Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

PLK1 Inhibitors and Abiraterone Synergistically Disrupt Mitosis and Kill Cancer Cells of Disparate Origin Independently of Androgen Receptor Signaling

ABSTRACT: PLK1 Inhibitors and Abiraterone Synergistically Disrupt Mitosis and Kill Cancer Cells of Disparate Origin Independently of Androgen Receptor Signaling

PROVIDER: PRJNA899498 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR22229700.fastq.gz	Fastqsanger.gz
	SRR22229800.fastq.gz	Fastqsanger.gz
	SRR22229900.fastq.gz	Fastqsanger.gz
	SRR22230000.fastq.gz	Fastqsanger.gz
	SRR22229701.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 348

Similar Datasets

PLK1 Inhibitors and Abiraterone Synergistically Disrupt Mitosis and Kill Cancer Cells of Disparate Origin Independently of Androgen Receptor Signaling

Project description:We found that synergy between the antiandrogen abiraterone and Plk1 inhibitors was completely independent of abiraterone's effects on AR signaling. To identify AR-independent effects of abiraterone we designed a comprehensive RNA seq experiment. This identified an AR-independent synergy-specific gene set signature that was induced by abiraterone treatment and was dominated by gene sets related to mitosis and the mitotic spindle. AR-independent effects of abiraterone were isolated by including an enzalutamide treatment arm and by utilizing cancer cell lines that do not express the AR. Synergy-specific gene expression changes were identified by using cell lines that responded synergistically or non-synergistically to combined abiraterone and onvansertib.

2023-01-24 | GSE217537 | GEO

Plk1 Inhibitors and Abiraterone Synergistically Disrupt Mitosis and Kill Cancer Cells of Disparate Origin Independently of Androgen Receptor Signaling.

Project description:Abiraterone is a standard treatment for metastatic castrate-resistant prostate cancer (mCRPC) that slows disease progression by abrogating androgen synthesis and antagonizing the androgen receptor (AR). Here we report that inhibitors of the mitotic regulator polo-like kinase-1 (Plk1), including the clinically active third-generation Plk1 inhibitor onvansertib, synergizes with abiraterone in vitro and in vivo to kill a subset of cancer cells from a wide variety of tumor types in an androgen-independent manner. Gene-expression analysis identified an AR-independent synergy-specific gene set signature upregulated upon abiraterone treatment that is dominated by pathways related to mitosis and the mitotic spindle. Abiraterone treatment alone caused defects in mitotic spindle orientation, failure of complete chromosome condensation, and improper cell division independently of its effects on AR signaling. These effects, although mild following abiraterone monotherapy, resulted in profound sensitization to the antimitotic effects of Plk1 inhibition, leading to spindle assembly checkpoint-dependent mitotic cancer cell death and entosis. In a murine patient-derived xenograft model of abiraterone-resistant metastatic castration-resistant prostate cancer (mCRPC), combined onvansertib and abiraterone resulted in enhanced mitotic arrest and dramatic inhibition of tumor cell growth compared with either agent alone. Overall, this work establishes a mechanistic basis for the phase II clinical trial (NCT03414034) testing combined onvansertib and abiraterone in mCRPC patients and indicates this combination may have broad utility for cancer treatment.SignificanceAbiraterone treatment induces mitotic defects that sensitize cancer cells to Plk1 inhibition, revealing an AR-independent mechanism for this synergistic combination that is applicable to a variety of cancer types.

| S-EPMC9852064 | biostudies-literature

The Eyes Absent family members EYA4 and EYA1 promote PLK1 activation and successful mitosis through tyrosine dephosphorylation: PLK1 PRM

Project description:The aim of these experiments was to quantify PLK1 tyrosine phosphosites with respect to EYA4 and EYA1. PRM was performed on immunopurified PLK1. This was part of a larger project to characterize the effects of EYA4 mediated dephosphorylation on PLK1 functions.

