Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Grainyhead-like-2, an epithelial master programmer, promotes interferon induction and suppresses breast cancer recurrence [RNA-Seq]

ABSTRACT: Type-I and -III interferons play a central role in immune rejection of pathogens and tumors, thus promoting immunogenicity and suppressing tumor recurrence. Differentiation of embryonic stem cells to pluripotent epithelial cells activates the interferon response during development, raising the question of whether epithelial vs. mesenchymal gene signatures in cancer potentially regulate the interferon pathway as well. Here we show that Grainyhead-like-2 (GRHL2), a master programmer of epithelial cell identity, promotes the type-I and -III interferon responses to double-strand RNA, an important ligand for immune rejection of tumors via interferons. The positive effects of GRHL2 were mediated by enhanced IRF3 and relA/NF-kB activation, upregulation of IRF1, and a functional GRHL2 binding site identified in the IFNL1 promoter. In addition, time to recurrence in breast cancer correlated positively with GRHL2 protein expression, indicating that GRHL2 is a tumor recurrence suppressor, consistent with its enhancement of interferon responses. These observations demonstrate that epithelial cell identity supports interferon responses in the context of cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE241852 | GEO | 2024/04/26

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Grainyhead-like-2, an epithelial master programmer, promotes interferon induction and suppresses breast cancer recurrence [ATAC-seq]

Project description:Type-I and -III interferons play a central role in immune rejection of pathogens and tumors, thus promoting immunogenicity and suppressing tumor recurrence. Differentiation of embryonic stem cells to pluripotent epithelial cells activates the interferon response during development, raising the question of whether epithelial vs. mesenchymal gene signatures in cancer potentially regulate the interferon pathway as well. Here we show that Grainyhead-like-2 (GRHL2), a master programmer of epithelial cell identity, promotes the type-I and -III interferon responses to double-strand RNA, an important ligand for immune rejection of tumors via interferons. The positive effects of GRHL2 were mediated by enhanced IRF3 and relA/NF-kB activation, upregulation of IRF1, and a functional GRHL2 binding site identified in the IFNL1 promoter. In addition, time to recurrence in breast cancer correlated positively with GRHL2 protein expression, indicating that GRHL2 is a tumor recurrence suppressor, consistent with its enhancement of interferon responses. These observations demonstrate that epithelial cell identity supports interferon responses in the context of cancer.

2024-04-26 | GSE241853 | GEO

Identical transcriptome reprograming by interferon lambda 3 and 4 and its absence in IFNLR1 or IL10R2 deficient cells rules out the IFNL4 non-canonical signaling hypothesis

Project description:Lambda interferons IFNL1-3 mediate antiviral immunity by inducing interferon sensitive genes (ISGs) in epithelial tissues. Contrarily, a variant creating the functional gene IFNL4 is associated with impaired clearance of hepatitis C virus (HCV) despite of higher liver expression of ISGs in untreated HCV patients. We aimed to explore IFNL4 signaling mechanism by comparing expression profiles from human hepatic cell line clones with genetic modifications influencing the ISG signaling pathway (IFNLR1/IL10R2 knockouts, IFNL4/IFNL3 expression stimulation by transfection).

2021-12-31 | E-MTAB-8916 | biostudies-arrayexpress

Inactivation of Zeb1 in GRHL2-deficient mouse embryos rescues mid-gestation viability and secondary palate closure

Project description:Aim: Identify molecular pathways controlling palate closure Methods: First pharygneal arch of wild-type and Grhl2-/- e10.5 moues embryos was subjected to RNAseq Results: Grhl2-/- PA1 displayed a shift from epithelial to mesenchymal gene expression Conclusions: Grhl2 maintains epithelial cellular identity during palate closure

2020-03-03 | GSE106130 | GEO

Grhl2 regulated genes in the mouse lung epithelial MLE15 cell line

Project description:The Grainyhead family of transcription factors controls morphogenesis and differentiation of epithelial cell layers in multicellular organisms by regulating cell junction- and proliferation-related genes. Grainyhead-like 2 (Grhl2) is expressed in developing mouse lung epithelium and is required for normal lung organogenesis. The specific epithelial cells expressing Grhl2 and the genes regulated by Grhl2 in normal lungs are mostly unknown. In these studies, we identified the NK2 homeobox 1 transcription factor (Nkx2-1) as a direct transcriptional target of Grhl2. By binding and transcriptional assays, and by confocal microscopy we showed that these two transcription factors form a positive feed-back loop in vivo and in cell lines, and are co-expressed in lung bronchiolar and alveolar type II cells. The morphological changes observed in flattening lung alveolar type II cells in culture are associated with down-regulation of Grhl2 and Nkx2-1. Reduction of Grhl2 in lung epithelial cell lines results in lower expression levels of Nkx2-1 and of known Grhl2 target genes. By microarray analysis we identified that in addition to Cadherin1 and Claudin4, Grhl2 regulates other cell interaction genes such as semaphorins and their receptors, which also play a functional role in developing lung epithelium. Impaired collective cell migration observed in Grhl2 knockdown cell monolayers is associated with reduced expression of these genes and may contribute to the altered epithelial phenotype reported in Grhl2 mutant mice. Thus, Grhl2 functions at the nexus of a novel regulatory network, connecting lung epithelial cell identity, migration and cell-cell interactions. To identify genes regulated by GRHL2 in lung epithelial cells, we performed cDNA microarray analyses in MLE15 cells transduced with Grhl2-shRNA and compared to a non-silencing control. Independent transductions of MLE15 cells using Grhl2-shRNA (n=3) and a non-silencing control (n=2) were analyzed.

