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Activation of AKT induces EZH2-mediated β-catenin trimethylation in colorectal cancer. [ChIP-Seq]

ABSTRACT: Activation of AKT induces EZH2-mediated β-catenin trimethylation in colorectal cancer. [ChIP-Seq]

PROVIDER: PRJNA940740 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23696615.fastq.gz	Fastqsanger.gz
	SRR23696615_1.fastq.gz	Fastqsanger.gz
	SRR23696615_2.fastq.gz	Fastqsanger.gz
	SRR23696616.fastq.gz	Fastqsanger.gz
	SRR23696616_1.fastq.gz	Fastqsanger.gz

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Activation of AKT induces EZH2-mediated β-catenin trimethylation in colorectal cancer. [RNA-Seq]

Project description:The lysine methyltransferase EZH2 is overexpressed in colorectal cancer (CRC) and has been found to be positively and negatively correlated with CRC patient survival depending on the study suggesting that EZH2 has a complex role in CRC. Here, we demonstrate that AKT-mediated EZH2 S21 phosphorylation induced EZH2 to trimethylate β-catenin at K49, which increased β-catenin’s binding to the chromatin. Additionally, EZH2-mediated β-catenin trimethylation induced β-catenin’s interaction with TCF1 and RNA polymerase II and resulted in a dramatic gain in genomic regions with β-catenin occupancy. Interestingly, EZH2 catalytic inhibition decreased stemness but increased migratory phenotypes of CRC cells with active AKT. Overall, we demonstrated that EZH2 modulates AKT-induced changes in gene expression through the AKT/EZH2/β-catenin axis in CRC. Our results suggest that EZH2 inhibitors have tumor-inhibiting and promoting effects in CRC as they inhibit EZH2-mediated methylation of histone and non-histone targets like β-catenin.

2023-08-23 | GSE226584 | GEO

Activation of AKT induces EZH2-mediated β-catenin trimethylation in colorectal cancer. [Cut & Run]

2023-08-23 | GSE226588 | GEO

Activation of AKT induces EZH2-mediated β-catenin trimethylation in colorectal cancer. [ChIP-Seq]

2023-08-23 | GSE226587 | GEO

Activation of AKT induces EZH2-mediated β-catenin trimethylation in colorectal cancer.

Project description:Activation of AKT induces EZH2-mediated β-catenin trimethylation in colorectal cancer.

| PRJNA940741 | ENA

Activation of AKT induces EZH2-mediated β-catenin trimethylation in colorectal cancer. [Cut & Run]

Project description:Activation of AKT induces EZH2-mediated β-catenin trimethylation in colorectal cancer. [Cut & Run]

| PRJNA940747 | ENA

Activation of AKT induces EZH2-mediated β-catenin trimethylation in colorectal cancer. [RNA-Seq]

Project description:Activation of AKT induces EZH2-mediated β-catenin trimethylation in colorectal cancer. [RNA-Seq]

| PRJNA940739 | ENA

Activation of AKT induces EZH2-mediated β-catenin trimethylation in colorectal cancer.

Project description:Colorectal cancer (CRC) develops in part through the deregulation of different signaling pathways, including activation of the WNT/β-catenin and PI3K/AKT pathways. Additionally, the lysine methyltransferase enhancer of zeste homologue 2 (EZH2) is commonly overexpressed in CRC. EZH2 canonically represses gene transcription by trimethylating lysine 27 of histone H3, but also has non-histone substrates. Here, we demonstrated that in CRC, active AKT phosphorylated EZH2 on serine 21. Phosphorylation of EZH2 by AKT induced EZH2 to interact with and methylate β-catenin at lysine 49, which increased β-catenin's binding to the chromatin. Additionally, EZH2-mediated β-catenin trimethylation induced β-catenin to interact with TCF1 and RNA polymerase II and resulted in dramatic gains in genomic regions with β-catenin occupancy. EZH2 catalytic inhibition decreased stemness but increased migratory phenotypes of CRC cells with active AKT. Overall, we demonstrated that EZH2 modulates AKT-induced changes in gene expression through the AKT/EZH2/β-catenin axis in CRC.

| S-EPMC10475482 | biostudies-literature

Activation of AKT induces EZH2-mediated β-catenin trimethylation in colorectal cancer.

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-08-23 | GSE226589 | GEO

CCN6/WISP3 suppresses metaplastic breast carcinoma by antagonizing a WNT/b-catenin/EZH2 cascade [ChIP-seq]

Project description:Metaplastic breast carcinomas (mBrCAs) are a highly aggressive subtype of triple negative breast cancer (TNBC) with histological evidence of epithelial to mesenchymal transition (EMT) and aberrant differentiation, including varied non-glandular features. CCN6/WISP3 tumor suppressor gene inactivation and b-catenin-dependent Wnt pathway activation are often seen in mBrCAs. We have reported MMTV-Cre;Ccn6fl/fl (Ccn6-KO) mice develop spindle mBrCAs with EMT and elevated expression of the Wnt/b-catenin pathway genes HMGA2 and IGF2BP2. The mechanisms by which the secreted CCN6 protein exerts tumor suppressor functions in breast tissues are uncertain. Here, we show recombinant CCN6 protein interacts with Wnt receptor FZD8 and co-receptor LRP6 on mBrCA cells to antagonize Wnt ligand-mediated activation of b-catenin/T-cell-factor (TCF) transcription. We identify the gene for histone methyltransferase EZH2, the catalytic component of polycomb repressive complex 2, as a β-catenin/TCF transcriptional target in Ccn6-KO mBrCA cells. Inhibition of Wnt/β-catenin/TCF function in Ccn6-KO mBrCA cells led to reduced EZH2 levels and decreased histone H3 lysine 27 trimethylation, resulting in deregulation of specific gene targets. Pharmacological inhibition of EZH2 reduced growth and metastasis of Ccn6-KO mBrCA mammary tumors and induced an epithelial phenotype in vivo. In human breast cancer specimens, low CCN6 is significantly associated with activated β-catenin and high EZH2 in spindle mBrCAs compared to other subtypes. Collectively, our findings establish a novel tumor suppressor mechanism for CCN6 as a key negative regulator of a b-catenin/TCF-EZH2 axis and highlight how CCN6 restoration or b-catenin or EZH2 inhibition could have therapeutic relevance for patients with spindle mBrCAs.

2024-07-10 | GSE250574 | GEO

CCN6/WISP3 suppresses metaplastic breast carcinoma by antagonizing a WNT/b-catenin/EZH2 cascade [RNA-seq]

2024-07-10 | GSE250538 | GEO