Impact of SPOP mutations on gene expression in prostate cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE338465 | GEO | 2026/07/16
REPOSITORIES: GEO
Similar Datasets
Project description:SPOP is a ubiquitin ligase adaptor frequently mutated in prostate cancer. It is involved in ubiquitination and degradation of substrate proteins. We examined the impact of wild-type and mutant SPOP on the transcriptional profile of prostate cancer cells. We cloned several naturally occurring (in human prostate cancer) SPOP mutants and expressed the corresponding constructs in prostate cancer cells. Our experimental conditions were: Human prostate cancer cells (LNCaP-Abl), transfected with control vector, SPOP-wt, and any of the following mutants: SPOP-F102C, SPOP-F133V, SPOP-F133L (2-4 biological replicates each). We analyzed their gene expression profiles for differences induced by SPOP-wt vs SPOP-mutant.
2014-10-10 | E-GEOD-59432 | biostudies-arrayexpress
Project description:Recurrent point mutations in SPOP define a distinct molecular subclass of prostate cancer. Here, we describe the first mouse model showing that mutant SPOP drives prostate tumorigenesis in vivo. Conditional expression of mutant SPOP in the prostate dramatically altered phenotypes in the setting of Pten loss, with early neoplastic lesions (high-grade prostatic intraepithelial neoplasia) with striking nuclear atypia, and invasive poorly differentiated carcinoma. In mouse prostate organoids, mutant SPOP drove increased proliferation and a transcriptional signature consistent with human prostate cancer. Using these models and human prostate cancer samples, we show that SPOP mutation activates both PI3K/mTOR and androgen receptor (AR) signaling, effectively uncoupling the normal negative feedback between these two pathways. Associated RNA-seq data deposited in GEO: GSE94839.
2017-03-20 | PXD005309 | Pride
Project description:SPOP is a ubiquitin ligase adaptor frequently mutated in prostate cancer. It is involved in ubiquitination and degradation of substrate proteins. We examined the impact of wild-type and mutant SPOP on the transcriptional profile of prostate cancer cells.
2014-10-10 | GSE59432 | GEO
Project description:Bromodomain and extraterminal domain (BET) protein inhibitors are emerging as promising therapeutics of cancers including prostate cancer. The E3 ubiquitin ligase adaptor protein speckle-type POZ protein (SPOP) is implicated in human prostate cancers due to its frequent mutation. Here we demonstrate that SPOP binds to the BET proteins BRD2, BRD3 and BRD4. Wild-type SPOP, but not prostate cancer-associated mutants, promotes polyubiquitination and proteasome degradation of BET proteins by recognizing a common degron motif. BET protein levels are highly elevated in SPOP-mutated prostate cancers in patients. Expression of cancer-derived SPOP mutants upregulates cholesterol biosynthesis genes and confers resistance to the BET inhibitor in cultured prostate cancer cells and tumors in mice, and this effect can be overcome by the AKT inhibitor. Our findings reveal BET proteins as proteolytic targets of SPOP and identify deregulated cholesterol biosynthesis as a downstream event of SPOP mutation-mediated tumorigenesis and therapy resistance in prostate cancer.
2017-07-24 | GSE88871 | GEO
Project description:Bromodomain and extraterminal domain (BET) protein inhibitors are emerging as promising therapeutics of cancers including prostate cancer. The E3 ubiquitin ligase adaptor protein speckle-type POZ protein (SPOP) is implicated in human prostate cancers due to its frequent mutation. Here we demonstrate that SPOP binds to the BET proteins BRD2, BRD3 and BRD4. Wild-type SPOP, but not prostate cancer-associated mutants, promotes polyubiquitination and proteasome degradation of BET proteins by recognizing a common degron motif. BET protein levels are highly elevated in SPOP-mutated prostate cancers in patients. Expression of cancer-derived SPOP mutants upregulates cholesterol biosynthesis genes and confers resistance to the BET inhibitor in cultured prostate cancer cells and tumors in mice, and this effect can be overcome by the AKT inhibitor. Our findings reveal BET proteins as proteolytic targets of SPOP and identify deregulated cholesterol biosynthesis as a downstream event of SPOP mutation-mediated tumorigenesis and therapy resistance in prostate cancer.
