Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA386923 | ENA |
REPOSITORIES: ENA
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Project description:Importance of growth factor (GF) signaling in cancer progression is widely acknowledged. Transforming growth factor beta (TGFβ) and and hepa- tocyte growth factor (HGF) are known to play a key role in epithelial-to- mesenchymal transition (EMT) and metastatic cell transformation that are characterized by distinctive alterations in cell mechanical architecture and behavior towards a more robust and motile single cell phenotype. How- ever, molecular mechanisms mediating cancer type specific enhancement of cell mechanical properties in response to growth factors remain unlighted. Here, we combine high-throughput mechanical cell phenotyping, microarray analysis and gene-silencing to dissect molecular mediators of GF-induces cell mechanical enhancement in non-small-cell lung adenocarcinoma (NSCLC). Our experimental results show that both growth factors elevate cell rigidity, size and migratory activity, however, effects of TGFβ stimulation on cell mechanical phenotype and differential gene expression turn out to be significantly stronger. Our microarray analysis reveals that TGFβ-treated NSCLC cells exhibit upregulation of migration-, adhesion-related and down- regulation of cytokinesis-related groups of genes. In addition to vimentin, a canonical marker of EMT, a large number of cytoskeletal and motor proteins including previously reported MYL9, MYLK, TMP1 but also less-known un- conventional myosins are overexpressed in lung adenocarcenoma cells upon treatment with TGFβ. Selective probing of gene-silenced cells lead to identi- fication of unconventional myosin MYH15 as a novel mediator of elevated cell rigidity and invasiveness in TGFβ-stimulated NSCLC cells. In comparison to TGFβ, HGF-treated NSCLC cells respond with upregulation of a relatively small number of genes that are related to actin cyskeleton, microtubules and caveolae. Our results provide insights into phenotypic effects and molecular mechanisms of TGFβ- and HGF-induced mesenchymal cell transformation in NSCLC, and suggest that mediators of cell mechanical enhancement such as unconventional cytoskeletal and motor proteins represent promising phar- maceutical targets for restraining invasive spread of lung cancer.
2019-12-26 | GSE98979 | GEO
Project description:RNA from patient samples was isolated to examine the TGFb pathway expression between matching pairs of tumor-free lung and NSCLC specimen RNA from patient samples was isolated to examine the TGFb pathway expression between matching pairs of tumor-free lung and NSCLC specimen
2016-05-18 | E-GEOD-74706 | biostudies-arrayexpress
Project description:Ischemia, fibrosis, and remodeling lead to heart failure after severe myocardial infarction (MI). Myoblast sheet transplantation is a promising therapy to enhance cardiac function and induce therapeutic angiogenesis via a paracrine mechanism in this detrimental disease. We hypothesized that in a rat model of MI-induced chronic heart failure this therapy could further be improved by overexpression of the antiapoptotic, antifibrotic, and proangiogenic hepatocyte growth factor (HGF) in the myoblast sheets. We studied the ability of wild type (L6-WT) and human HGF-expressing (L6-HGF) L6 myoblast sheet-derived paracrine factors to stimulate cardiomyocyte, endothelial cell, or smooth muscle cell migration in culture. Further, we studied the autocrine effect of hHGF-expression on myoblast gene expression using microarray analysis. We induced MI in Wistar rats by left anterior descending coronary artery (LAD) ligation and allowed heart failure to develop for four weeks. Thereafter, we administered L6-WT (n=15) or L6-HGF (n=16) myoblast sheet therapy. Control rats (n=13) underwent LAD ligation and rethoracotomy without therapy and five rats underwent sham-operation in both surgeries. We evaluated cardiac function with echocardiography at 2 and 4 weeks after therapy administration. We analyzed cardiac angiogenesis and left ventricular architecture from histological sections 4 weeks after therapy. Paracrine mediators from L6-HGF myoblast sheets effectively induced migration of cardiac endothelial and smooth muscle cells but not cardiomyocytes. Microarray data revealed that hHGF-expression modulated myoblast gene expression. In vivo, L6-HGF sheet therapy effectively stimulated angiogenesis in the infarcted and non-infarcted areas. Both L6-WT and L6-HGF therapies enhanced cardiac function and inhibited remodeling in a similar fashion. In conclusion, L6-HGF therapy effectively induced angiogenesis in the chronically failing heart. Cardiac function, however, was not further enhanced by hHGF-expression. Analysis of the L6 rat skeletal myoblast cell line and myoblast cell sheets with constitutive human HGF expression.
