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A novel small molecule targeting oncogenic PELP1 demonstrates anti-tumor activity in wild type and mutant estrogen receptor alpha-positive breast cancer

ABSTRACT: A novel small molecule targeting oncogenic PELP1 demonstrates anti-tumor activity in wild type and mutant estrogen receptor alpha-positive breast cancer

PROVIDER: PRJNA818313 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18399136.fastq.gz	Fastqsanger.gz
	SRR18399137.fastq.gz	Fastqsanger.gz
	SRR18399138.fastq.gz	Fastqsanger.gz
	SRR18399139.fastq.gz	Fastqsanger.gz
	SRR18399140.fastq.gz	Fastqsanger.gz

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Similar Datasets

PELP1 ChIP-chip from MCF-7 cells

Project description:Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) is a transcriptional coactivator that has previously been shown to collaborate with nuclear receptors. Evidence from other groups suggest that PELP1 may stimulate transcription by displacing the linker histone H1 and/or by recruiting the lysine demethylase KDM1 to demethylate H3K9me2. Also known as modulator of the non-genomic activity of estrogen receptor (MNAR), PELP1 has also been implicated promoting estrogen receptor signaling from the plasma membrane. We recently identified PELP1 a factor that interacts with the macro domain of the histone variant macroH2A1. To determine if PELP1 interacts with macroH2A1 in cells, we performed PELP1 ChIP-chip from MCF-7 cells. The pattern of PELP1 bind across the genome strongly correlates with that previously determined for macroH2A1. This data combined with additional experiments allow us to conclude that macroH2A1 regulates target gene expression in part by recruiting the transcriptional coregulator PELP1. Two PELP1 ChIP-chip biological replicates from MCF-7 human breast cancer cells are included.

2014-04-24 | E-GEOD-22254 | biostudies-arrayexpress

PELP1 ChIP-chip from MCF-7 cells

2014-04-24 | GSE22254 | GEO

Progesterone receptor-B enhances estrogen responsiveness of breast cancer cells via scaffolding PELP1- and estrogen receptor-containing transcription complexes

Project description:Progesterone and estrogen are important drivers of breast cancer proliferation. Herein, we probed estrogen receptor-α (ER) and progesterone receptor (PR) cross-talk in breast cancer models. Stable expression of PR-B in PR-low/ER+ MCF7 cells increased cellular sensitivity to estradiol and insulin-like growth factor 1 (IGF1), as measured in growth assays performed in the absence of exogenous progestin; similar results were obtained in PR-null/ER+ T47D cells stably expressing PR-B. Genome-wide microarray analyses revealed that unliganded PR-B induced robust expression of a subset of estradiol-responsive ER target genes, including cathepsin-D (CTSD). Estradiol-treated MCF7 cells stably expressing PR-B exhibited enhanced ER Ser167 phosphorylation and recruitment of ER, PR and the proline-, glutamate- and leucine-rich protein 1 (PELP1) to an estrogen response element in the CTSD distal promoter; this complex co-immunoprecipitated with IGF1 receptor (IGFR1) in whole-cell lysates. Importantly, ER/PR/PELP1 complexes were also detected in human breast cancer samples. Inhibition of IGF1R or phosphoinositide 3-kinase blocked PR-B-dependent CTSD mRNA upregulation in response to estradiol. Similarly, inhibition of IGF1R or PR significantly reduced ER recruitment to the CTSD promoter. Stable knockdown of endogenous PR or onapristone treatment of multiple unmodified breast cancer cell lines blocked estradiol-mediated CTSD induction, inhibited growth in soft agar and partially restored tamoxifen sensitivity of resistant cells. Further, combination treatment of breast cancer cells with both onapristone and IGF1R tyrosine kinase inhibitor AEW541 was more effective than either agent alone. In summary, unliganded PR-B enhanced proliferative responses to estradiol and IGF1 via scaffolding of ER-α/PELP1/IGF1R-containing complexes. Our data provide a strong rationale for targeting PR in combination with ER and IGF1R in patients with luminal breast cancer.

