Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Nanoscale photoproximity labeling of c-Myc predicts cancer specific therapeutic targets

ABSTRACT: Transcription factors (TFs) have long been aspirational therapeutic targets for the treatment of diseases, as their dysregulation is a common mechanism for altered cell states. Despite this, many TFs implicated in disease have disordered structures and lack canonical binding pockets, rendering them non-trivial targets for small molecule-based therapies. Directly inhibiting TF function has proven difficult, but indirect inhibition by targeting the effector molecules that modulate TF function is a promising alternative strategy. Here we report a unified strategy for capturing cancer-specific protein-protein interactions using µMap photoproximity labeling. Using a recently reported intein-based strategy for catalyst conjugation in biochemically intact nuclei, we demonstrate that we can capture unique protein interactomes of c-Myc in androgen receptor dependent and independent prostate cancer cell lines, and that these unique interactors can be mined to identify druggable vulnerabilities. We find that a PC-3 specific Myc interactor, SLK, selectively promotes Myc stabilization and drives epithelial morphology only in androgen receptor negative prostate cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE307813 | GEO | 2025/09/16

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

A bioinformatics approach reveals novel mechanisms of the OVOL transcription factors in the regulation of epithelial-mesenchymal cell programming and cancer progression.

Project description:We find significant evidence of the OVOL, AP1, STAT1, STAT3, and NFKB1 TFs having important roles in MET. We prioritize known gene/drug targets for follow-up in the clinic, and show that the AP1/MYC TF pair is a strong candidate for intervention. Examination of the effects of OVOL1 and OVOL2 overexpression common to prostate cancer and breast cancer models.

2014-03-20 | E-GEOD-51975 | biostudies-arrayexpress

CENTDIST: Discovery of Co-associated Factors by Motif Distribution

Project description:Transcription factors (TFs) do not function alone but work together with other TFs (called co-TFs) in a combinatorial fashion to precisely control the transcription of target genes. Mining co-TFs is thus important to understand the mechanism of transcriptional regulation. Although existing methods can identify co-TFs, their accuracy depends heavily on the chosen background model and other parameters such as the enrichment window size and the PWM score cut-off. In this study, we have developed a novel web-based co-motif scanning program called CENTDIST (http://compbio.ddns.comp.nus.edu.sg/~chipseq/centdist/). In comparison to current co-motif scanning programs, CENTDIST does not require the input of any user-specific parameters and background information. Instead, CENTDIST automatically determines the best set of parameters and ranks co-TF motifs based on their distribution around ChIP-seq peaks. We tested CENTDIST on 14 ChIP-seq datasets and found CENTDIST is more accurate than existing methods. In particular, we applied CENTDIST on an Androgen Receptor (AR) ChIP-seq dataset from a prostate cancer cell line and correctly predicted all known co-TFs (8 TFs) of AR in the top 20 hits as well as discovering AP4 as a novel co-TF of AR (which was missed by existing methods). Taken together, CENTDIST, which exploits the imbalanced nature of co-TF binding, is a user-friendly, parameter-less, and powerful predictive web-based program for understanding the mechanism of transcriptional co-regulation. Genome-wide binding analyses of AP4 in LNCaP with DHT (5alpha-dihydrotestosterone) stimulation using ChIP-Seq.

2012-04-25 | E-GEOD-28857 | biostudies-arrayexpress

Androgen receptor programming in human tissue implicates HOXB13 in prostate pathogenesis [ChIP-Seq]

Project description:The androgen receptor (AR), a nuclear transcription factor (TF), is consistently reprogrammed during prostate tumorigenesis

2015-10-12 | GSE56288 | GEO

Androgen receptor programming in human tissue implicates HOXB13 in prostate pathogenesis [RNA-Seq]

Project description:The androgen receptor (AR), a nuclear transcription factor (TF), is consistently reprogrammed during prostate tumorigenesis

2015-10-12 | GSE70078 | GEO

The effects of enzalutamide on androgen-dependent and androgen-independent prostate cancer cells.

