{"database":"Cell Collective","file_versions":[],"scores":null,"additional":{"omics_type":["Models","Multiomics"],"submitter":["Tomas Helikar"],"version_name":[""],"full_dataset_link":["https://cellcollective.org/#1969/hgf-signaling-in-keratinocytes"],"model_score":["6.999999999999999"],"default_version":["1"],"ModelFormat":["SBML"],"submitter_affiliation":[""],"submitter_email":[""],"version_id":["1"],"repository":["Cell Collective"],"version_url":["https://cellcollective.org/#1969:1/hgf-signaling-in-keratinocytes"],"version_description":[""],"pubmed_abstract":["<h4>Motivation</h4>Cell migration is a complex process that is controlled through the time-sequential feedback regulation of protein signalling and gene regulation. Based on prior knowledge and own experimental data, we developed a large-scale dynamic network describing the onset and maintenance of hepatocyte growth factor-induced migration of primary human keratinocytes. We applied Boolean logic to capture the qualitative behaviour as well as short-and long-term dynamics of the complex signalling network involved in this process, comprising protein signalling, gene regulation and autocrine feedback.<h4>Results</h4>A Boolean model has been compiled from time-resolved transcriptome data and literature mining, incorporating the main pathways involved in migration from initial stimulation to phenotype progress. Steady-state analysis under different inhibition and stimulation conditions of known key molecules reproduces existing data and predicts novel interactions based on our own experiments. Model simulations highlight for the first time the necessity of a temporal sequence of initial, transient MET receptor (met proto-oncogene, hepatocyte growth factor receptor) and subsequent, continuous epidermal growth factor/integrin signalling to trigger and sustain migration by autocrine signalling that is integrated through the Focal adhesion kinase protein. We predicted in silico and verified in vitro that long-term cell migration is stopped if any of the two feedback loops are inhibited.<h4>Availability</h4>The network file for analysis with the R BoolNet library is available in the Supplementary Information.<h4>Contact</h4>melanie.boerries@frias.uni-freiburg.de or hauke.busch@frias.uni-freiburg.de<h4>Supplementary information</h4>Supplementary data are available at Bioinformatics online."],"pubmed_title":["Boolean approach to signalling pathway modelling in HGF-induced keratinocyte migration."],"pubmed_authors":["Singh Amit A, Nascimento Juliana M JM, Kowar Silke S, Busch Hauke H, Boerries Melanie M"],"description_synonyms":["Focal Adhesion, scale tissue, Library., Materials, E 920, Hgfr, alphaPS2, determination, Mbp1, Gene Expression Profile, 5730555F13Rik, TGF-alpha receptor binding, Hepatocyte, Hepatopoietin A, protein, Profiles, Adherens Junctions, Long Term, Social Controls, temporal, ter, Methionine, HGFR, Human Urinary Gastric Inhibitor, 2-amino-3-mercaptopropanoic acid, Cystein, Kinase, alpha2Int, Focal Contact, Cell Motility, protein aggregate, myd, Effect, Formal Social Controls, IKKg, KEY, Key, adhesion plaque, C, hemi-adherens junction, Man (Taxonomy), Migrant Worker, reference sample, MUB3_18, Focal, availability, cisteina, M, Cell-Matrix Adherens Junctions, plant peltate hair, long, Nonmigrant, Cell Locomotion, Mbp-1, Age of onset, Growth Factor-Urogastrone, MUB3.18, Transient, Signatures, Social, Adhesions, Movements, transforming growth factor alpha receptor binding, DmelCG9623, Expression Signature, Bsg75C, signaling process, Adhesion, Transcriptomes, Squatters, Locomotion, Adherens Junction, Contacts, RG7MT1, Adhesion Plaques, ATP Phosphotransferases, Racemethionine, Adhesion