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KDM4 inhibition targets breast cancer stem cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE95294 | GEO | 2017/12/15

SECONDARY ACCESSION(S): PRJNA376573

REPOSITORIES: GEO

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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

Identification of miRNA targets in breast cancer cells

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-10-21 | E-GEOD-48162 | biostudies-arrayexpress

KDM4 inhibition targets breast cancer stem cells

Project description:KDM4 inhibition targets breast cancer stem cells

| PRJNA376573 | ENA

Targeted inhibition of three human breast cancer cell lines as model systems of ERBB2-positive breast cancer

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-08-22 | E-GEOD-50109 | biostudies-arrayexpress

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

Comprehensive genomic analysis identify novel subtypes and targets of triple-negative breast cancer

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-12-23 | E-GEOD-76275 | biostudies-arrayexpress

Genomic targets, and histone acetylation and gene expression profiling of neural HDAC inhibition

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-07-09 | E-GEOD-44868 | biostudies-arrayexpress

Inhibition of neuronal nitric oxide synthase activity promotes migration of human induced pluripotent stem cell-derived neural stem cells towards cancer cells

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-02-28 | E-GEOD-40751 | biostudies-arrayexpress

CREBBP/EP300 acetyltransferase inhibition targets lineage specific enhancers to inhibit the proliferation of ER+ breast cancer cells

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

2022-03-04 | GSE190163 | GEO

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