Similar Datasets
Project description:Control (cMet+ T cells less than 0.5%) and cMet-enriched (7%) T cells were activated with plate-bound anti-CD3/CD28 and gene tracription was measured
2022-09-15 | GSE186270 | GEO
Project description:cMET is a well known oncogene whose activation is widely implicated in tumorigenesis and metastasis. To investigate the effects of acute inhibitoin of cMET signaling in the mammary tumors, we inhibited cMET activation in xenograft mammary tumors that were derived from a MET amplified mouse mammary tumor cell line and analyzed the transcriptional alteration between vehicle and MET inhibitor treated tumors.
2020-02-23 | GSE52097 | GEO
Project description:Neurofibromatosis type II (NF2) is a disease that needs new solutions. Vestibular schwannoma (VS) growth cause progressive hearing loss, and the standard treatment including surgery and radiotherapy, can further damage the nerve. There is an urgent need to identify an adjunct therapy that, by enhancing the efficacy of radiation, can help lower the radiation dose and preserve hearing. The mechanisms underlying deafness in NF2 are still unclear. One of the major limitations in studying tumor-induced hearing loss is the lack of mouse models that allows hearing test. Here we developed a cerebellopontine angle (CPA) schwannomas model that faithfully recapitulates the tumor-induced hearing loss. Using this model we discovered that cMET blockade by crizotinib (CRZ) enhanced schwannoma radiosensitivity by enhancing DNA damage, and CRZ treatment combined with low-dose radiation was as effective as high-dose radiation. CRZ treatment had no adverse effect on hearing; however, it did not affect tumor-induced hearing loss, presumably because cMET blockade did not change tumor HGF levels. cMET gene knockdown study independently confirmed the role of cMET pathway in mediating the effect of CRZ. Furthermore, we evaluated the translational potential of cMET blockade in human schwannomas. We found that human NF2-associated and sporadic VSs showed significantly elevated HGF expression and cMET activation compared to normal nerves, which correlated with tumor growth and cyst formation. Using organoid brain slice culture, cMET blockade inhibited the growth of patient-derived schwannomas. Our findings provide the rationale and necessary data for the clinical translation of combined cMET blockade with radiation therapy in NF2 patients. We found that human NF2-associated and sporadic VSs showed significantly elevated HGF expression and cMET activation compared to normal nerves, which correlated with tumor growth and cyst formation.
2018-06-26 | GSE108524 | GEO
Project description:cMET is a well known oncogene whose activation is widely implicated in tumorigenesis and metastasis. To investigate the effects of acute activation of cMET signaling in the mammary epithelial cells, we stimulated MCF10A cells with increasing doses of HGF and analyzed the transcriptional alteration between PBS and HGF treated cells.
2020-02-23 | GSE52096 | GEO
Project description:DU145 prostate cancer cells were treated with 25 ng/ml hepatocyte growth factor (HGF) or vehicle for 2, 8, or 24 hours. HGF stimulates the cMET protein, a tyrosine kinase transmembrane protein. The aim of this study is to determine the role of the HGF/cMET pathway in immature cells of established prostate cancer. HGF stimulation of DU145 prostate cancer cell line led to cell migration in culture, formation of sprouts in Matrigel and inhibition of growth. These biological effects went together with induction of a stem-like phenotype as defined by up-regulation of CD49b, CD49f, CD44 and SOX9, and down-regulation of CD24 on gene-expression arrays and quantitative PCR. The shift towards a stem-like phenotype was reflected by protein modifications on FACS, Western blot, and enhanced rapid adhesion to collagen I. Small molecules SU11274 and PHA665752 were able to inhibit both morphologic and molecular HGF effects.
2011-12-16 | GSE16659 | GEO
Project description:Study of gene expression of mouse cMET experiments
| PRJNA134481 | ENA
Project description:Differential gene expressionin cMet-enriched T cell populations
| PRJNA773097 | ENA
Project description:HNF4α is a transcription factor that plays a critical role in terminal hepatocyte failure. HNF4α-based reprogramming therapy can correct terminal liver failure in rats and humans. As liver disease progresses, HNF4α expression decreases in the nuclei of hepatocytes, leading to impaired regulation and hepatic function. Post-translational modifications (PTMs) are a fundamental regulatory mechanism of protein function and localization. In this study, we analyzed HNF4α localization and pathways involved in HNF4α PTMs in human hepatocytes at different stages of decompensated liver function upon Child-Pugh classification. RNA-seq analysis revealed that HNF4α and the PTMs-pathway related to AKT are down-regulation in cirrhotic hepatocytes with terminal failure. These findings were confirmed by protein expression, where the HNF4α nuclear levels are significantly reduced in Child‐Pugh B and C hepatocytes, whereas cytoplasmic expression of HNF4α was increased. Moreover, cMET and phospho-AKT were significantly reduced in Child‐Pugh B and C hepatocytes. The association and statistical contribution of cMET and phospho-AKT to the nuclear localization of HNF4α were confirmed by Spearman’s rank correlation test and pathway analysis. Principal component analysis was used to characterize the protein profiles related to the degree of liver dysfunction. Additionally, HNF4α acetylation was significantly reduced in failing human hepatocytes when compared to normal controls, demonstrating a significant correlation to the degree of hepatic function. Conclusion: These results suggest that the alterations in the cMET-AKT pathway directly correlate to HNF4α localization and the level of hepatic dysfunction. In conclusion, this study has therapeutic implications and suggests that manipulation of these pathways may restore hepatocyte function in terminal liver failure.
2020-03-19 | GSE134422 | GEO
Project description:DU145 prostate cancer cells were treated with 25 ng/ml hepatocyte growth factor (HGF) or vehicle for 2, 8, or 24 hours. HGF stimulates the cMET protein, a tyrosine kinase transmembrane protein. The aim of this study is to determine the role of the HGF/cMET pathway in immature cells of established prostate cancer. HGF stimulation of DU145 prostate cancer cell line led to cell migration in culture, formation of sprouts in Matrigel and inhibition of growth. These biological effects went together with induction of a stem-like phenotype as defined by up-regulation of CD49b, CD49f, CD44 and SOX9, and down-regulation of CD24 on gene-expression arrays and quantitative PCR. The shift towards a stem-like phenotype was reflected by protein modifications on FACS, Western blot, and enhanced rapid adhesion to collagen I. Small molecules SU11274 and PHA665752 were able to inhibit both morphologic and molecular HGF effects. DU145 cells were stimulated for 2, 8 and 24 hours with 25 ng/ml HGF or vehicle. For each time point two arrays analyses were performed. One for cells stimulated with a vehicle and one for the HGF stimulated cells. Six arrays were performed in total in this study.
2011-12-16 | E-GEOD-16659 | biostudies-arrayexpress
Project description:Gene expression in Madin Darby canine kidney cells grown for 7 days to confluence on Transwell filters and exposed to HGF +/- inhibitors of the MAPK pathway (MAPK is one of the pathways activated when HGF binds to the CMET receptor tyrosine kinase). We used microarrays to detail the program of gene expression in MDCK cells and identified genes specifically regulated by HGF via the MAPK pathway. Keywords: signaling pathway analysis
2007-11-20 | GSE9435 | GEO