2015-03-15 | GSE45643 | GEO

The Estrogen Receptor Co-Regulator Protein, Proline Glutamic Acid and Leucine Rich Protein 1 (PELP1) Mediates Estrogen Rapid Signaling and Neuroprotection in the Brain

Project description:We examined the role of PELP1 in E2-ER-mediated transcription in the hippocampus under conditions of GCI by perfroming global transcriptome analysis. E2-treated FLOX and PELP1 FBKO mice were subjected to GCI followed by 24 h reperfusion and the isolated RNA was utilized for RNA-seq analysis. Our results demonstrated that PELP1 is needed for optimal activation of E2-regulated genes following GCI. Total RNA was isolated from the hippocampus of ovariectomized FLOX and PELP1 FBKO mice (implanted with E2 mini pumps) that were subjected to GCI followed by 24 h reperfusion. Illumina TruSeq RNA Sample Preparation was performed following manufacturer's protocol. Samples were run on an Illumina HiSeq 2000 in duplicate. The combined raw reads were aligned to UCSC hg19 and genes were annotated by Tophat. Genes were annotated and quantified by HTSeq-DESeq pipeline.

2015-12-07 | E-GEOD-72136 | biostudies-arrayexpress

A novel small molecule targeting oncogenic PELP1 demonstrates anti-tumor activity in wild type and mutant estrogen receptor alpha-positive breast cancer

Project description:RNA-seq analyses showed SMIP34 treatment altered the expression of genes associated withEstrogen Response, Cell Cycle and Apoptosis pathways

2022-11-02 | GSE199088 | GEO

The Estrogen Receptor Co-Regulator Protein, Proline Glutamic Acid and Leucine Rich Protein 1 (PELP1) Mediates Estrogen Rapid Signaling and Neuroprotection in the Brain

2015-12-07 | GSE72136 | GEO

MCF-7 cell RNA-seq analysis of PELP1-induced gene expression

Project description:RNA-seq was performed on MCF-7 cells expressing vector control (LXSN), PELP1-wt, and PELP1-cyto

2021-07-05 | GSE126776 | GEO

The therapeutic potential and significance of the PELP1 signaling pathway in hepatocellular carcinoma

Project description:We examined the significance and therapeutic potential of targeting PELP1 in Hepatocellular carcinoma. Total RNA were isolated from HEP3B-control Sh, and HEP3B-PELP1-Sh cells using RNeasy mini kit, and total RNA was isolated for RNA-seq analysis. Our results demonstrated that PELP1 knockdown regulates pathways related to inflammation and interferon signaling and downregulates several pathways including MYC and E2F.

2024-10-16 | GSE254860 | GEO

Global genomic and proteomic analysis of TNBC cells identifies the critical role of PELP1 in ribosome biogenesis

Project description:We examined the mechanisms by which PELP1 regulates TNBC progression. MDA-MB-231 cells were stably transfected with control non-targeted shRNA or PELP1 shRNA, and total RNA was isolated for RNA-seq analysis. Our results demonstrated that PELP1 regulates the expression of Myc, E2F and mTOR targets in TNBC.

2022-03-03 | GSE191066 | GEO

Targeting PELP1 oncogenic signaling in TNBC with the small molecule inhibitor SMIP34.

Project description:PurposeTriple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Oncogenic PELP1 is frequently overexpressed in TNBC, and it has been demonstrated that PELP1 signaling is essential for TNBC progression. The therapeutic utility of targeting PELP1 in TNBC, however, remains unknown. In this study, we investigated the effectiveness of SMIP34, a recently developed PELP1 inhibitor for the treatment of TNBC.MethodsTo ascertain the impact of SMIP34 treatment, we used seven different TNBC models for testing cell viability, colony formation, invasion, apoptosis, and cell cycle analysis. Western blotting and RT-qPCR were used to determine the mechanistic insights of SMIP34 action. Using xenograft and PDX tumors, the ability of SMIP34 in suppressing proliferation was examined both ex vivo and in vivo.ResultsTNBC cells' viability, colony formation, and invasiveness were all decreased by SMIP34 in in vitro cell-based assays, while apoptosis was increased. SMIP34 treatment promoted the degradation of PELP1 through the proteasome pathway. RT-qPCR analyses confirmed that SMIP34 treatment downregulated PELP1 target genes. Further, SMIP34 treatment substantially downregulated PELP1 mediated extranuclear signaling including ERK, mTOR, S6 and 4EBP1. Mechanistic studies confirmed downregulation of PELP1 mediated ribosomal biogenesis functions including downregulation of cMyc and Rix complex proteins LAS1L, TEX-10, and SENP3. The proliferation of TNBC tumor tissues was decreased in explant experiments by SMIP34. Additionally, SMIP34 treatment markedly decreased tumor progression in both TNBC xenograft and PDX models.ConclusionsTogether, these findings from in vitro, ex vivo, and in vivo models show that SMIP34 may be a useful therapeutic agent for inhibiting PELP1 signaling in TNBC.

| S-EPMC10224866 | biostudies-literature

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