Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

APC and P53 mutations synergize to create a therapeutic vulnerability to NOTUM inhibition in advanced colorectal cancer [scRNA-seq]

ABSTRACT: We thought the immediate effects of APC inactivation may represent unexplored therapeutic vulnerabilities in later stages of advanced colorectal adenocarcinoma. We performed transcriptome profiling of epithelial colon organoids immediately after APC inactivation and cross-referenced gene expression changes to the transcriptomes of several mouse models of colon cancer, including colon tumors in an inflammation-induced CRC model (AOM-DSS), a model of familial adenomatous polyposis (FAP, the Apcmin mouse), and an implantation-based model of metastatic adenocarcinoma using Apc/Trp53/KrasG12D/Smad4 quadruple-mutant tumor organoids15 (APKS tumoroids). Of the roughly 150 genes whose expression is acutely induced upon APC loss and remains elevated in these colon cancer models.

ORGANISM(S): Mus musculus

PROVIDER: GSE198758 | GEO | 2022/12/31

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

APC and P53 mutations synergize to create a therapeutic vulnerability to NOTUM inhibition in advanced colorectal cancer [bulk RNA-seq]

Project description:We report that inactivation of the APC tumor suppressor results in dramatic activation of the NOTUM carboxylesterase, which has potent tumor suppressive activity in APC-null adenomatous epithelium. During progression to adenocarcinoma, APC and TP53 mutations (usually coincident in advanced CRC) synergize, converting NOTUM to an obligate oncoprotein. We provide evidence that the Jekyll-and-Hyde behavior of NOTUM results from its differential activity upon enzymatic targets Glypicans 1 and 4 in early vs. late-stage disease, respectively. Ultimately, we demonstrate that small molecule inhibition of NOTUM activity in a mouse model of metastatic colon cancer is sufficient to arrest primary tumor growth and metastatic colonization. Thus, the extracellular carboxylesterase NOTUM represents a novel therapeutic vulnerability in advanced colorectal adenocarcinomas.

2022-12-31 | GSE198757 | GEO

Gene expression profiles in CDX2P-G19Cre;Apcflox/flox;Tgfbr2flox/flox and CDX2P-G19Cre;Apcflox/flox mouse tumors

Project description:Mutations in TGFBR2, a component of the transforming growth factor (TGF)-β signaling pathway, occur in high-frequency microsatellite instability (MSI-H) colorectal cancer (CRC). In mouse models, Tgfbr2 inactivation in the intestinal epithelium accelerates the development of malignant intestinal tumors in combination with disruption of the Wnt-β-catenin pathway. However, no studies have further identified the genes influenced by TGFBR2 inactivation following disruption of the Wnt-β-catenin pathway. We previously described CDX2P-G19Cre;Apcflox/flox mice, which is stochastically null for Apc in the colon epithelium. In this study, we generated CDX2P-G19Cre;Apcflox/flox;Tgfbr2flox/flox mice, with simultaneous loss of Apc and Tgfbr2. These mice developed tumors, including adenocarcinoma in the proximal colon. We compared gene expression profiles between tumors of the two types of mice using microarray analysis.

2016-11-22 | GSE82133 | GEO

RNA-seq of AKP organoids over different stages of differentiation

Project description:Transcriptomic profiling of mouse tumoroids at early (2 days of Apc restoration) versus late stage differentiation (7 days of Apc restoration)

2020-05-22 | GSE148352 | GEO

APC and P53 mutations synergize to create a therapeutic vulnerability to NOTUM inhibition in advanced colorectal cancer.

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

2022-12-31 | GSE198759 | GEO

APC and P53 mutations synergize to create a therapeutic vulnerability to NOTUM inhibition in advanced colorectal cancer.

Project description:APC and P53 mutations synergize to create a therapeutic vulnerability to NOTUM inhibition in advanced colorectal cancer.

| PRJNA816830 | ENA

Intestinal IKKa is required for tumor initiation in APC mutant mice

Project description:We have generated a mouse model for tumor initiation carrying a mutation in APC and lacking IKKα in intestinal epithelial cells. IKKα-deficient intestinal cells primarily failed to generate adenomas, and the few adenomas arising in this background displayed a significant reduction in cell proliferation. Using an in vitro model for intestinal tumoroids (derived from adenoma initiating cells), we have performed RNA sequencing of wild type and IKKα-deficient intestinal tumoroids. This has demonstrated that epithelial IKKα controls transcription of stem cell-related genes and genes associated with proliferation and apoptosis.

2018-04-17 | GSE101415 | GEO

Alternative splicing induced by bacterial pore-forming toxins sharpens CIRBP-mediated cell response to Listeria infection

Project description:We aimed at identifying the targets of the protein Cold-Inducible RNA-Binding Protein in a human epithelial colon adenocarcinoma cell line (LoVo ATCC CCL-229) in cells infected by Listeria monocytogenes strain LL195 compared to non-infected cells. This set is linked to a previous one referenced on ENA (https://www.ebi.ac.uk/ena/browser/view/PRJEB26593)

2023-10-17 | GSE225516 | GEO

Single-cell transcriptomic survey of adenomatous polyposis patients with germline APC mutations

Project description:Patients with germline APC mutations are recognized by hundreds of adenoma polyps in colon, which will give rise to adenocarcinoma inevitably. Over 700 germline APC mutations have been reported to be the leading cause of adenomatous polyposis. However, the underlying mechanism of APC mutation triggered colonic cancer remains mysterious. Here, using a modified STRT-seq protocol, we analyzed over 4000 single cells from the four matching adenomatous polyposis, adenocarcinoma, adjacent normal colon tissue and one lymphatic metastasis from four adenomatous polyposis patients with APC mutations. We identified the main cell types existed in human intestine such as B cells, mast cells, T cells, macrophage cells, endothelial cells, stromal cells and epithelial cells. And the proportional changes of various cell types during the development of adenoma were showed. The transcriptomic similarities and differences between adenoma, adenocarcinoma and adjacent normal tissue were comprehensively investigated. For better understanding the tumor progression process, we also take advantage of other genomic signatures, such as SNV and CNV. We found that the gene expression signatures of adenoma and adenocarcinoma were largely similar when compared with adjacent normal tissue. But the mutation accumulation was indeed observed during the progression from adenoma to adenocarcinoma. To summarized, our work will help us accurately investigate the pathogenic mechanism and heterogeneity of APC inactive mutation triggered colonic cancer, which will also help us better understand the non-familial colorectal cancers

2019-10-25 | GSE109308 | GEO

APC and P53 mutations synergize to create a therapeutic vulnerability to NOTUM inhibition in advanced colorectal cancer [scRNA-seq]

Project description:APC and P53 mutations synergize to create a therapeutic vulnerability to NOTUM inhibition in advanced colorectal cancer [scRNA-seq]

| PRJNA816831 | ENA

APC and P53 mutations synergize to create a therapeutic vulnerability to NOTUM inhibition in advanced colorectal cancer [bulk RNA-seq]

Project description:APC and P53 mutations synergize to create a therapeutic vulnerability to NOTUM inhibition in advanced colorectal cancer [bulk RNA-seq]

| PRJNA816832 | ENA

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