Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Combination CDC-like kinase inhibition (CLK) and taxane therapy in CTNNB1-mutated endometrial cancer

ABSTRACT: SM08502 is a novel pan CDC-like kinase (CLK) inhibitor that targets mRNA splicing and is optimized for Wnt pathway inhibition. Previous evaluation of single agent CLK inhibition (SM04690) demonstrated inhibition of tumor progression and b-catenin/TCF transcriptional activity in CTNNB1-mutant endometrial cancer (EC). In-vitro analysis of SM08502 similarly decreases Wnt transcriptional activity and cellular proliferation while increasing cellular apoptosis. Examining transcriptomic analysis, SM08502 increases pathways involved in RNA metabolism and spliceosome. Examining alternative splicing (AS) events, SM08502 increased differential splicing compared to treatment with paclitaxel. AS regulation is an important post-transcriptional mechanism associated with the oncogenic process in many cancers, including EC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE215975 | GEO | 2023/08/07

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

S2 cells transfected with Clk

Project description:S2 cells transfected with pAc-Clk or empty vector Keywords: S2 cells Clk

2007-07-09 | GSE7653 | GEO

CLK targets from fly heads

Project description:CLK targets from fly heads using the TIM-GAL4; UAS-CLKGR line Keywords: CLK TARGETS

2007-07-09 | GSE7646 | GEO

CLK:BMAL1 is a pioneer-like transcription factor [CLK_ChIP]

Project description:The mammalian circadian clock relies on the master genes CLOCK (CLK) and BMAL1 and drives rhythmic gene expression to regulate biological functions under circadian control. We recently uncovered a surprising disconnect between the rhythmic binding of CLK:BMAL1 on DNA and the transcription of its target genes, suggesting that they are regulated by as yet uncharacterized mechanisms. Here we show that rhythmic CLK:BMAL1 DNA binding promotes rhythmic chromatin opening. The underlying mechanisms include CLK:BMAL1 binding to nucleosomes and rhythmic chromatin modifications, including the incorporation of the histone variant H2A.Z. This rhythmic chromatin remodeling mediates the rhythmic binding of other transcription factors adjacent to CLK:BMAL1, suggesting that the activity and the tissue-specific expression of these other transcription factors contribute to the genome-wide CLK:BMAL1 heterogeneous transcriptional output. These data therefore indicate that the clock regulation of transcription relies on the rhythmic regulation of chromatin accessibility and suggest that the concept of pioneer function extends to acute gene regulation, well beyond the current confines of developmental/cell specification.

2014-01-06 | GSE47144 | GEO

CLK IP-MS - CLK-dependent exon recognition and conjoined gene formation revealed with a novel small molecule inhibitor

Project description:CLK kinase was immunoprecipitated using differential tagging of the N- and C-terminus

2017-03-14 | PXD003839 | Pride

CLK:BMAL1 is a pioneer-like transcription factor [CLK_ChIP]

2014-01-06 | E-GEOD-47144 | biostudies-arrayexpress

Transcription profiling of Drosophila S2 cells transfected with Clk

Project description:S2 cells transfected with pAc-Clk or empty vector Experiment Overall Design: S2 cells transfected with pAc-Clk or empty vector. Cells were transfected and RNA collected after 48hs

2008-06-15 | E-GEOD-7653 | biostudies-arrayexpress

CLK:BMAL1 is a pioneer-like transcription factor [H2AZ-ChIP]

2014-01-06 | GSE47143 | GEO

CLK:BMAL1 is a pioneer-like transcription factor [MNase-Seq]

2014-01-06 | GSE47142 | GEO

CLK:BMAL1 is a pioneer-like transcription factor [H2AZ-ChIP]

2014-01-06 | E-GEOD-47143 | biostudies-arrayexpress

CLK:BMAL1 is a pioneer-like transcription factor [MNase-Seq]

2014-01-06 | E-GEOD-47142 | biostudies-arrayexpress