proteomic screen designed to identify proteins involved in ARmediated gene transcription in prostate tumor cells.

2015-09-03 | PXD002596 | Pride

Montagud2022 - Prostate cancer Boolean model

Project description:Prostate cancer is the second most occurring cancer in men worldwide, and with the advances made with screening for prostate-specific antigen, it has been prone to early diagnosis and over-treatment. To better understand the mechanisms of tumorigenesis and possible treatment responses, we developed a mathematical model of prostate cancer which considers the major signalling pathways known to be deregulated. The model includes pathways such as androgen receptor, MAPK, Wnt, NFkB, PI3K/AKT, MAPK, mTOR, SHH, the cell cycle, the epithelial-mesenchymal transition (EMT), apoptosis and DNA damage pathways. The final model accounts for 133 nodes and 449 edges. We applied a methodology to personalise this Boolean model to molecular data to reflect the heterogeneity and specific response to perturbations of cancer patients, using TCGA and GDSC datasets.

2022-06-22 | MODEL2106070001 | BioModels

Endogenous Androgen Receptor proteomic profiling reveals genomic subcomplex involved in prostate tumorigenesis

Project description:Androgen Receptor (AR) is a key player in prostate cancer development and progression. Here, we applied immunoprecipitation mass spectrometry of endogenous AR in LNCaP cells to identify individual components of the AR transcription complex. In total, 66 known and novel AR interactors were identified in the presence of R1881, which were critically and selectively required in AR-driven prostate cancer cell proliferation. AR interactors required for LNCaP proliferation were profiled using ChIP-seq, identifying distinct genomic subcomplexes of AR interaction partners. Interestingly, three major subgroups of genomic subcomplexes were identified, where a selective gain-of-function for AR was identified in tumorigenesis, dictated by FOXA1 and HOXB13. Jointly, our study reveals subclasses of the AR transcription complex formation and composition, that is dictated by overexpression of AR-interactors, resulting in reprogramming of the AR cistrome and interactome in a genomic location-specific manner.

2017-09-05 | GSE94682 | GEO

Regulation of androgen receptor transcriptional activity and specificity by RNF6

Project description:The androgen receptor (AR) plays a critical role in prostate cancer. We identified an ubiquitin E3 ligase RNF6 as one of AR-associated proteins in a proteomic screening. RNF6 induces AR ubiquitination and promotes AR transcriptional activity. Specific knockdown of the endogenous RNF6 alters expression of a subset of AR target genes and diminishes recruitment of AR and its coactivators to androgen responsive elements (AREs) present in the regulatory region of these genes. Furthermore, RNF6 is overexpressed in human hormone-refractory prostate cancer tissues and required for prostate cancer cell growth under androgen-depleted conditions. Our work has provided a novel mechanism by which AR transcriptional activity and specificity is regulated, and identified RNF6 as a potential new target for prostate cancer treatment.

2009-04-06 | GSE14575 | GEO

Ornithine decarboxylase is sufficient for prostate tumorigenesis via androgen receptor signaling

Project description:Ornithine decarboxylase is sufficient for prostate tumorigenesis via androgen receptor signaling

2016-06-03 | GSE82179 | GEO

Androgen receptor programming in human tissue implicates HOXB13 in prostate pathogenesis [RNA-Seq]

Project description:The androgen receptor (AR), a nuclear transcription factor (TF), is consistently reprogrammed during prostate tumorigenesis

2015-10-12 | GSE70078 | GEO

Androgen receptor programming in human tissue implicates HOXB13 in prostate pathogenesis [ChIP-Seq]

Project description:The androgen receptor (AR), a nuclear transcription factor (TF), is consistently reprogrammed during prostate tumorigenesis

2015-10-12 | GSE56288 | GEO

Single-minded homolog 2 resides in the chromatin protein network of androgen receptor and modulates gene expression in prostate cancer cells Single-minded homolog 2 resides in the chromatin protein network of androgen receptor and modulates gene expression in prostate cancer cells

Project description:We investigated the composition of chromatin protein network around endogenous androgen receptor (AR) in VCaP castration resistant prostate cancer cells using recently developed chromatin-directed proteomic approach called ChIP-SICAP . The androgen-induced AR chromatin protein network contained expected TFs, e.g. HOXB13, chromatin remodeling proteins, e.g. SMARCA4, and several novel candidates not previously associated with AR, e.g. prostate cancer biomarker SIM2. Based on these findings, the role of SMARCA4 and SIM2 was further characterized at AR chromatin domains . Silencing of SIM2 altered chromatin accessibility at a similar number of AR-binding sites as SMARCA4, an established ATPase subunit of the BAF chromatin remodeling complex, often aberrantly expressed in prostate cancer. Despite the wide co-occurrence on chromatin of SMARCA4 and AR, depletion of SMARCA4 influenced chromatin accessibility and expression of a restricted set of AR target genes, in particular those involved in cell morphogenetic changes in epithelial-mesenchymal transition. Silencing of SIM2, in turn, affected the expression of a much larger group of androgen-regulated genes, e.g. those involved in cellular responses to external stimuli and steroid hormone stimulus. The silencing also reduced proliferation of VCaP cells and tumor size in chick embryo chorioallantoic membrane assay, further suggesting the importance of SIM2 in the regulation prostate cancer cells.

2021-06-17 | PXD025193 | Pride

ETV1 and ERG genome binding/occupancy profiling by genome tiling array

Project description:Chromosomal rearrangements involving ETS factors, ERG and ETV1, occur frequently in prostate cancer. How these factors contribute to tumorigenesis and whether they play similar in vivo roles remain elusive. We show that ERG and ETV1 control a common transcriptional network but in an opposing fashion. In mice with ERG or ETV1 targeted to the endogenous Tmprss2 locus, either factors cooperated with Pten-loss, leading to localized cancer, but only ETV1 supported development of advanced adenocarcinoma, likely through enhancement of androgen receptor signaling and steroid biosynthesis. Indeed, ETV1 expression promotes autonomous testosterone production, which may contribute to tumor progression to castration-resistant prostate cancer. Patient data confirmed association of ETV1 expression with aggressive disease. We conclude that despite many shared targets, ERG and ETV1 contribute differently to prostate tumor biology. Hence, prostate cancers with these fusions should be considered as distinct subtypes for patient stratification and therapy. Genomic targets of ERG and ETV1 transcription factors were identified by antibody-mediated and biotin-mediated ChIP-chip in human VCaP and LNCaP cells, respectively.

2013-03-01 | E-GEOD-39357 | biostudies-arrayexpress

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