2010-12-10 | E-GEOD-25752 | biostudies-arrayexpress
Project description:Aberrant c-Met activation and upregulation of its cognate ligand HGF are frequently observed in bladder cancer and have been shown to regulate downstream pathways involved in proliferation, motility, and invasion. The precise mechanism underlying HGF/c-MET mediated invasion in bladder cancer is partly addressed by this microarray dataset. HGF activates the canonical TGFb signaling pathway to enhance epithelial mesenchymal transition and bladder carcinoma invasion.
2019-08-23 | GSE104740 | GEO
Project description:Gene expression profiling of NSCLC cell lines upon TGFb-induced epithelial-mesenchymal transition (EMT)
| PRJNA214591 | ENA
Project description:Ischemia, fibrosis, and remodeling lead to heart failure after severe myocardial infarction (MI). Myoblast sheet transplantation is a promising therapy to enhance cardiac function and induce therapeutic angiogenesis via a paracrine mechanism in this detrimental disease. We hypothesized that in a rat model of MI-induced chronic heart failure this therapy could further be improved by overexpression of the antiapoptotic, antifibrotic, and proangiogenic hepatocyte growth factor (HGF) in the myoblast sheets. We studied the ability of wild type (L6-WT) and human HGF-expressing (L6-HGF) L6 myoblast sheet-derived paracrine factors to stimulate cardiomyocyte, endothelial cell, or smooth muscle cell migration in culture. Further, we studied the autocrine effect of hHGF-expression on myoblast gene expression using microarray analysis. We induced MI in Wistar rats by left anterior descending coronary artery (LAD) ligation and allowed heart failure to develop for four weeks. Thereafter, we administered L6-WT (n=15) or L6-HGF (n=16) myoblast sheet therapy. Control rats (n=13) underwent LAD ligation and rethoracotomy without therapy and five rats underwent sham-operation in both surgeries. We evaluated cardiac function with echocardiography at 2 and 4 weeks after therapy administration. We analyzed cardiac angiogenesis and left ventricular architecture from histological sections 4 weeks after therapy. Paracrine mediators from L6-HGF myoblast sheets effectively induced migration of cardiac endothelial and smooth muscle cells but not cardiomyocytes. Microarray data revealed that hHGF-expression modulated myoblast gene expression. In vivo, L6-HGF sheet therapy effectively stimulated angiogenesis in the infarcted and non-infarcted areas. Both L6-WT and L6-HGF therapies enhanced cardiac function and inhibited remodeling in a similar fashion. In conclusion, L6-HGF therapy effectively induced angiogenesis in the chronically failing heart. Cardiac function, however, was not further enhanced by hHGF-expression.
2010-12-10 | GSE25752 | GEO
Project description:Therapeutic resistance to VEGFR signaling inhibitors is a major obstacle in the treatment of non-small cell lung cancer (NSCLC). We investigated the contribution of stromal and tumor cells to resistance of NSCLC to VEGFR tyrosine kinase inhibitors (TKIs). Gene expression analysis of stromal (mouse) and tumor (human) compartments enabled us to identify the HGF/c-MET pathway as a driver and a potential biomarker of VEGFR TKI resistance.
2017-07-06 | GSE64472 | GEO
Project description:RNA from patient samples was isolated to examine the TGFb pathway expression between matching pairs of tumor-free lung and NSCLC specimen
2016-05-18 | GSE74706 | GEO
Project description:MET exon 14 skipping alteration (MET∆14Ex) is an actionable oncogenic driver that occurs in 2-4% of non-small cell lung cancer (NSCLC) cases. However, the precise role of MET∆14Ex in tumor progression in NSCLC is poorly understood. We here demonstrate that MET∆14Ex expression increases receptor kinase activity and downstream signaling by impairing receptor internalization and endocytic degradation, which significantly boosts tumor cell scattering and invasion as well as metastasis. To explore the key mechanisms in regulation of these phenotypes, RNA sequencing (RNA-seq) studies were conducted on HGF-treated MET∆14Ex and MET cell models in an effort to identify the global change of transcriptome signature and key functional pathways involved in MET∆14Ex-medieated tumorigenesis. Both Ingenuity pathway analysis (IPA) and gene set enrichment analysis (GSEA) revealed an induction of a tight cluster of functional pathways associated with cell movement in HGF-treated MET∆14Ex models (vs MET) in a time-dependent manner.
2021-12-31 | GSE182684 | GEO
Project description:We report the high-throughput profiling of HGF treated liver cancer cell (HepG2) for differentiated genes analysis. We generated HGF stimulated and paired control HepG2 cells for 4 days. We find that tumor suppressor genes that are overexpressed and some tumor associated genes were downregulated, therefore reflect cell state and HGF induced anti-tumor potential. This study provides a potential framework for the research of HGF induced critical genes in the application of liver cancer therapy.
2021-12-30 | GSE133424 | GEO