2012-09-10 | E-GEOD-40729 | biostudies-arrayexpress

Elevated GRHL2 imparts plasticity in estrogen receptor positive breast cancer cells [ChIP-Seq]

Project description:Estrogen receptor (ER) positive breast cancer is characterized by a late recurrence following initial treatment. The epithelial cell fate transcription factor Grainyhead-like protein 2 (GRHL2) is amplified in ER positive breast cancers and is indicative of poorer prognosis as compared to ER negative breast cancer. To understand how GRHL2 contributes to progression, GRHL2 was overexpressed in ER positive cells. To determine how GRHL2 overexpression affects GRHL2 binding to DNA, ChIP sequencing was conducted to evaluate binding intensity and location.

2024-08-25 | GSE272059 | GEO

Elevated GRHL2 imparts plasticity in estrogen receptor positive breast cancer cells [RNA-seq]

Project description:Estrogen receptor (ER) positive breast cancer is characterized by a late recurrence following initial treatment. The epithelial cell fate transcription factor Grainyhead-like protein 2 (GRHL2) is amplified in ER positive breast cancers and is indicative of poorer prognosis as compared to ER negative breast cancer. To understand how GRHL2 contributes to progression, GRHL2 was overexpressed in ER positive cells. To examine gene expression changes from elevated GRHL2 levels, RNA-sequencing was performed to better comprehend how high GRHL2 may change its transcriptional activity.

2024-08-25 | GSE272061 | GEO

Type III interferons induce pyroptosis in gut epithelial cells and impair tissue repair upon intestinal injury.

Project description:Tissue damage and repair are hallmarks of inflammation. Despite a wealth of information on the mechanisms that govern tissue damage, mechanistic insight on how inflammation affects repair is lacking. Here, we investigated how interferons influence tissue repair after damage to the intestinal mucosa. We found that type III, not type I or II, interferons delay epithelial cell regeneration by inducing the upregulation of Z-DNA-binding protein 1 (ZBP1). Z-nucleic acids formed following intestinal damage are sensed by ZBP1, leading to Caspase-8 activation, and cleavage of Gasdermin C (GSDMC). Cleaved GSDMC drives epithelial cell death by pyroptosis and delays repair of the large or small intestine after colitis or irradiation, respectively. The type III interferon/ZBP1/Caspase-8/GSDMC axis is also active in patients with inflammatory bowel disease (IBD). Our findings highlight the capacity of type III interferons to delay gut repair, which has important implications for IBD patients or individuals exposed to radiation therapies.

2024-11-01 | GSE277150 | GEO

Type III interferons induce pyroptosis in gut epithelial cells and impair tissue repair upon intestinal injury.

Project description:Tissue damage and repair are hallmarks of the inflammatory process. Despite a wealth of information on the mechanisms that govern tissue damage, mechanistic insight on how inflammatory mediators affect repair is lacking. Here, we investigated how interferons influence tissue repair after damage to the intestinal mucosa driven by inflammation or genotoxicity. We found that type III, but not type I or II, interferons delay epithelial cell regeneration by inducing the upregulation of Z-DNA-binding protein 1 (ZBP1). Z-nucleic acids formed during the damage and repair process are then sensed by ZBP-1, leading to Caspase-8 activation, and cleavage of Gasdermin C (GSDMC). Cleaved GSDMC drives epithelial cell death by pyroptosis and delays the re-epithelialization of the large or small intestine after colitis or irradiation, respectively. We also found that the type III interferon/ZBP1/Caspase-8/GSDMC pathway is activated in patients with inflammatory bowel disease (IBD). Our findings highlight a molecular signaling cascade initiated by type III interferons that delays intestinal tissue repair, which has important implications for IBD patients or individuals exposed to radiation therapies.

2024-11-01 | GSE276837 | GEO

Grhl2 regulated genes in the mouse lung epithelial MLE15 cell line

2012-09-10 | GSE40729 | GEO

Population context drives cell-to-cell variability in interferon response in epithelial cells

Project description:Isogenic cells respond in a heterogeneous manner to interferon. Using a micropatterning approach combined with high-content imaging and spatial analyses, we characterized how the population context (position of a cell with respect to neighboring cells) of epithelial cells affects single cell response to interferons. We identified that cells at the edge of cellular colonies are more responsive than cells embedded within colonies. We determined that this spatial heterogeneity in interferon response resulted from the polarized basolateral interferon receptor distribution, making cells located in the center of cellular colonies less responsive to ectopic interferon stimulation. This was conserved across cell lines and primary cells originated from epithelial tissues. Finally, we demonstrated that this population context-driven cell-to-cell variability influences the outcome of viral infection, as cells embedded within cellular colonies are not protected by interferons and therefore more susceptible to infection. Our data highlights that the behavior of isolated cells does not directly translate to their behavior in a population, placing the population context as one important factor influencing cell-to-cell heterogeneity during interferon response in epithelial cells.

2024-02-07 | PXD047936 | Pride

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