2017-07-24 | GSE78213 | GEO
Project description:Bromodomain and extraterminal domain (BET) protein inhibitors are emerging as promising therapeutics of cancers including prostate cancer. The E3 ubiquitin ligase adaptor protein speckle-type POZ protein (SPOP) is implicated in human prostate cancers due to its frequent mutation. Here we demonstrate that SPOP binds to the BET proteins BRD2, BRD3 and BRD4. Wild-type SPOP, but not prostate cancer-associated mutants, promotes polyubiquitination and proteasome degradation of BET proteins by recognizing a common degron motif. BET protein levels are highly elevated in SPOP-mutated prostate cancers in patients. Expression of cancer-derived SPOP mutants upregulates cholesterol biosynthesis genes and confers resistance to the BET inhibitor in cultured prostate cancer cells and tumors in mice, and this effect can be overcome by the AKT inhibitor. Our findings reveal BET proteins as proteolytic targets of SPOP and identify deregulated cholesterol biosynthesis as a downstream event of SPOP mutation-mediated tumorigenesis and therapy resistance in prostate cancer.
2018-03-08 | GSE98010 | GEO
Project description:Abnormal DNA methylation is one of the major factors driving oncogenesis and therapy resistance in cancer. The CULLIN3-RBX1 E3 ubiquitin ligase adaptor gene SPOP is the most frequently mutated gene in primary prostate cancers (PCa). SPOP-mutated prostate tumors strikingly associate with strongly elevated levels of genome-wide DNA hypermethylation, although the underlying mechanism remains elusive. We use reduced representation bisulfite sequencing (RRBS) to depict DNA methylation in control and SPOP F133V stably expressed 22Rv1 cells. Genomic DNA of cells are extracted and treated with restriction enzyme and followed by bisulfite sequencing to enrich for areas of the genome with a high CpG content. We find that SPOP mutant expression increases not only the overall cellular level of DNA methylation, but also specifically at loci of a subset of tumor suppressor genes (TSG) including FOXO3 and NDRG1, and this effect is mediated by GLP/G9a binding with DNMT proteins. These findings reveal a previously uncharacterized mechanism by which SPOP mutations promote DNA hypermethylation through stabilization GLP as a chromatin recruiter of DNMT. Our results also suggest that targeting DNA hypermethylation is a viable strategy for effective management of SPOP mutated PCa.
2021-08-01 | GSE155491 | GEO
Project description:Abnormal DNA methylation is one of the major factors driving oncogenesis and therapy resistance in cancer. The CULLIN3-RBX1 E3 ubiquitin ligase adaptor gene SPOP is the most frequently mutated gene in primary prostate cancers (PCa). SPOP-mutated prostate tumors strikingly associate with strongly elevated levels of genome-wide DNA hypermethylation, although the underlying mechanism remains elusive.We use Illumina Infinium MethylationEPIC BeadChip to depict DNA methylation in control and SPOP F102C stabily expressed 22Rv1 cells. Genomic DNA of cells are extracted and quantified by PicoGreen, followed by Illumina Infinium arrays. We find that SPOP mutant expression increases not only the overall cellular level of DNA methylation, but also specifically at loci of a subset of tumor suppressor genes (TSG) including FOXO3 and NDRG1, and this effect is mediated by GLP/G9a binding with DNMT proteins.These findings reveal a previously uncharacterized mechanism by which SPOP mutations promote DNA hypermethylation through stabilization GLP as a chromatin recruiter of DNMT. Our results also suggest that targeting DNA hypermethylation is a viable strategy for effective management of SPOP mutated PCa.
2021-08-01 | GSE179234 | GEO
Project description:We aimed at analyzing the transcriptome changes associated with SPOP mutation in DU145 cells
2020-07-15 | GSE147090 | GEO
Project description:Purpose: Little is known about the interplay of driver mutations that never co-occur within the same cancer cells. The latter scenario has been identified in prostate cancer where recurrent gene fusions involving the oncogenic ERG transcription factor and point mutations in the ubiquitin ligase adaptor SPOP are strictly mutually exclusive. We show that ERG and mutant SPOP – even though oncogenic on their own – are together synthetic sick. Description: RNA-Seq of lentiviral-transduced VCaP cells with stable knockdown of wild type SPOP (2 x hairpins) or stable overexpression of either wild-type or mutant SPOP (Y87C, F102C, W131G).
2020-12-05 | E-MTAB-7165 | biostudies-arrayexpress