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KDM4 inhibition targets breast cancer stem cells

ABSTRACT: KDM4 inhibition targets breast cancer stem cells

PROVIDER: PRJNA376573 | ENA |

REPOSITORIES: ENA

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KDM4 inhibition targets breast cancer stem cells

Project description:Cancer progression is associated with alterations of epigenetic regulators such as histone-lysine demethylases 4 (KDM4)2-5. During breast cancer therapy, classical treatments fail to address resistant cancer stem cell populations6-10. Here, we identified a novel KDM4 inhibitor (KDM4(i)) with unique preclinical characteristics. KDM4(i) is a highly potent pan KDM4 inhibitor that specifically blocks the demethylase activity of KDM4A, B, C, and D but not that of the other members of the KDM family. We validated the KDM4(i) anti-tumoral properties under conditions recapitulating patient tumors. Therefore, we established a method to isolate and grow triple-negative breast cancer stem cells (BCSCs) from individual patient tumors after neoadjuvant chemotherapy. Limiting dilution orthotopic xenografts of these BCSCs faithfully regenerate original patient tumor histology and gene expression. KDM4(i) blocks proliferation, sphere formation and xenograft tumor growth of BCSCs. Importantly, KDM4(i) abrogates expression of EGFR, a driver of therapy-resistant triple-negative breast tumor cells11, via inhibition of the KDM4A demethylase activity. Taken together, we present a unique BCSC culture system as a basis for therapeutic compound identification and demonstrate that KDM4 inhibition is a new therapeutic strategy for the treatment of triple-negative breast cancer.

2018-04-10 | GSE95042 | GEO

KDM4 inhibition targets breast cancer stem cells [RNA-Seq]

Project description:We treated breast cancer stemm cells (BCSC) with a KDM4 inhibitor

2017-12-15 | GSE95293 | GEO

KDM4 inhibition targets breast cancer stem cells [ChIP-Seq]

Project description:We treated breast cancer stemm cells (BCSC) with a KDM4 inhibitor or performed knockdown of KDM4A

2017-12-15 | GSE95190 | GEO

Expression data from KDM4 inhibition

Project description:Expression data from KDM4 inhibition

| PRJNA665064 | ENA

KDM4 inhibition targets breast cancer stem cells

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

2017-12-15 | GSE95294 | GEO

RNA-seq using RNA from KDM4 WT and Knockout haematopoietic stem cells

Project description:The KDM4/JMJD2 are H3K9- and H3K36- specific demethylases, which are considered promising therapeutic targets for the treatment of acute myeloid leukemia (AML) harboring MLL-translocations. Here, we investigate the long-term effects of depleting KDM4 activity on normal hematopoiesis to probe potential side effects of continuous inhibition of these enzymes. Utilizing conditional Kdm4a/Kdm4b/Kdm4c triple-knockout mice we show that KDM4 activity is required for hematopoietic stem cell (HSC) maintenance in vivo. The knockout of the KDM4 demethylases leads to accumulation of H3K9me3 on transcription start sites and the corresponding downregulation of expression of several genes in hematopoietic stem cells. We show that two of these genes, Taf1b and Nom1, are essential for the maintenance of hematopoietic cells. Taken together, our results show that the KDM4 demethylases are required for the expression of genes essential for the long-term maintenance of normal hematopoiesis.

2019-04-02 | GSE129137 | GEO

Homo sapiens

Project description:KDM4 inhibition targets breast cancer stem cells

| PRJNA375805 | ENA

Homo sapiens

Project description:KDM4 inhibition targets breast cancer stem cells [ChIP-Seq]

| PRJNA376389 | ENA

Homo sapiens

Project description:KDM4 inhibition targets breast cancer stem cells [RNA-Seq]

| PRJNA376575 | ENA

Understanding the impact of KDM4 inhibition on host cell processes

Project description:HepG2-NTCP cells were cultured in 1% oxygen or treated with a KDM4 inhibitor, QC6352, for 72 hours. RNA was extracted and the impact of treatment on the cellular transcriptome was investigated by RNA-sequencing.

2024-01-31 | GSE186279 | GEO

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