Fenbendazole Met ID_in vitro_cross-species_FBMN
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Q Exactive
ORGANISM(S): Canis Lupus Familiaris (ncbitaxon:9615) Macaca Fascicularis (ncbitaxon:9541) Cd1 Mouse Homo Sapiens (ncbitaxon:9606)
SUBMITTER: 
Ju-Hyun Kim
PROVIDER: MSV000095554 | MassIVE | Thu Aug 08 01:45:00 BST 2024
REPOSITORIES: MassIVE
Similar Datasets
Project description:Chronic liver diseases are worldwide on the rise. Due to the rapidly increasing incidence, in particular in Western countries, non-alcoholic fatty liver disease (NAFLD) is gaining importance. As the disease progresses it can develop into hepatocellular carcinoma. Lipid accumulation in hepatocytes has been identified as the characteristic structural change in NAFLD development, but the molecular mechanisms responsible for disease development remained unresolved. Here, we uncover a strong downregulation of the PI3K-AKT pathway and an upregulation of the MAPK pathway in primary hepatocytes from a preclinical model fed with a Western diet (WD). Dynamic pathway modeling of hepatocyte growth factor (HGF) signal transduction combined with global proteomics identifies that an elevated basal MET phosphorylation rate is the main driver of altered signaling leading to increased proliferation of WD-hepatocytes. Model-adaptation to patient-derived hepatocytes reveals a patient-specific variability in basal MET phosphorylation, which correlates with the outcome of patients after liver surgery. Thus, dysregulated basal MET phosphorylation could be an indicator for the health status of the liver and thereby inform on the risk of a patient to suffer from liver failure after surgery.
2025-03-24 | BIOMD0000001102 | BioModels
Project description:We analyzed the molecular changes in a mouse c-MET over-expression model of hepatocellular carcinoma (HCC). FVB mice overexpressing human c-MET carried one copy of the LAP-tTa transgene (the liver-specific LAP promoter driving the Tet-VP16 transactivator) and one copy of the TRE-c-MET transgene (Tet-operator regulated human c-MET gene). Normal liver or liver tumor tissue (two per mouse) was collected and processed for gene expression profiling.
2011-08-14 | E-GEOD-25142 | biostudies-arrayexpress
Project description:Non-alcoholic fatty liver disease (NAFLD) is gaining evermore importance due to rapidly rising incidence rates especially in western countries. As the disease progresses, it can develop into hepatocellular carcinoma. Related metabolic changes have been extensively studied in the past. However, the molecular mechanisms responsible for the development of fatty liver disease remain uncovered. Here we show that the basal phosphorylation of the MET receptor can be used as an indicator for hepatocyte dysregulation in fatty liver disease. Using primary hepatocytes isolated from a preclinical model fed with high-fat, high-sugar diet (Western diet; WD) or standard diet (SD), we find a strong downregulation of the PI3K-AKT pathway and upregulation of the MAPK pathway in the WD derived hepatocytes. By developing a mathematical model of HGF-induced signal transduction, calibrated with quantitative time-resolved measurements of both PI3K-AKT and MAPK pathways, we resolve molecular mechanisms responsible for these alterations. Thereby, we identify the basal MET phosphorylation rate as main driver for the altered signal transduction in WD hepatocytes that even leads to an increased proliferation behavior of the usually quiescent hepatocytes in the absence of growth factors. The adaptation of the dynamic pathway model of HGF signal transduction to patient-derived hepatocytes reveals a patient-specific variability of basal MET phosphorylation levels, which correlates with the clinical outcome of patients after liver surgery. These findings suggest that the dysregulated basal MET phosphorylation could be exploited to assess the health status of the liver and thereby inform estimation of the risk of a patient to suffer from liver failure after surgery.Non-alcoholic fatty liver disease (NAFLD) is gaining evermore importance due to rapidly rising incidence rates especially in western countries. As the disease progresses, it can develop into hepatocellular carcinoma. Related metabolic changes have been extensively studied in the past. However, the molecular mechanisms responsible for the development of fatty liver disease remain uncovered. Here we show that the basal phosphorylation of the MET receptor can be used as an indicator for hepatocyte dysregulation in fatty liver disease. Using primary hepatocytes isolated from a preclinical model fed with high-fat, high-sugar diet (Western diet; WD) or standard diet (SD), we find a strong downregulation of the PI3K-AKT pathway and upregulation of the MAPK pathway in the WD derived hepatocytes. By developing a mathematical model of HGF-induced signal transduction, calibrated with quantitative time-resolved measurements of both PI3K-AKT and MAPK pathways, we resolve molecular mechanisms responsible for these alterations. Thereby, we identify the basal MET phosphorylation rate as main driver for the altered signal transduction in WD hepatocytes that even leads to an increased proliferation behavior of the usually quiescent hepatocytes in the absence of growth factors. The adaptation of the dynamic pathway model of HGF signal transduction to patient-derived hepatocytes reveals a patient-specific variability of basal MET phosphorylation levels, which correlates with the clinical outcome of patients after liver surgery. These findings suggest that the dysregulated basal MET phosphorylation could be exploited to assess the health status of the liver and thereby inform estimation of the risk of a patient to suffer from liver failure after surgery.
