2024
Cell-specific models reveal conformation-specific RAF inhibitor combinations that synergistically inhibit ERK signaling in pancreatic cancer cells
Sevrin T, Imoto H, Robertson S, Rauch N, Dyn'ko U, Koubova K, Wynne K, Kolch W, Rukhlenko O, Kholodenko B. Cell-specific models reveal conformation-specific RAF inhibitor combinations that synergistically inhibit ERK signaling in pancreatic cancer cells. Cell Reports 2024, 43: 114710. PMID: 39240715, PMCID: PMC11474227, DOI: 10.1016/j.celrep.2024.114710.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaResistance to RAFResistant PDAC cellsPancreatic cancer cellsPancreatic ductal adenocarcinoma cell linesProtein expression profilesTumor-specific variationsIsogenic pairsCell-specific modelsConformational specificityERK signalingInhibitor combinationsERK pathwayKRAS mutationsTargeted therapyExpression profilesMEK inhibitorsDuctal adenocarcinomaCancer cellsKRAS mutantPhospho-ERKCell linesPDAC cellsCell viabilityDifferential sensitivity
2009
Systems‐level interactions between insulin–EGF networks amplify mitogenic signaling
Borisov N, Aksamitiene E, Kiyatkin A, Legewie S, Berkhout J, Maiwald T, Kaimachnikov NP, Timmer J, Hoek JB, Kholodenko BN. Systems‐level interactions between insulin–EGF networks amplify mitogenic signaling. Molecular Systems Biology 2009, 5: msb200919. PMID: 19357636, PMCID: PMC2683723, DOI: 10.1038/msb.2009.19.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingCell LineDose-Response Relationship, DrugDrug SynergismEnzyme ActivationEpidermal Growth FactorGRB2 Adaptor ProteinHumansImmunoprecipitationInsulinMitogen-Activated Protein KinasesMitogensModels, BiologicalPhosphoinositide-3 Kinase InhibitorsPhosphorylationProtein Kinase InhibitorsProtein Tyrosine Phosphatase, Non-Receptor Type 11Ras ProteinsReproducibility of ResultsSignal TransductionSrc-Family KinasesSystems BiologyConceptsInsulin receptor substrateEpidermal growth factorRas/ERK cascadeCrosstalk mechanismsComplex cellular responsesPhosphatase SHP2Mitogenic signalingERK cascadeSrc kinaseReceptor substrateERK activityRaf levelsInsulin-induced increaseERK activationCellular responsesGab1HEK293 cellsExternal cuesEGF dosesPoor activatorGrowth factorMitogenicMitogenic responseComputational approachSHP2