Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA317909 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We searched for candidate genes responsible for Epithelial-to-mesenchymal transition (EMT) by microarray analysis of cultured lung cancer cells with or without the property of spheroid formation. We found increased expression of a variety of adhesion molecules in cancer stem-like cells, including Collagen XVII. Further functional assays and signaling pathway were also investigated.
2016-12-07 | GSE80097 | GEO
Project description:Mps One Binder Kinase Activator (MOB)1A/1B are core components of the Hippo pathway. These proteins, which coactivate LArge Tumor Suppressor homolog (LATS) kinases, are also tumor suppressors. To investigate MOB1A/B’s roles in normal physiology and lung cancer, we generated doxycycline (Dox)-inducible, bronchioalveolar epithelium–specific, null mutations of MOB1A/B in mice [SPC-rtTA/(tetO)7-Cre/Mob1aflox/flox/Mob1b-/-; termed luMob1DKO) mice]. Most mutants (70%) receiving Dox in utero [luMob1DKO (E6.5-18.5) mice] died of hypoxia within 1hr post-birth. Their alveolar epithelial cells showed increased proliferation, impaired YAP1/TAZ-dependent differentiation, and decreased surfactant protein production, all features characteristic of human respiratory distress syndrome (RDS). Intriguingly, mutant mice that received Dox postnatally [luMob1DKO (P21–41) mice] did not develop spontaneous lung adenocarcinomas, and urethane treatment-induced lung tumor formation was decreased (rather than increased). Lungs of luMob1DKO (P21–41) mice exhibited increased detachment of bronchiolar epithelial cells and decreased numbers of the bronchioalveolar stem cells (BASCs) thought to initiate lung adenocarcinomas. YAP1/TAZ-NKX2.1-dependent expression of collagen XVII, a key hemidesmosome component, was also reduced. Thus, a MOB1-YAP1/TAZ-NKX2.1 axis is essential for normal lung homeostasis and expression of the collagen XVII protein necessary for alveolar stem cell maintenance in the lung niche.
2017-03-29 | GSE93778 | GEO
Project description:Lung cancer is a fatal complication of idiopathic pulmonary fibrosis (IPF) with a poor prognosis. Current treatments are insufficient in improving the prognosis of lung cancer patients with comorbid idiopathic pulmonary fibrosis (IPF-LC). Senescent fibroblasts play a pivotal role within the tumor microenvironment, influencing tumor progression by secreted exosomes. With evidence that fibroblast senescence is an important mechanism of IPF, we sought to investigate the impact of senescent IPF lung fibroblast-derived exosomes on non-small cell lung cancer (NSCLC). Our results show that IPF fibroblasts (diseased human lung fibroblasts, DHLF) express significant senescence markers, promoting NSCLC proliferation, invasion, and epithelial-mesenchymal transition. Specifically, we observed senescent DHLFs secret more exosomes (DHLF-exosomes), which could enhance proliferation and colony-forming ability of cancer cells. Proteomic analysis of DHLF-exosomes identified upregulation of SASP factors, notably MMP1, which activates the surface receptor PAR1. Knocking down MMP1 or using PAR1 inhibitors reduced the tumor-promoting effects of DHLF-exosomes in vivo and in vitro. Mechanistically, MMP1 acted via activating the PI3K-AKT-mTOR pathway. In conclusion, our results suggest that exosomal MMP1 derived from senescent IPF fibroblasts promotes NSCLC proliferation and colony formation by targeting PAR1 and activating the PI3K-AKT-mTOR pathway. These findings provide a novel therapeutic approach for patients with IPF-LC.
2024-10-21 | GSE279637 | GEO
Project description:Unsupervised classification of gene expression profiles has resulted in the identification of biologically and clinically distinct colon cancer subtypes (CCSs). The subtype that associates with poor clinical outcome displays a mesenchymal gene expression profile. No driver mutation has been identified for this category and patients are heterogeneous with regard to commonly used clinical markers. Here we report a regulatory network consisting of the miR-200 family members that tunes the majority of genes differentially expressed in the poor prognosis CCS, including genes involved in the epithelial-mesenchymal transition (EMT) process. Our data indicate that the epigenetic silencing of the miR-200 family by promoter methylation is identifying the mesenchymal CCS and is predictive of disease-free survival in this malignancy. We demonstrate that the molecular features of poor prognosis colon cancer - expression of EMT-associated genes and miR-200 promoter methylation - can already be installed at the premalignant stage, suggesting a highly malignant potential of specific colon cancer precursor lesions. Four colorectal cancer cell lines that display methylated miR-200 loci have been used to overexpress miR-200 family members from both loci separatedly or simultaneously.