2024-02-26 | PXD037064 | Pride

Abiraterone acetate and di-n-butyl phthalate (DBP) response in a human fetal testis xenograft bioassay

Project description:The goal of this study was to determine the effects of a well-characterized anti-androgen, abiraterone acetate, and a suspected human anti-androgen, di-n-butyl phthalate (DBP) on the androgenic function of human fetal testis. Human fetal testis was xenografted into the renal subcapsular space of castrated male athymic nude mice. Hosts were treated with hCG to stimulate testosterone production in the xenografts, and were concurrently treated with either abiraterone acetate or DBP. While abiraterone acetate (14 d, 75 mg/kg/d p.o.) dramatically reduced testosterone and the weights of androgen-sensitive host organs, DBP (14 d, 500 mg/kg/d p.o.) had no effect on androgenic endpoints. Three paired analyses were performed using the LIMMA package in R (commands lmfit and eBayes), with the Benjamini-Hochberg correction for multiple comparisons (Smyth 2005): vehicle-treated xenografts vs. unimplanted testis (n=5), abiraterone-treated xenografts vs. matched control xenografts (n=3), and DBP-treated xenografts vs. matched control xenografts (n=3). There were significant differences in gene expression between grafted and ungrafted samples, including dramatic upregulation of microRNAs. Gene expression analysis also showed that abiraterone decreased expression of genes related to cell differentiation, while DBP induced expression of oxidative stress response genes and decreased expression of factors related to embryonic development. 17 xenograft samples were analyzed, including 5 unimplanted samples, 6 vehicle treated xenografts, 3 abiraterone acetate-treated xenografts, and 3 DBP-treated xenografts. Samples were paired (derived from the same donor tissue) for each comparison: vehicle vs. unimplanted (n=5), abiraterone vs. vehicle (n=3), and DBP vs. vehicle (n=3).

2013-10-31 | E-GEOD-49244 | biostudies-arrayexpress

Expression profile in Plk1(+/-) aortas

Project description:Transcriptional profiling of mouse aortas comparing control wild-type animals with aortas from three different Plk1(+/-) mice. Goal was to determine the effects of Plk1 haploinsufficiency in aorta expression profiles.

2017-07-01 | GSE85199 | GEO

Genetic enhancers of partial PLK1 inhibition reveal hypersensitivity to kinetochore perturbations

Project description:Polo-like kinase 1 (PLK1) is a serine/threonine kinase required for mitosis and cytokinesis. As cancer cells are often hypersensitive to partial PLK1 inactivation, chemical inhibitors of PLK1 have been developed and tested in clinical trials. However, these molecules alone were not completely effective. PLK1 promotes numerous molecular and cellular events in the cell division cycle. To date, it is unclear which of these events most crucially depend on PLK1 activity. We used a CRISPR-based genome-wide screening strategy to identify genes whose inactivation enhances cell proliferation defects upon partial chemical inhibition of PLK1. Genes identified encode proteins that are functionally linked to PLK1 in multiple ways. Among them, factors that promote centromere and kinetochore function were clearly enriched. In particular, inactivation of the kinesin KIF18A or SKA1 in PLK1-compromised cells results in mitotic defects, activation of the spindle assembly checkpoint and nuclear reassembly defects. Our results suggest that functions of PLK1 at kinetochores are most sensitive to its inhibition, and point at KIF18A as a possible target for combinatorial therapies using existing PLK1 inhibitors.

2023-10-02 | GSE228155 | GEO

PLK1 signaling coopereates with estrogen receptor-dependent gene transcription.

Project description:Analysis of MCF7 breast cancer cells treated with estadiol for 6 h in presence or absence of the specific PLK1 inhibitor BI2536. Together with CHIP and global phosphoproteome data, the results demonstrate a key role of PLK1 in the estrogen receptor-mediated gene response. Hormone-deprived MCF7 cells were pretreated with BI2536 or vehicle (DMSO) followed by induction with estradiol (E2) or vehicle (ethanol). RNA of each condition was analysed in triplicate on an Agilent Human genome 4x44k v2 microarray [note: MCF7_DMSO_E2_rep3 sample was a clear technical outlier (poor hybridization), and was therefore excluded from the further analysis/this record].

2014-01-01 | E-GEOD-46856 | biostudies-arrayexpress

Abiraterone resistance in prostate cancer cells

Project description:Abiraterone resistance in prostate cancer cells

| PRJNA909815 | ENA

Epigenome analysis of normal and PLK1 knockdown samples

Project description:The Illumina Infinium 850k Human DNA methylation Beadchip was used to obtain DNA methylation profiles in normal and PLK1 knockdown DU145 cell samples. Samples included normal and PLK1 knockdown DU145 cell samples, Each sample is repeated three times.

2022-02-22 | GSE167261 | GEO

Abiraterone resistance in prostate cancer cells

Project description:Castration resistant prostate cancer (CRPC) develops resistance to antiandrogens affecting Androgen Receptor (AR) signaling through a variety of mechanism. Because of this, the efficacy of androgen receptor targeted therapy remains limited for many patients with CRPC. We developed C42B-Abiraterone (Abi) and resistance cells to study changes in transcriptomic profile compared to parental cells.

2023-01-01 | GSE220467 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data