Plaque, Long-Term Effects, ATP, single organism signaling, single-organism behavior, Plaque, Motility, proto-oncogene c-Met, anatomical protrusion, gyltl1b-b, PRO, PS2, Focal Contacts, Modern, Cell Migration, Expression Profiles, 2-Amino-4-(methylthio)butyric acid, Cell-Matrix, Longterm Effect, 9130215G10Rik, CYS, Cys, results, predicted, Literatures, shortened, Gene Expression, aPS2, DmIKKgamma, CT27194, Cell-Matrix Adherens Junction, Term, dIKK, MDDGA6, mKIAA0609, Expression Signatures, Migrant, beta Urogastrone, Kenny, Genetic Materials, Methionin, Workers, methionine, Hmet, KIAA0609, (2R)-2-amino-3-sulfanylpropanoic acid, Expression Profile, and GLY protein 2, Urogastrone, Genetic Material, Migrants and Transients, Transcriptome Profiles, HGF receptor, HGF/SF receptor, fg, Transphosphorylases, Epistemology, and GLY protein 1, gyltl1b, mdc1d, IKK-gamma, Control, expanded, Epidermal growth factor, CG9623, INSDC_feature:gene, scatter factor, hCMT1c, Controls, c-Met, Junction, Cell-Matrix Adherens, human, L-Cystein, Plaques, experimental procedures, Scatter Factor, Phenotypes, MDC1D, DmelCG16910, enr, enlarged, spine, Material, Cistron, Migrants, Feedbacks, PSalpha2, short, Regulation, TGFalpha receptor binding, Regulations, big, biological signaling, EGF receptor binding, Migration, human being, 2-amino-4-(methylsulfanyl)butanoic acid, Logics, experimental, Effects, Transcriptome Profile, peltate hair, L-Zystein, Integrin, Gene, protein-containing complex, dIKK-gamma, Migrant Workers, froggy, Gyltl1a, protrusion, Human, large, beta-Urogastrone, in, HGF, Homo sapiens, DmIKK-gamma, Gene Products, F15E12.6, Growth Factor, dmIKKgamma, RCCP2, IKK[[gamma]], Man, Phosphotransferase, epidermal growth factor, If, HGF receptor binding, F15E12_6, transforming growth factor alpha receptor ligand, methods, Genetic, alpha[[PS2]], Longterm, epidermal growth factor receptor ligand, scatter factor receptor, experimental section, MDDGB6, Profile, E-920, Transients, EGFR binding, stubby, HPTA, Nonmigrants, LARGE, Hcys, Long-Term, Transphosphorylase, Worker, Maintenances, integrin, AUTS9, Junctions, Cell Movements, focal contact, Lymphokines and Cytokines, Squatter, BPFD#36, Movement, Epidermal Growth Factor-Urogastrone, DmelCG4216, 2-amino-4-(methylthio)butanoic acid, IKK, CYSTEINE, Met proto-oncogene, alphaPS2C, great, EGF receptor ligand, PS 2, FREE CYSTEINE, Long-Term Effect, AI838057, (2R)-2-amino-3-mercaptopropanoic acid, metionina, Hepatocyte Growth, incidence, Controlled, Controlling, RCG27969, Transcriptome, hepatocyte growth factor receptor ligand, pro-epidermal growth factor, Formal Social Control, DL-Methionine, protein complex, Proteins, Factor, Cistrons, Cell, Phosphotransferases, whole transcriptome, IKKgamma, transforming growth factor alpha, native protein, Social Control, Long Term Effects, Protein, Gene Expression Signatures, chemical analysis, Nomad, sequence, Gene Expression Signature, scales, Scatter, Zystein, Met, MET, ATCMPG1, ATCMPG2, Cell Matrix Adherens Junctions, scale, Dmikkgamma, 2-amino-3-sulfanylpropanoic acid, Kinases, tyrosine-protein kinase Met, CG4216, L-2-Amino-3-mercaptopropionic acid, hepatocyte growth factor, (R)-2-amino-3-mercaptopropanoic acid, Age symptoms begin, Keratinocyte, CG16910, primary structure of sequence macromolecule, 2-Amino-3-mercaptopropionic acid, Longterm Effects, signalling, Protein Gene Products, inf, Gene Proteins, EGF, Hepatopoietin, signalling process, Epidermal, Gene Expression Profiles, Modern Man, Nomads, Contact, alpha-amino-gamma-methylmercaptobutyric acid, PS2alpha, E920, alpha[[PS2(ms8)]], regulation, assay, Par4, Signature, 5730455C01Rik, SF receptor, autocrine signalling"],"pubmed_title_synonyms":["signal