Project description:To investigate the mechanisms of drug resistance and castration resistance in prostate cancer, we performed proteomic sequencing on androgen-dependent prostate cancer cells (LNCaP) and androgen-independent cells (AI) treated with enzalutamide.

2024-11-26 | PXD058261 |

Single-minded homolog 2 resides in the chromatin protein network of androgen receptor and modulates gene expression in prostate cancer cells Single-minded homolog 2 resides in the chromatin protein network of androgen receptor and modulates gene expression in prostate cancer cells

Project description:We investigated the composition of chromatin protein network around endogenous androgen receptor (AR) in VCaP castration resistant prostate cancer cells using recently developed chromatin-directed proteomic approach called ChIP-SICAP . The androgen-induced AR chromatin protein network contained expected TFs, e.g. HOXB13, chromatin remodeling proteins, e.g. SMARCA4, and several novel candidates not previously associated with AR, e.g. prostate cancer biomarker SIM2. Based on these findings, the role of SMARCA4 and SIM2 was further characterized at AR chromatin domains . Silencing of SIM2 altered chromatin accessibility at a similar number of AR-binding sites as SMARCA4, an established ATPase subunit of the BAF chromatin remodeling complex, often aberrantly expressed in prostate cancer. Despite the wide co-occurrence on chromatin of SMARCA4 and AR, depletion of SMARCA4 influenced chromatin accessibility and expression of a restricted set of AR target genes, in particular those involved in cell morphogenetic changes in epithelial-mesenchymal transition. Silencing of SIM2, in turn, affected the expression of a much larger group of androgen-regulated genes, e.g. those involved in cellular responses to external stimuli and steroid hormone stimulus. The silencing also reduced proliferation of VCaP cells and tumor size in chick embryo chorioallantoic membrane assay, further suggesting the importance of SIM2 in the regulation prostate cancer cells.

2021-06-17 | PXD025193 | Pride

Effect of castration, bicalutamide, and enzalutamide on androgen receptor binding in Hi-Myc mouse prostate tumors

Project description:Effect of castration, bicalutamide, and enzalutamide on androgen receptor binding in Hi-Myc mouse prostate tumors

2015-10-01 | GSE62645 | GEO

N-Myc-mediated epigenetic reprogramming drives lineage plasticity in advanced prostate cancer [RNA-seq]

Project description:Despite recent advances in highly effective androgen receptor (AR)-directed therapies for the treatment of prostate cancer, a significant subset of patients with resistant disease develop AR-null, androgen signaling-indifferent neuroendocrine prostate cancer (NEPC). A majority of these NEPC cases that arise following anti-androgen therapy are driven by the aberrant expression of the transcription factor N-Myc. To define the cell lineage states associated with the development of prostate cancer resistance phenotypes, we analyzed whole transcriptome data from a cohort of primary and metastatic tumors compared to benign tissues. NEPC tumors are significantly enriched for stem cell genes associated with embryonic and neural crest lineages, as well as for neural lineage-defining genes. Analysis of the N-Myc transcriptome, cistrome and chromatin-bound interactome using in vivo (GEMM and human xenografts), in vitro (human prostate cancer cell lines) and ex vivo models (NEPC-patient-derived organoids) revealed that the N-Myc cistrome is androgen-dependent and drives a transcriptional program that leads to epithelial plasticity and the acquisition of clinically-relevant neural lineage markers. Moreover, we show that histone marks specifically associated with lineage-defining genes are epigenetically reprogrammed by N-Myc. Finally, we demonstrate how N-Myc-induced gene expression and epigenetic changes can accurately classify patients with advanced prostate cancer which may provide a molecular signature to inform future therapeutic strategies.

2019-08-26 | GSE117305 | GEO

N-Myc-mediated epigenetic reprogramming drives lineage plasticity in advanced prostate cancer [ChIP-seq]

2019-08-26 | GSE117304 | GEO

CENTDIST: Discovery of Co-associated Factors by Motif Distribution

2012-04-25 | GSE28857 | GEO