Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA120349 | ENA |
REPOSITORIES: ENA
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Project description:Esophageal cancer is one of the deadliest cancers as patients present at late stages of disease. Frequent gene alterations include the loss of E-cadherin and TGFb receptor type II. The goal of this study was to establish a model of esophageal cancer by introducing dominant-negative mutants of E-cadherin and TGFb receptor II. To analyze the functional consequences and gene expression chages induced by E-cadherin and TGFb receptor type II loss in esophageal cancer.
2013-11-12 | GSE19472 | GEO
Project description:Esophageal cancer is one of the deadliest cancers as patients present at late stages of disease. Frequent gene alterations include the loss of E-cadherin and TGFb receptor type II. The goal of this study was to establish a model of esophageal cancer by introducing dominant-negative mutants of E-cadherin and TGFb receptor II. To analyze the functional consequences and gene expression chages induced by E-cadherin and TGFb receptor type II loss in esophageal cancer. Human esophageal keratinocytes were retrovirally transfected with wild-type full length E-cadherin, dominant-negative E-cadherin and dominant-negative TGFb receptor type II. Grown in organotypic cultures on a collagen/matrigel matrix with embedded fibroblast, the generated cell lines were analyzed for their potential to invade into the underlying matrix. Each cell lines was grown in duplicate in organotypic culture and therefore 2 replicates analyzed. Gene expression changes in invasive versus non-invasive areas were analyzed after RNA isolation using laser-capture microdissection resulting in 2 samples representing a normal esophageal epithelium (Ecad), 2 each of dominant-negative Ecad (Ecyto) non-invasive and invasive. To model the genetic alterations in esophageal cancer dominant-negative E-cadherin and dominant-negative TGFb receptor type II (Ecyto-dnTGFR) were expressed and 2 samples each, non-invasive and invasive, analyzed.
2013-11-12 | E-GEOD-19472 | biostudies-arrayexpress
Project description:Recently, we found that a novel Traf2- and Nck-interacting kinase (TNIK) inhibitor, named NCB-0846, was capable of attenuating tumor-initiating cells among human colorectal cancer. The cross link between EMT and cancer stemness has been revealed in several studies and other group showed another TNIK inhibitor named KY-05009 had inhibited the TGF-β-induced EMT. Therefore we evaluated whether this small-molecule compound could have efficacy to inhibit TGF-β-induced EMT. NCB-0846 reduced the expression of mesenchymal markers (Vimentin and N-cadherin) and upregulated the expression of epithelial marker E-cadherin in A549 and H2228 non-small cell lung cancer cells. NCB-0846 suppressed the phosphorylation and nuclear translocation of Smad proteins and also inhibited migration, invasion, and metastasis. NCB-0846 inhibited TGF-β1-induced EMT through the down-regulation of TGF-β receptor-1 (TβRI) in mRNA levels. MiR-186-5p and miR-320 family were identified as candidate miRNAs that could target TβRI and we found that miR-186-5p and miR-320s inhibited TβRI expression. NCB-0846 might be a novel therapeutics drugs that targets the invasion and metastasis through inhibiting TGF-β-induced EMT in lung cancer.
2017-03-08 | GSE95766 | GEO
Project description:Transcriptional Changes when TGF-beta type II receptor is deleted
| PRJNA778251 | ENA
Project description:Inactivation of TGF-beta family signaling is implicated in colorectal tumor progression. Using the cis-Apc/Smad4 mutant mice, a model of invasive colorectal cancer whose TGF-beta family signaling is blocked, we demonstrate here that a novel type of immature myeloid cells (iMCs) is recruited from the bone marrow to the tumor invasion front. These CD34+ iMCs express MMP9/2 and CC-chemokine receptor 1 (CCR1), and migrate toward its ligand CCL9. In the adenocarcinomas, expression of CCL9 is increased in the tumor epithelium. Such changes in the chemokine expression or the CD34+ iMC recruitment are not observed in the Apc (+/–) mice, a model of adenomatous polyposis. By knocking out Ccr1 gene in the cis-Apc/Smad4 mutant mice, we further demonstrate that lack of CCR1 prevents the accumulation of CD34+ iMCs at the invasion front and suppresses tumor invasion. These results indicate that loss of the TGF-beta family signaling in tumor epithelium causes accumulation of iMCs that help tumor invasion. Keywords: disease state analysis
2007-04-25 | GSE6950 | GEO
Project description:Transformed human esophageal keratinocyte cell line EPC2-T (EPC2-hTERT-EGFR-cyclin D1-p53R175H) cells were stimulated with or without 2.5 ng/ml recombinant human TGF-beta1 for 10 days. The above cells were subjected to treatment for 10 days with or without 0.5 µg/ml doxycycline (DOX) to activate tetracycline-inducible (tet-on) ICN1, an active form of Notch1.