transduction by protein phosphorylation, F-TCF, GINGF, SF|HGF, NS4, signal transduction by conformational transition, SF, HPTA, DFNB39, NK2, NK1, HSF, HGFB, c-Met, signal transduction by trans-phosphorylation, HGF/SF, BSF2, signaling cascade, signalling pathway, IFNB2, HGF, signaling pathway, C230052L06Rik, GGF1, HGFR, IL-6, Human Gingival Fibroblasts, HGF|SF, signal transduction by cis-phosphorylation, GF1, SF/HGF., Par4, AI838057, signalling cascade"],"name_synonyms":["F-TCF, GINGF, SF|HGF, NS4, SF, HPTA, DFNB39, NK2, NK1, HSF, HGFB, c-Met, HGF/SF, BSF2, IFNB2, HGF, C230052L06Rik, signalling process, GGF1, HGFR, Keratinocyte., IL-6, Human Gingival Fibroblasts, HGF|SF, GF1, Par4, AI838057, SF/HGF, single organism signaling"],"pubmed_abstract_synonyms":["Focal Adhesion, scale tissue, Library., E 920, Hgfr, alphaPS2, determination, Mbp1, Gene Expression Profile, 5730555F13Rik, TGF-alpha receptor binding, Hepatocyte, Hepatopoietin A, protein, Profiles, neutral molecular compounds, Adherens Junctions, Long Term, Social Controls, temporal, ter, Methionine, HGFR, Human Urinary Gastric Inhibitor, 2-amino-3-mercaptopropanoic acid, Cystein, alpha2Int, Focal Contact, Cell Motility, protein aggregate, myd, Effect, Formal Social Controls, molecule, IKKg, KEY, Key, molecula, adhesion plaque, C, hemi-adherens junction, molecules, Man (Taxonomy), Migrant Worker, reference sample, MUB3_18, Focal, availability, cisteina, M, Cell-Matrix Adherens Junctions, plant peltate hair, long, Nonmigrant, Cell Locomotion, Mbp-1, Age of onset, Growth Factor-Urogastrone, Molekuel, MUB3.18, Transient, Signatures, Social, Adhesions, Movements, transforming growth factor alpha receptor binding, DmelCG9623, Expression Signature, Bsg75C, signaling process, Adhesion, Transcriptomes, Squatters, Locomotion, Adherens Junction, Contacts, RG7MT1, Adhesion Plaques, Racemethionine, Adhesion Plaque, Long-Term Effects, single organism signaling, single-organism behavior, Plaque, Motility, proto-oncogene c-Met, anatomical protrusion, gyltl1b-b, PRO, PS2, Focal Contacts, Modern, Cell Migration, Expression Profiles, 2-Amino-4-(methylthio)butyric acid, Cell-Matrix, Longterm Effect, 9130215G10Rik, CYS, Cys, results, predicted, Incentive, Literatures, shortened, Gene Expression, aPS2, DmIKKgamma, CT27194, Cell-Matrix Adherens Junction, Term, dIKK, MDDGA6, mKIAA0609, Expression Signatures, Migrant, beta Urogastrone, Kenny, Methionin, Workers, methionine, Hmet, KIAA0609, (2R)-2-amino-3-sulfanylpropanoic acid, Expression Profile, and GLY protein 2, Urogastrone, Migrants and Transients, Transcriptome Profiles, HGF receptor, HGF/SF receptor, fg, Epistemology, and GLY protein 1, gyltl1b, Disincentive, mdc1d, IKK-gamma, Control, expanded, Epidermal growth factor, CG9623, scatter factor, hCMT1c, Controls, c-Met, Junction, Cell-Matrix Adherens, human, regulation of protein expression, L-Cystein, Plaques, Scatter Factor, Phenotypes, MDC1D, DmelCG16910, enr, enlarged, spine, Migrants, Feedbacks, PSalpha2, short, Regulation, TGFalpha receptor binding, Regulations, big, Incentives, biological signaling, EGF receptor binding, Migration, human being, 2-amino-4-(methylsulfanyl)butanoic acid, Logics, Effects, Transcriptome Profile, peltate hair, L-Zystein, Integrin, Gene, protein-containing complex, dIKK-gamma, Migrant Workers, regulation of gene product expression, froggy, Gyltl1a, protrusion, Human, large, beta-Urogastrone, in, HGF, Homo sapiens, DmIKK-gamma, Gene Products, F15E12.6, Growth Factor, dmIKKgamma, RCCP2, IKK[[gamma]], Man, epidermal growth factor, If, HGF receptor binding, F15E12_6, Motivations, transforming growth factor alpha receptor ligand, alpha[[PS2]], Longterm, epidermal growth factor