Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Hypoxia limits the tumor-suppressive effects of C/EBPδ in pancreatic cancer

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is a horrid disease with a terrifyingly low 5- year survival rate of only 12%. While this rate has slightly increased over the past decade, the incidence of PDAC has risen faster, by about 1% every year. Pre-clinical models are being employed with the aim to better understand the underlying tumor biology but sadly, a translation into the clinic often fails due to unforeseen complications. In a previous study, we showed that the transcription factor C/EBPδ has tumor-suppressive effects on PDAC cells in vitro. In this study, we take those findings a step further and assess the effect of C/EBPδ in a preclinical PDAC model in mice. We establish that the lack of oxygen in vivo – hypoxia - counteracts the tumor-suppressive effects of C/EBPδ in PDAC cells and suggest that this is partly mediated by a reciprocal feedback loop between C/EBPδ and HIF-1α. Although RNA-sequencing shows that the tumor-suppressive effects of C/EBPδ are not entirely abrogated under hypoxia, our study demonstrates the importance of considering major physiological parameters in order to make clinically relevant propositions.

ORGANISM(S): Homo sapiens

PROVIDER: GSE226038 | GEO | 2024/09/18

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Hypoxia limits the tumor-suppressive effects of C/EBPδ in pancreatic cancer

Project description:Hypoxia limits the tumor-suppressive effects of C/EBPδ in pancreatic cancer

| PRJNA938416 | ENA

Pediatric AML classification according to C/EBPδ expression

Project description:We examined if pediatric AMLs rank-ordered according to C/EBPδ expression showed the activation of similar pathways. AML samples were dichotomized into groups including the upper quartile (Q1) and the lower three quartiles (Q2-4) according to their C/EBPδ expression values. Moreover, AML samples were associated to French-American-British (FAB) classification.

2016-06-21 | GSE75461 | GEO

C/EBPδ drives key endocrine signals in human fetal membranes at parturition

Project description:Amnion-derived prostaglandin E2 (PGE2) and cortisol are key to labor onset. Identification of the common transcription factor driving the expression of both cyclooxygenase-2 (COX-2) and 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), the key enzymes in their production, may hold the key to the treatment of pre- and post-term labor. Here, we have found that the CCAAT enhancer binding protein δ (C/EBPδ) is such a transcription factor which underlies the feed-forward induction of COX-2 and 11β-HSD1 expression by their own products PGE2 and cortisol in human amnion fibroblasts so that their production would be ensured in the amnion for the onset of labor. Moreover, the abundance of C/EBPδ in amnion increases along with COX-2 and 11β-HSD1 at term and further increases at parturition. Knockout of C/EBPδ in mice delays the onset of labor further supporting the concept. In conclusion, C/EBPδ may serve as a novel pharmaceutical target in the amnion for treatment of pre- and post-term labor.

2021-07-15 | GSE166320 | GEO

C/EBPδ drives key endocrine signals in human fetal membranes at parturition [ChIP-seq]

Project description:Amnion-derived prostaglandin E2 (PGE2) and cortisol are key to labor onset. Identification of the common transcription factor driving the expression of both cyclooxygenase-2 (COX-2) and 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), the key enzymes in their production, may hold the key to the treatment of pre- and post-term labor. Here, we have found that the CCAAT enhancer binding protein δ (C/EBPδ)is such a transcription factor which underlies the feed-forward induction of COX-2 and 11β-HSD1 expression by their own products PGE2 and cortisol in human amnion fibroblasts so that their production would be ensured in the amnion for the onset of labor. Moreover, the abundance of C/EBPδin amnion increases along with COX-2 and 11β-HSD1 at term and further increases at parturition. Knockout of C/EBPδ in mice delays the onset of labor further supporting the concept. In conclusion, C/EBPδmay serve as a novel pharmaceutical target in the amnion for treatment of pre- and post-term labor.

2021-07-15 | GSE166454 | GEO

C/EBPδ drives key endocrine signals in human fetal membranes at parturition [RNA-seq]

2021-07-15 | GSE166453 | GEO

Combating pancreatic cancer with ovarian cancer cells

Project description:Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor, and the five-year survival rate is still less than 5%. However, Gemcitabine, a first-line chemotherapy drug of PDAC, has serious side effects and chemotherapy resistance. It is imperative to find new therapies to treat patients with advanced pancreatic cancer. With the computational screening, we found the gene sginature of ovarian serous carcinoma is anti-correlated with that of PDAC. Then we established an animal model of pancreatic cancer xenografts and injected ovarian cancer cell SKOV3 into xenografts to observe whether the SKOV3 could inhibit the growth of pancreatic cancer. We used RNA-sequencing to compare the tumor treated with SKOV3 to that with normal saline.