2015-09-01 | E-GEOD-65551 | biostudies-arrayexpress
Project description:Tumors that show evidence of epithelial to mesenchymal transition (EMT) have been associated with metastasis, drug resistance, and poor prognosis. EMT may alter the molecular requirements for growth and survival in different contexts, but the underlying mechanisms remain incomplete. Given the heterogeneity along the EMT spectrum between and within tumors it is important to define the requirements for growth and survival in cells with an epithelial or mesenchymal phenotype to maximize therapeutic efficacy. We have established an inducible cell line model in which a tamoxifen regulatable Twist-ER fusion protein is stably expressed in the H358 non-small cell lung cancer cell line. Upon tamoxifen addition, cells undergo EMT and provide a system in which we can compare the growth and survival requirements directly related to EMT, removing confounding factors present when comparing different cell lines. H358 cells stably expressing either GFP or TwistER were treated for 12 days in culture with 100nM 4-hydroxytamoxifen followed by RNA isolation. Three biological replicates of each condition were collected.
2014-01-01 | E-GEOD-52308 | biostudies-arrayexpress
Project description:Lung cancer remains the leading cause of cancer-related death due to poor treatment responses and resistance arising from tumor heterogeneity. Here we show that adverse prognosis associated with epigenetic silencing of the tumour suppressor RASSF1A is due to increased deposition of extracellular matrix (ECM), tumour stiffness and metastatic dissemination in vitro and in vivo. We find that lung cancer cells with RASSF1A promoter methylation display constitutive nuclear YAP1 and expression of collagen prolylhydroxylase (P4HA2) which increases collagen deposition. Furthermore, we identify that elevated collagen creates a stiff-ECM which in turn triggers cancer stem-like programming and metastatic dissemination in vivo. Re-expression of RASSF1A or inhibition of P4HA2 activity reverse these effects and increase markers of lung differentiation (TTF-1, Mucin5B). Our study identifies RASSF1A as a clinical biomarker associated with mechanical properties of ECM which increases levels of cancer stemness and risk of metastatic progression in lung adenocarcinoma. Moreover, we highlight P4HA2 as a potential target for uncoupling ECM signals that support cancer stemness.
2019-05-20 | PXD012694 | Pride
Project description:We have investigated Perineural invasion (PNI) and epithelial-mesenchymal transition (EMT) related gene expression profiles of PC cell lines. In this dataset, we include the expression data obtained from laminin binding O-glycan high or low androgen-independent PC cells. These data are used to obtain 70 genes that are differentially expressed in response to cell migraton signal via laminin receptors.
2017-04-30 | GSE62576 | GEO
Project description:GTP cyclohydrolase (GTPCH) is encoded by the GCH1 gene. Its physiological activity is tightly regulated for neurotransmission, immune and vascular functions. We have shown previously that GTPCH is highly expressed in breast tumors. However, the protumorigenic mechanisms of GTPCH remain unknown. Here we show that GTPCH transforms the immortalized MCF10A breast epithelia and induces epithelial-to-mesenchymal transition (EMT). GTPCH-induced EMT is mediated by epidermal growth factor receptor (EGFR), through HSP90 and activator of HSP90 ATPase1 (AHA1). The GCH1 knockout or inhibition attenuates breast tumor growth in vitro and in vivo, and sensitizes the cells to hormone therapy in cultures. High GCH1 expression is significantly correlated with worse prognosis, chiefly ER+, PR+ and tamoxifen-treated tumors. Thus, GTPCH is an emerged cancer target.
2022-05-11 | PXD019676 | Pride
Project description:We focus on cancer-associated fibroblasts (CAFs) as an active component of the tumor microenvironment. The transcriptome profiling and analysis of CAFs isolated from breast cancer skin metastasis, cutaneous basal cell carcinoma and squamous cell carcinoma arising from oral cavity mucous membrane unravelled major gene candidates such as the IL-6, VEGF-A and MFGE8 that induced the expression of several markers associated with poor prognosis and epithelial-to-mesenchymal transition in co-cultivated EM-G3 breast cancer cells.
2023-10-02 | E-MTAB-12994 | biostudies-arrayexpress
Project description:Recently, several research groups have identified the mesenchymal subtype of serous OvCa on the basis of transcriptome data and its potential correlation with poor prognosis. We set out to define the regulatory mechanisms underlying the distinct gene expression profiles of serous OvCa using a network-based approach involving multiple molecular modalities such as gene expression and microRNA (miR) expression. Our study demonstrated that the mir-508-3p presented as the most powerful determinant of mesenchymal subtype-specific gene expression, tuning the majority of genes differentially expressed in the poor prognosis subtype, including genes associated with the epithelial–mesenchymal transition (EMT) program. Consequent functional experiments illustrate that miR-508-3p inhibition promoted EMT process, in vitro cell migration and invasion, and in vivo cancer metastasis.
2018-06-01 | GSE108863 | GEO