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Lysine-specific demethylase 1 metastasis of androgen-independent PCa cells

ABSTRACT: Lysine-specific demethylase 1 metastasis of androgen-independent PCa cells

PROVIDER: PRJNA245395 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR1262523.fastq.gz	Fastqsanger.gz
	SRR1262524.fastq.gz	Fastqsanger.gz
	SRR1262525_1.fastq.gz	Fastqsanger.gz
	SRR1262525_2.fastq.gz	Fastqsanger.gz
	SRR1262526_1.fastq.gz	Fastqsanger.gz

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Lysine-specific demethylase 1 metastasis of androgen-independent PCa cells [RNA-seq]

Project description:The aim of this study is to identify the LSD1 target genes in metastatic androgen independent prostate cancer Lysine-specific demethylase 1 (LSD1) was shown to control gene expression and cell proliferation of androgen-dependent prostate cancer (PCa) cells, whereas the role of LSD1 in androgen-independent metastatic prostate cancer remains elusive. Here, we show that depletion of LSD1 leads to increased migration and invasion of androgen-independent PCa cells. Transcriptome and cistrome analyses reveal that LSD1 regulates expression of lysophosphatidic acid receptor 6 (LPAR6) and cytoskeletal genes including the focal adhesion adaptor protein paxillin (PXN). Enhanced LPAR6 signalling upon LSD1 depletion promotes migration with concomitant phosphorylation of PXN. In mice LPAR6 overexpression enhances, whereas knockdown of LPAR6 abolishes metastasis of androgen-independent PCa cells. Taken together, we uncover a novel mechanism of how LSD1 controls metastasis and identify LPAR6 as a promising therapeutic target to treat metastatic prostate cancer.

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Lysine-specific demethylase 1 metastasis of androgen-independent PCa cells [ChIP-seq]

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Lysine-specific demethylase 1 metastasis of androgen-independent PCa cells

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

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Lysine-Specific Demethylase 1 Has Dual Functions as a Major Regulator of Androgen Receptor Transcriptional Activity

Project description:Lysine Specific Demethylase 1 (LSD1, KDM1A) functions as a transcriptional corepressor through demethylation of histone 3 lysine 4 (H3K4), but has coactivator function on some genes through unclear mechanisms. We show that LSD1, interacting with CoREST, associates with and coactivates androgen receptor (AR) on a large fraction of androgen-stimulated genes. A subset of these AR/LSD1-associated enhancer sites have histone 3 threonine 6 phosphorylation (H3T6ph), and these sites are further enriched for androgen-stimulated genes. Significantly, despite its coactivator activity, LSD1 still mediates H3K4me2 demethylation at these androgen-stimulated enhancers. FOXA1 is also associated with LSD1 at AR regulated enhancer sites, and a FOXA1 interaction with LSD1 enhances binding of both proteins at these sites. These findings show LSD1 functions broadly as a regulator of AR function, that it maintains a transcriptional repression function at AR-regulated enhancers through H3K4 demethylation, and has a distinct AR-linked coactivator function mediated by demethylation of other substrates. Determine the role of LSD1 in androgen signaling.

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Lysine-Specific Demethylase 1 Has Dual Functions as a Major Regulator of Androgen Receptor Transcriptional Activity

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Project description:The KDM5B lysine demethylase regulates androgen receptor function and expression in prostate cancer cells

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