2022-08-30 | GSE212173 | GEO

The Janus kinase 1 is critical for the postnatal development of the pancreas and cancer progression

Project description:Inflammatory cytokines promote the development of pancreatic ductal adenocarcinoma (PDAC), but the functions of specific intracellular signaling mediators in this process are less well-defined. In this study, we discovered that the Janus kinase 1 (JAK1) is critical for the early postnatal growth of the exocrine pancreas. Using a ligand-controlled and pancreas-specific knockout in adult mice, we demonstrate that JAK1 deficiency prevents the formation of KRASG12D-induced pancreatic tumors, and we established that JAK1 is essential for the constitutive activation of STAT3 whose activation is a prominent characteristic of PDAC. We identified C/EBPδ as a biologically relevant downstream target of JAK1 signaling, which is upregulated in human PDAC. Reinstating the expression of C/EBPδ was sufficient to rescue the growth of JAK1-deficient tumorspheres. Collectively, the findings of this study suggest that JAK1 executes important functions of inflammatory cytokines through C/EBPδ and may serve as a molecular target for PDAC prevention and treatment.

2024-06-26 | GSE227149 | GEO

Transcriptional profiling of autophagy proficient and compromised cell lines, determined by expression levels of Atg5

Project description:Autophagy is activated in pancreatic ductal adenocarcinoma (PDAC) and is currently being considered a promising therapeutic target in clinical trials. PDAC is a highly lethal disease with incidence rate equalling mortality rate. Main reasons for PDAC lethality are late-stage diagnosis, high agressiveness and metastatic rate, lack of effective treatments as well as specific diagnostic markers. Here we show that varying levels of the Autophagy related gene 5 (Atg5) determine pancreatic tumor formation and malignancy. While homozygous deletion of Atg5 blocks tumor progression in an in vivo model of PDAC, heterozygous deletion increases tumor aggressiveness and metastasis. Further analyses reveal that monoallelic loss of Atg5 affects mitochondrial homeostasis, changes intracellular calcium oscillations, heightens extracellular cathepsin activities , and promotes a pro-tumorigenic inflammatory microenvironment collectively enhancing tumor cell migration, invasion, and metastasis. Future treatments should take into account that variations in the autophagy pathway may have opposing effects on pancreatic tumor load, especially considering the multitude of autophagy inhibitors currently tested in clinical trials.

2018-10-15 | E-MTAB-6275 | biostudies-arrayexpress

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

Project description:By studying a mouse model, as well as human tumors samples and cell lines, we have revealed a tumor suppressive role for Gata6 in the pathogenesis of pancreatic ductal adenocarcinoma (PDAC). In order to understand the mechanism underlying such tumor suppressive function, we analyzed the genome-wide DNA-binding of GATA6 in a human PDAC cell line (PaTu8988S). GATA6 is found to bind the promoter of genes involved in the epithelial differentiation programme, as well as of genes involved in the mesenchymal programme. With this we describe a novel GATA6-dependent mechanism of regulation of EMT. Examination of GATA6 binding to the DNA in a human PDAC cell line

2015-02-03 | E-GEOD-47535 | biostudies-arrayexpress

SMAD2/3 mediate oncogenic effects of TGF-β in the absence of SMAD4

Project description:The tumor suppressive effects of TGF-β are classically associated with the activation of the “canonical” SMAD-mediated pathway, whereas its oncogenic effects are largely attributed to its “non-canonical signaling”. We herein provide evidence of an oncogenic effect for SMAD2 and 3 in response to TGF-β in SMAD4-null cancer cells. Using the CRISPR/Cas9 technology, we report that simultaneous knockout of Smad2 and 3 in Smad4-negative pancreatic ductal adenocarcinoma (PDAC) cells compromises TGF-β-driven collective migration mediated by FAK and Rho/Rac signaling. Moreover, RNA-sequencing analyses highlight a TGF-β gene signature related to aggressiveness mediated by SMAD2 and 3 in the absence of SMAD4. Using PDAC patients cohorts, we reveal that SMAD4-negative tumors with high levels of (phospho)-SMAD2 are more aggressive and have a poorer prognosis. Thus, loss of SMAD4 tumor suppressive activity in PDAC is associated with oncogenic gain-of-function of SMAD2 and 3 and the onset of associated deleterious effects.

2022-10-09 | GSE178714 | 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