receptor ligand, scatter factor receptor, MDDGB6, Profile, E-920, Transients, EGFR binding, stubby, HPTA, Nonmigrants, LARGE, Hcys, Long-Term, Worker, Maintenances, integrin, AUTS9, Junctions, Cell Movements, focal contact, Lymphokines and Cytokines, Squatter, BPFD#36, Movement, Epidermal Growth Factor-Urogastrone, DmelCG4216, 2-amino-4-(methylthio)butanoic acid, IKK, CYSTEINE, Met proto-oncogene, alphaPS2C, great, EGF receptor ligand, PS 2, FREE CYSTEINE, Long-Term Effect, Disincentives, AI838057, (2R)-2-amino-3-mercaptopropanoic acid, metionina, Hepatocyte Growth, incidence, Controlled, Controlling, RCG27969, Transcriptome, hepatocyte growth factor receptor ligand, pro-epidermal growth factor, Formal Social Control, DL-Methionine, protein complex, Proteins, Factor, Cell, whole transcriptome, IKKgamma, transforming growth factor alpha, native protein, Social Control, Long Term Effects, Protein, Gene Expression Signatures, chemical analysis, Nomad, sequence, gene regulation, Gene Expression Signature, scales, Scatter, Zystein, Met, MET, ATCMPG1, ATCMPG2, Cell Matrix Adherens Junctions, scale, Dmikkgamma, 2-amino-3-sulfanylpropanoic acid, tyrosine-protein kinase Met, CG4216, L-2-Amino-3-mercaptopropionic acid, hepatocyte growth factor, (R)-2-amino-3-mercaptopropanoic acid, Age symptoms begin, Keratinocyte, CG16910, primary structure of sequence macromolecule, 2-Amino-3-mercaptopropionic acid, Longterm Effects, signalling, Protein Gene Products, inf, Gene Proteins, EGF, Hepatopoietin, signalling process, Epidermal, Gene Expression Profiles, Modern Man, Nomads, Contact, alpha-amino-gamma-methylmercaptobutyric acid, PS2alpha, E920, alpha[[PS2(ms8)]], regulation, assay, Par4, Signature, 5730455C01Rik, SF receptor, autocrine signalling"],"additional_accession":[]},"is_claimable":false,"name":"HGF Signaling in Keratinocytes","description":"Cell migration is a complex process that is controlled through the time-sequential feedback regulation of protein signalling and gene regulation. Based on prior knowledge and own experimental data, we developed a large-scale dynamic network describing the onset and maintenance of hepatocyte growth factor-induced migration of primary human keratinocytes. We applied Boolean logic to capture the qualitative behaviour as well as short-and long-term dynamics of the complex signalling network involved in this process, comprising protein signalling, gene regulation and autocrine feedback. RESULTS: A Boolean model has been compiled from time-resolved transcriptome data and literature mining, incorporating the main pathways involved in migration from initial stimulation to phenotype progress. Steady-state analysis under different inhibition and stimulation conditions of known key molecules reproduces existing data and predicts novel interactions based on our own experiments. Model simulations highlight for the first time the necessity of a temporal sequence of initial, transient MET receptor (met proto-oncogene, hepatocyte growth factor receptor) and subsequent, continuous epidermal growth factor/integrin signalling to trigger and sustain migration by autocrine signalling that is integrated through the Focal adhesion kinase protein. We predicted in silico and verified in vitro that long-term cell migration is stopped if any of the two feedback loops are inhibited. AVAILABILITY: The network file for analysis with the R BoolNet library is available in the Supplementary Information. CONTACT: melanie.boerries@frias.uni-freiburg.de or hauke.busch@frias.uni-freiburg.de","dates":{"created":"2012-09-12","publication":"","submission":"2017-07-12","last_modified":"2017-07-12"},"accession":"1969","cross_references":{"pubmed":["22962472"]}}