{"database":"BioModels","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Pdf":["https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000453?filename=BIOMD0000000453.pdf"],"Owl":["https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000453?filename=BIOMD0000000453-biopax2.owl","https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000453?filename=BIOMD0000000453-biopax3.owl"],"Svg":["https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000453?filename=BIOMD0000000453.svg"],"Xml":["https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000453?filename=BIOMD0000000453_url.xml","https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000453?filename=BIOMD0000000453_urn.xml"],"Other":["https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000453?filename=BIOMD0000000453.m","https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000453?filename=BIOMD0000000453.xpp","https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000453?filename=BIOMD0000000453.vcml","https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000453?filename=BIOMD0000000453.sci","https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000453?filename=BIOMD0000000453.png"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"submitter":["Gholamreza Bidkhori"],"curationStatus":["Manually curated"],"modellingApproach":["ordinary differential equation model"],"disease":["Non-small Cell Lung Carcinoma"],"levelVersion":["L2V4"],"full_dataset_link":["https://www.ebi.ac.uk/biomodels/BIOMD0000000453"],"publication_pubmed":["23133538"],"isPrivate":["false"],"repository":["BioModels"],"non_derived_xrefs":["BIOMD0000000093 biomodels.db BIOMD0000000048 biomodels.db BIOMD0000000049 biomodels.db BIOMD0000000094 biomodels.db BIOMD0000000205 biomodels.db BIOMD0000000019 biomodels.db BIOMD0000000009 biomodels.db"],"omics_type":["Models"],"modelFormat":["SBML"],"tokenised_name":["Bidkhori2012 EGFR signalling in NSCLC"],"publication_year":["2012"],"submissionId":["MODEL1304020001"],"publication_authors":["Bidkhori G, Moeini A, Masoudi-Nejad A"],"first_author":["Bidkhori G"],"publication":["23133538,\n EGFR signaling plays a very important role in NSCLC. It activates Ras/ERK, PI3K/Akt and STAT activation pathways. These are the main pathways for cell proliferation and survival. We have developed two mathematical models to relate to the different EGFR signaling in NSCLC and normal cells in the presence or absence of EGFR and PTEN mutations. The dynamics of downstream signaling pathways vary in the disease state and activation of some factors can be indicative of drug resistance. Our simulation denotes the effect of EGFR mutations and increased expression of certain factors in NSCLC EGFR signaling on each of the three pathways where levels of pERK, pSTAT and pAkt are increased. Over activation of ERK, Akt and STAT3 which are the main cell proliferation and survival factors act as promoting factors for tumor progression in NSCLC. In case of loss of PTEN, Akt activity level is considerably increased. Our simulation results show that in the presence of erlotinib, downstream factors i.e. pAkt, pSTAT3 and pERK are inhibited. However, in case of loss of PTEN expression in the presence of erlotinib, pAkt level would not decrease which demonstrates that these cells are resistant to erlotinib.. null, 7.\n Laboratory of Systems Biology and Bioinformatics, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran."],"submitter_mail":["bidkhori@ibb.ut.ac.ir"],"submitter_affiliation":["university of tehran"],"publicationId":["BIOMD0000000453"],"pubmed_abstract":["Grb2-associated binder 1 (GAB1) is a scaffold protein involved in numerous interactions that propagate signaling by growth factor and cytokine receptors. Here we explore in silico and validate in vivo the role of GAB1 in the control of mitogenic (Ras/MAPK) and survival (phosphatidylinositol 3-kinase (PI3K)/Akt) signaling stimulated by epidermal growth factor (EGF). We built a comprehensive mechanistic model that allows for reliable predictions of temporal patterns of cellular responses to EGF under diverse perturbations, including different EGF doses, GAB1 suppression, expression of mutant proteins, and pharmacological inhibitors. We show that the temporal dynamics of GAB1 tyrosine phosphorylation is significantly controlled by positive GAB1-PI3K feedback and negative MAPK-GAB1 feedback. Our experimental and computational results demonstrate that the essential function of GAB1 is to enhance PI3K/Akt activation and extend the duration of Ras/MAPK signaling. By amplifying positive interactions between survival and mitogenic pathways, GAB1 plays the critical role in cell proliferation and tumorigenesis.","EGFR signaling plays a very important role in NSCLC. It activates Ras/ERK, PI3K/Akt and STAT activation pathways. These are the main pathways for cell proliferation and survival. We have developed two mathematical models to relate to the different EGFR signaling in NSCLC and normal cells in the presence or absence of EGFR and PTEN mutations. The dynamics of downstream signaling pathways vary in the disease state and activation of some factors can be indicative of drug resistance. Our simulation denotes the effect of EGFR mutations and increased expression of certain factors in NSCLC EGFR signaling on each of the three pathways where levels of pERK, pSTAT and pAkt are increased. Over activation of ERK, Akt and STAT3 which are the main cell proliferation and survival factors act as promoting factors for tumor progression in NSCLC. In case of loss of PTEN, Akt activity level is considerably increased. Our simulation results show that in the presence of erlotinib, downstream factors i.e. pAkt, pSTAT3 and pERK are inhibited. However, in case of loss of PTEN expression in the presence of erlotinib, pAkt level would not decrease which demonstrates that these cells are resistant to erlotinib.","