2024-01-15 | PXD043007 | Pride
Project description:We profiled the mutations and gene expressions of early and advanced hepatocellular carcinoma (HCC) related with Hepatitis B-viral infection. Integrative analysis was performed with whole-exome sequencing and gene expression profiles of the 12 cases of early and advanced HCCs and paired non-tumoral adjacent liver tissues. 12 HCC Samples
2014-10-19 | E-GEOD-62441 | biostudies-arrayexpress
Project description:Non-alcoholic fatty liver disease (NAFLD) is gaining evermore importance due to rapidly rising incidence rates especially in western countries. As the disease progresses, it can develop into hepatocellular carcinoma. Related metabolic changes have been extensively studied in the past. However, the molecular mechanisms responsible for the development of fatty liver disease remain uncovered. Here we show that the basal phosphorylation of the MET receptor can be used as an indicator for hepatocyte dysregulation in fatty liver disease. Using primary hepatocytes isolated from a preclinical model fed with high-fat, high-sugar diet (Western diet; WD) or standard diet (SD), we find a strong downregulation of the PI3K-AKT pathway and upregulation of the MAPK pathway in the WD derived hepatocytes. By developing a mathematical model of HGF-induced signal transduction, calibrated with quantitative time-resolved measurements of both PI3K-AKT and MAPK pathways, we resolve molecular mechanisms responsible for these alterations. Thereby, we identify the basal MET phosphorylation rate as main driver for the altered signal transduction in WD hepatocytes that even leads to an increased proliferation behavior of the usually quiescent hepatocytes in the absence of growth factors. The adaptation of the dynamic pathway model of HGF signal transduction to patient-derived hepatocytes reveals a patient-specific variability of basal MET phosphorylation levels, which correlates with the clinical outcome of patients after liver surgery. These findings suggest that the dysregulated basal MET phosphorylation could be exploited to assess the health status of the liver and thereby inform estimation of the risk of a patient to suffer from liver failure after surgery.
2024-01-15 | PXD041563 | Pride
Project description:Regulation of embryonic liver growth remains largely elusive. Progranulin has been discussed in pathological liver growth; however, the functional role of Pgrn in embryonic liver growth has never been addressed. Knockdown of GrnA, the orthologue of mammalian pgrn in zebrafish, displayed a deficient hepatic outgrowth during hepatogenesis. Expression profiles manifested that pgrn-deficiency impaired hepatogenesis associated with dysregulation of Met signaling. Pgrn regulates hepatic expression of Met was further verified in vitro and in vivo. These results indicate that Pgrn is a novel factor required for embryonic hepatic outgrowth and reveal a novel link between Pgrn and Met signaling.
2010-11-10 | GSE19211 | GEO
Project description:Hepatocyte growth factor (HGF) signaling through its receptor Met has been implicated in hepatocellular carcinoma tumorigenesis and progression. Met interaction with integrins is shown to modulate the downstream signaling to Akt and ERK (extracellular-regulated kinase). In this study, we developed a mechanistically detailed systems biology model of HGF/Met signaling pathway that incorporated specific interactions with integrins to investigate the efficacy of integrin-binding peptide, AXT050, as monotherapy and in combination with other therapeutics targeting this pathway. Here we report that the modeled dynamics of the response to AXT050 revealed that receptor trafficking is sufficient to explain the effect of Met-integrin interactions on HGF signaling. Furthermore, the model predicted patient-specific synergy and antagonism of efficacy and potency for combination of AXT050 with sorafenib, cabozantinib, and rilotumumab. Overall, the model provides a valuable framework for studying the efficacy of drugs targeting receptor tyrosine kinase interaction with integrins, and identification of synergistic drug combinations for the patients.
Model is encoded by Johannes and submitted to BioModels by Ahmad Zyoud.
2020-03-20 | MODEL2003200001 | BioModels
Project description:This SuperSeries is composed of the following subset Series: GSE35311: Integrative array-based approach identifies MZB1 as a frequently methylated putative tumor-suppressor in hepatocellular carcinoma (expression) GSE35312: Integrative array-based approach identifies MZB1 as a frequently methylated putative tumor-suppressor in hepatocellular carcinoma (MeDIP) Refer to individual Series
2012-03-30 | E-GEOD-35313 | biostudies-arrayexpress
Project description:We profiled the mutations and gene expressions of early and advanced hepatocellular carcinoma (HCC) related with Hepatitis B-viral infection. Integrative analysis was performed with whole-exome sequencing and gene expression profiles of the 12 cases of early and advanced HCCs and paired non-tumoral adjacent liver tissues.
2014-10-19 | GSE62441 | GEO
Project description:This SuperSeries is composed of the following subset Series:; GSE11440: Role of Caveolin 1, E-Cadherin, Enolase 2 and PKCa on resistance to methotrexate in human HT29 colon cancer cells; GSE16066: Networking of differentially expressed genes in CaCo2 human colon cancer cells resistant to methotrexate; GSE16070: Networking of differentially expressed genes in human MCF7 breast cancer cells resistant to methotrexate; GSE16080: Networking of differentially expressed genes in human MDA-MB-468 breast cancer cells resistant to methotrexate; GSE16082: Networking of differentially expressed genes in human MIA PaCa2 pancreatic cancer cells resistant to methotrexate; GSE16085: Networking of differentially expressed genes in human K562 erythtoblastic leukemia cells resistant to methotrexate; GSE16089: Networking of differentially expressed genes in human Saos-2 osteosarcoma cells resistant to methotrexate Experiment Overall Design: Refer to individual Series
2009-09-11 | E-GEOD-16648 | biostudies-arrayexpress