Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

PARCB Project: Reprogramming normal human epithelial tissues to a common, lethal neuroendocrine cancer lineage

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

ORGANISM(S): Homo sapiens

PROVIDER: GSE118207 | GEO | 2018/10/05

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Reprogramming normal human epithelial tissues to a common, lethal neuroendocrine cancer lineage.

Project description:The use of potent therapies inhibiting critical oncogenic pathways active in epithelial cancers has led to multiple resistance mechanisms, including the development of highly aggressive, small cell neuroendocrine carcinoma (SCNC). SCNC patients have a dismal prognosis due in part to a limited understanding of the molecular mechanisms driving this malignancy and the lack of effective treatments. Here, we demonstrate that a common set of defined oncogenic drivers reproducibly reprograms normal human prostate and lung epithelial cells to small cell prostate cancer (SCPC) and small cell lung cancer (SCLC), respectively. We identify shared active transcription factor binding regions in the reprogrammed prostate and lung SCNCs by integrative analyses of epigenetic and transcriptional landscapes. These results suggest that neuroendocrine cancers arising from distinct epithelial tissues may share common vulnerabilities that could be exploited for the development of drugs targeting SCNCs.

| S-EPMC6414229 | biostudies-literature

Reprogramming normal human epithelial tissues to a common, lethal neuroendocrine cancer lineage (RNA-seq)

Project description:Small cell carcinomas from different tissues exhibit transcriptional and epigenetic convergence and suggest common vulnerabilities for therapies

2018-10-05 | GSE118206 | GEO

Reprogramming normal human epithelial tissues to a common, lethal neuroendocrine cancer lineage (ATAC-seq)

Project description:Small cell carcinomas from different tissues exhibit transcriptional and epigenetic convergence and suggest common vulnerabilities for therapies

2018-10-05 | GSE118204 | GEO

Reprogramming normal human epithelial tissues to a common, lethal neuroendocrine cancer lineage (Whole Exome-seq)

Project description:Small cell carcinomas from different tissues exhibit transcriptional and epigenetic convergence and suggest common vulnerabilities for therapies

2018-10-05 | GSE118205 | GEO

PARCB Project: Reprogramming normal human epithelial tissues to a common, lethal neuroendocrine cancer lineage

Project description:PARCB Project: Reprogramming normal human epithelial tissues to a common, lethal neuroendocrine cancer lineage

| PRJNA484866 | ENA

Reprogramming normal human epithelial tissues to a common, lethal neuroendocrine cancer lineage (ATAC-seq)

Project description:Reprogramming normal human epithelial tissues to a common, lethal neuroendocrine cancer lineage (ATAC-seq)

| PRJNA484868 | ENA

Reprogramming normal human epithelial tissues to a common, lethal neuroendocrine cancer lineage (RNA-seq)

Project description:Reprogramming normal human epithelial tissues to a common, lethal neuroendocrine cancer lineage (RNA-seq)

| PRJNA484869 | ENA

Reprogramming normal human epithelial tissues to a common, lethal neuroendocrine cancer lineage (Whole Exome-seq)

Project description:Reprogramming normal human epithelial tissues to a common, lethal neuroendocrine cancer lineage (Whole Exome-seq)

| PRJNA484870 | ENA

Organoid cultures from normal and cancer-prone human breast tissues preserve complex epithelial lineages.

Project description:Recently, organoid technology has been used to generate a large repository of breast cancer organoids. Here we present an extensive evaluation of the ability of organoid culture technology to preserve complex stem/progenitor and differentiated cell types via long-term propagation of normal human mammary tissues. Basal/stem and luminal progenitor cells can differentiate in culture to generate mature basal and luminal cell types, including ER+?cells that have been challenging to maintain in culture. Cells associated with increased cancer risk can also be propagated. Single-cell analyses of matched organoid cultures and native tissues by mass cytometry for 38 markers provide a higher resolution representation of the multiple mammary epithelial cell types in the organoids, and demonstrate that protein expression patterns of the tissue of origin can be preserved in culture. These studies indicate that organoid cultures provide a valuable platform for studies of mammary differentiation, transformation, and breast cancer risk.

| S-EPMC7136203 | biostudies-literature

Stromal epigenetic alterations drive metabolic and neuroendocrine prostate cancer reprogramming.

Project description:Prostate cancer is an androgen-dependent disease subject to interactions between the tumor epithelium and its microenvironment. Here, we found that epigenetic changes in prostatic cancer-associated fibroblasts (CAF) initiated a cascade of stromal-epithelial interactions. This facilitated lethal prostate cancer growth and development of resistance to androgen signaling deprivation therapy (ADT). We identified a Ras inhibitor, RASAL3, as epigenetically silenced in human prostatic CAF, leading to oncogenic Ras activity driving macropinocytosis-mediated glutamine synthesis. Interestingly, ADT further promoted RASAL3 epigenetic silencing and glutamine secretion by prostatic fibroblasts. In an orthotopic xenograft model, subsequent inhibition of macropinocytosis and glutamine transport resulted in antitumor effects. Stromal glutamine served as a source of energy through anaplerosis and as a mediator of neuroendocrine differentiation for prostate adenocarcinoma. Antagonizing the uptake of glutamine restored sensitivity to ADT in a castration-resistant xenograft model. In validating these findings, we found that prostate cancer patients on ADT with therapeutic resistance had elevated blood glutamine levels compared with those with therapeutically responsive disease (odds ratio = 7.451, P = 0.02). Identification of epigenetic regulation of Ras activity in prostatic CAF revealed RASAL3 as a sensor for metabolic and neuroendocrine reprogramming in prostate cancer patients failing ADT.

| S-EPMC6159981 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data