Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The effect of CHRDL2 overexpression on gene expression in CACO2 CRC cells

ABSTRACT: Chordin-like-2 (CHRDL2) is a secreted BMP antagonist, with overexpression and genomic variants associated with colorectal cancer (CRC) risk. BMP signalling in the normal intestinal epithelium operates in opposition to the WNT signalling pathway, which maintains stem-cells and self-renewal. Elevated WNT signalling leads to expansion of the stem cell compartment and hyperproliferation, defining characteristics of CRC. Here, we explored the impact of CHRDL2 overexpression on CRC cells to investigate whether CHRDL2's inhibition of BMP signalling intensified WNT signalling, and enhanced the cancer stem-cell phenotype. RNA-seq analysis revealed that CHRDL2 increased the expression of stem cell markers and well-established cancer-associated pathways. We suggest that CHRDL2 overexpression can augment the stem-cell potential of CRC and normal intestinal cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE253554 | GEO | 2024/01/22

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Genome-wide map of GATA6 DNA binding in human CRC cells

Project description:We describe the genome-wide DNA-binding of GATA6 in a human CRC cell line (LS174T). GATA6 is found to bind the promoter of genes involved in the maintenance of intestinal stem cells, including genes of the Wnt and TGFbeta/BMP pathways. With this we describe a novel GATA6-dependent mechanism of stem cell maintenance in colorectal tumors. Examination of GATA6 binding and H3K4me1, H3K4me3 and H3K27ac levels in a human CRC cell line by Chromatin immunoprecipitation followed by deep sequencing.

2014-05-20 | E-GEOD-49320 | biostudies-arrayexpress

Stabilisation of b-Catenin-WNT signalling by USP10 in APC-truncated colorectal cancer drives cancer stemness and enables super-competitor signalling

Project description:The contribution of deubiquitylating enzymes to b-Catenin stabilisation in intestinal stem cells and colorectal cancer (CRC) is poorly understood. Here, we report the deubiquitylase USP10 as APC-truncation- specific regulator enhancer of b-Catenin stability, potentiating WNT signalling pathway in CRC and cancer stem cells. Mechanistically, interaction studies in various CRC cell lines and in vitro binding studies, together with computational modelling, revealed that USP10 binding to b-Catenin is mediated via its USP10 unstructured N-terminus and requires truncated in the absence of full-length APC. Notably, loss of USP10 in CRISPR engineered intestinal organoids reduces tumorigenic properties of CRC cells and organoids, and blocks the super competitor-properties of APC-mutated intestinal cells, elicits induces the expression of differentiation genes, and opposes the APC-truncated phenotype in an intestinal hyperplasia model of D.melanogaster. Taken together, our findings reveal USP10s role in intestinal tumourigenesis by stabilising b-Catenin, leading to aberrant WNT signalling, enhancing cancer cell stemness and implicate the DUB USP10 as a cancer specific therapeutic vulnerability in Apc truncated CRC.

2024-01-01 | GSE226364 | GEO

Genome-wide map of GATA6 DNA binding in human CRC cells

2014-05-20 | GSE49320 | GEO

The transcription factor GATA6 allows self-renewal of colon adenoma stem cells by repressing BMP gene expression.

Project description:Aberrant activation of WNT signaling and loss of BMP signals represent the two main alterations leading to the initiation of colorectal cancer (CRC). Here we screen for genes required for maintaining the tumor stem cell phenotype and identify the zinc-finger transcription factor GATA6 as key regulator of the WNT and BMP pathways in CRC. GATA6 directly drives the expression of LGR5 in adenoma stem cells while it restricts BMP signaling to differentiated tumor cells. Genetic deletion of Gata6 in mouse colon adenomas increases the levels of BMP factors, which signal to block self-renewal of tumor stem cells. In human tumors, GATA6 represses BMP4 gene expression through binding to a regulatory region that has been previously linked to increased susceptibility to develop CRC. Thus, GATA6 creates a permissive environment for tumor stem cell expansion by controlling the major signaling pathways that influence CRC initiation. Total RNA from biological replicates of VillinCreERT2Gata6+/+Apcfl/fl and VillinCreERT2Gata6fl/flApcfl/fl colon adenoma tumor organoids grown for one week in control media (see growth protocol).Total RNA was extracted using the TRIzolM-BM-. Plus RNA Purification Kit (Life Technologies).