2014-12-31 | GSE37994 | GEO
Project description:Vascular endothelial (VE-)cadherin is a homotypic adhesion protein that is expressed selectively by ECs in which it enables formation of tight vessels and regulation of vascular permeability. Since VE-cadherin is also strongly expressed in placental trophoblasts, it is a prime candidate for a molecular mechanism of vascular mimicry by those cells. Here, we show that the VE-cadherin is required for trophoblast migration and endovascular invasion into the maternal decidua. VE-cadherin deficiency results in loss of spiral artery remodeling due to a lack of invasive trophoblasts, leading to decreased flow of maternal blood into the placenta, fetal growth retardation and death. Loss of trophoblast invasion prevents decidualization, extracellular matrix remodeling, and immune cell clearance. These studies identify VE-cadherin as essential for trophoblast migration and coordination of decidual changes during endovascular invasion. They further suggest endothelial proteins such as VE-cadherin that are expressed by trophoblasts may play functionally distinct roles that do not simply mimic those in ECs.
2021-11-30 | GSE189408 | GEO
Project description:Transforming growth factor- (TGF-) signaling is a critical driver of epithelial–mesenchymal transition (EMT) and cancer progression. However, the regulatory roles of long non-coding RNAs (lncRNAs) in TGF--induced EMT and cancer progression are not well understood. Here, we identified an unannotated nuclear lncRNA LETS1 (LncRNA Enforcing TGF- Signaling 1) as a novel TGF-/SMAD target gene. Loss of LETS1 attenuates TGF--induced EMT, migration and extravasation in breast and lung cancer cells. LETS1 potentiates TGF-/SMAD signaling by stabilizing cell surface TGF- type I receptor (TRI) and thereby forms a positive feedback loop. Mechanistically, LETS1 inhibits TRI polyubiquitination by inducing the orphan nuclear receptor 4A1 (NR4A1) expression, a critical determinant of a destruction complex for inhibitory SMAD7. An unbiased interactome analysis identified the Nuclear Factor of Activated T Cells (NFAT5) as a protein partner of LETS1 to mediate activation of NR4A1 promoter. Overall, our findings characterize LETS1 as an EMT-promoting lncRNA and elucidate the mechanism by which nuclear LETS1 potentiates TGF- receptor signaling.
2023-07-31 | PXD037401 | Pride
Project description:To evaluate geneexpression profile in developing joints vs adjacent growth plate in control and TGF-beta type II receptor conditional knock-out in limb mesenchyjme
2012-06-18 | GSE37287 | GEO
Project description:Microarray analysis reveals up-regulation of retinoic acid and hepatocyte growth factor related signaling pathways by pro-insulin C-peptide in kidney proximal tubular cells: Antagonism of the pro-fibrotic effects of TGF-b1 Novel signaling roles for C-peptide have recently been discovered with evidence that it can ameliorate complications of type 1 diabetes. Here we sought to identify new pathways regulated by C-peptide of relevance to the pathophysiology of diabetic nephropathy. Microarray analysis was performed to identify genes regulated by either C-peptide and/or transforming growth factor beta 1 (TGF-β1) in a human proximal tubular cell line, HK-2. Expression of retinoic acid receptor β (RARβ), hepatcoyte growth factor (HGF), cellular retinoic acid binding protein II (CRABPII), vimentin, E-cadherin, Snail and β-catenin was assessed by immunoblotting. The cellular localisation of vimentin and β-catenin was determined by immunocytochemistry. Changes in cell morphology were assessed by phase contrast microscopy. Gene expression profiling demonstrated differential expression of 953 and 1,458 genes after C-peptide exposure for 18h or 48h respectively. From these, members of the anti-fibrotic retinoic acid (RA) and HGF signaling pathways were selected. Immunoblotting demonstrated that C-peptide increased RARβ, CRABPII and HGF. We confirmed a role for RA in reversal of TGF-β1-induced changes associated with epithelial-mesenchymal transition (EMT), including expression changes in Snail, E-cadherin, vimetin and redistribution of β-catenin. Importantly, these TGF-β1-induced changes were inhibited by C-peptide. Further, effects of TGF-β1 on Snail and E-cadherin expression were blocked by HGF and inhibitory effects of C-peptide were removed by blockade of HGF activity. This study identifies a novel role for HGF as an effector of C-peptide, possibly via an RA signaling pathway, highlighting C-peptide as a potential therapy for diabetic nephropathy.
2010-02-11 | GSE20247 | GEO