2014-06-19 | E-GEOD-49479 | biostudies-arrayexpress

Induction of dorsal mesodermal genes by pinhead and chordin

Project description:Xenopus embryonic ectodermal cells are responsive to various inducing factors. Mesoderm is specified and patterned by extracellular factors including FGF, Nodal, BMP and Wnt families. Pinhead is another secreted protein implicated in mesoderm formation. We found that Pinhead physically interacts with and antagonizes ADMP (anti-dorsalizing morphogenetic protein) that acts as BMP-like protein to promote ventral mesoderm formation. ADMP and BMPs have been shown to cooperate to activate phospho-Smad1 signaling to lead to ventral mesoderm development. Since Chordin is a BMP antagonist, we hypothesized that Pinhead together with Chordin can promote downregulation of phospho-Smad1 signaling that leads to dorsal mesoderm development. RNA sequencing revealed that Pinhead and Chordin synergize in dorsal mesoderm formation in ectodermal explants.

2021-04-19 | GSE168370 | GEO

The transcription factor GATA6 allows self-renewal of colon adenoma stem cells by repressing BMP gene expression.

2014-06-19 | GSE49479 | GEO

Identification of beta-cetenin/TCF4 target genes in LS174T colorectal cancer cells using gene expression arrays

2014-05-20 | GSE56896 | GEO

Identification of GATA6 target genes in LS174T colorectal cancer cells using gene expression arrays

2014-05-20 | GSE56895 | GEO

Identification of beta-cetenin/TCF4 target genes in LS174T colorectal cancer cells using gene expression arrays

Project description:Aberrant activation of WNT signaling and loss of BMP signals represent the two main alterations leading to the initiation of colorectal cancer (CRC). Here we screen for genes required for maintaining the tumor stem cell phenotype and identify the zinc-finger transcription factor GATA6 as key regulator of the WNT and BMP pathways in CRC. GATA6 directly drives the expression of LGR5 in adenoma stem cells while it restricts BMP signaling to differentiated tumor cells. Genetic deletion of Gata6 in mouse colon adenomas increases the levels of BMP factors, which signal to block self-renewal of tumor stem cells. In human tumors, GATA6 competes with beta-catenin/TCF4 for binding to a distal regulatory region of the BMP4 locus that has been previously linked to increased susceptibility to develop CRC. Hence, GATA6 creates a permissive environment for tumor stem cell expansion by controlling the major signaling pathways that influence CRC initiation. A 4-hydoxy tamoxifen inducible system was used to inducibly block beta-catenin/TCF activity for a period of 36h. Briefly, the ERT2 domain from the pCMV-CRE-ERT2 (Feil et al., 1996) was amplified by PCR and cloned into a modified FUGW lentiviral vector backbone (Lois et al., 2002). NTCF was then amplified byPCR from the pCDNA3.1-NTCF-NLS (van de Wetering et al., 2002) and cloned in frame upstream of the ERT2 from the FUW-CMV-ERT2 (ET) to create the FUW-CMV-NTCF-ERT2 (NET). Total RNA was extracted using the TRIzolM-BM-. Plus RNA Purification Kit (Life Technologies).

2014-05-20 | E-GEOD-56896 | biostudies-arrayexpress

BMP suppresses Wnt signaling via the Bcl11b-regulated NuRD complex to maintain Lgr5+ intestinal stem cells

Project description:Lgr5+ intestinal stem cells (ISCs) play crucial roles in maintenance of the intestinal epithelium renewal and regeneration after injury. The mechanism underlying the interplay between Wnt and BMP signaling is not fully understood. Here we report that Bcl11b, which is downregulated by BMP signaling, enhances Wnt signaling to maintain Lgr5+ ISCs and promote the regeneration of the intestinal epithelium following damage. Conditional inactivation of the Bcl11b gene leads to a significant decrease of Lgr5+ ISCs in both mouse intestinal crypts and cultured organoids. Mechanistically, BMP suppresses the expression of Bcl11b, which can positively regulate Wnt target genes by inhibiting the function of the Nucleosome Remodeling and Deacetylase (NuRD) complex and facilitating the β-catenin-TCF4 interaction. Bcl11b can also promote intestinal epithelium repair after injuries elicited by both irradiation and DSS-induced inflammation. Furthermore, Bcl11b deletion prevents proliferation and tumorigenesis of colorectal cancer cells. Together, our findings suggest that BMP balances Wnt signaling via Bcl11b to delicately regulate the homeostasis and regeneration of the intestinal epithelium.

2024-10-15 | GSE255138 | GEO

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