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
2020
Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRASG13D
Kennedy S, Jarboui M, Srihari S, Raso C, Bryan K, Dernayka L, Charitou T, Bernal-Llinares M, Herrera-Montavez C, Krstic A, Matallanas D, Kotlyar M, Jurisica I, Curak J, Wong V, Stagljar I, LeBihan T, Imrie L, Pillai P, Lynn M, Fasterius E, Al-Khalili Szigyarto C, Breen J, Kiel C, Serrano L, Rauch N, Rukhlenko O, Kholodenko B, Iglesias-Martinez L, Ryan C, Pilkington R, Cammareri P, Sansom O, Shave S, Auer M, Horn N, Klose F, Ueffing M, Boldt K, Lynn D, Kolch W. Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRASG13D. Nature Communications 2020, 11: 499. PMID: 31980649, PMCID: PMC6981206, DOI: 10.1038/s41467-019-14224-9.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptor (EGFR) networkGrowth factor receptor networkFundamental biological processesColorectal cancer cellsCancer cellsEGFR networkTranscriptional regulationProtein complexesExtensive rewiringCellular phenotypesInteraction networksBiological processesOncogenic mutationsOncogenic KRAS mutationsReceptor networkGenetic alterationsProtein expressionPPInsMutationsCellsInteractorsPhosphorylationRewiringPoor patient outcomesSignal flow
2018
PO-136 Studying pathway interactions and dynamics to predict cell responses to chemotherapeutic treatment in breast cancer cells
Tuffery L, Kholodenko B, Kolch W, Halasz M, Fey D. PO-136 Studying pathway interactions and dynamics to predict cell responses to chemotherapeutic treatment in breast cancer cells. ESMO Open 2018, 3: a279. DOI: 10.1136/esmoopen-2018-eacr25.660.Peer-Reviewed Original ResearchBreast cancer cell linesDoxorubicin treatmentCancer cell linesCell linesDifferent breast cancer cell linesBreast cancer cellsMCF10A cellsDifferent mutation patternsMechanism of actionPhosphorylation of JNKBreast cancer tumor samplesCommon cancerPatient responseTreatment strategiesBreast cancerTreatment responseChemotherapeutic treatmentCell responsesFlow cytometryTumor samplesWestern blotNon-cancerous cellsChemotherapeutic drugsPathway interactionsCancer cells
2015
Signalling mechanisms regulating phenotypic changes in breast cancer cells
Volinsky N, McCarthy CJ, von Kriegsheim A, Saban N, Okada-Hatakeyama M, Kolch W, Kholodenko BN. Signalling mechanisms regulating phenotypic changes in breast cancer cells. Bioscience Reports 2015, 35: e00178. PMID: 25643809, PMCID: PMC4370098, DOI: 10.1042/bsr20140172.Peer-Reviewed Original ResearchConceptsCell fate decisionsATP-citrate lyaseFate decisionsPhenotypic changesBreast cancer cellsEpidermal growth factorCell fate decision processesCancer cellsLipid accumulationIrreversible phenotypic changesPhosphoinositide-3 kinaseSimilar cellular responsesPI3K pathwayGrowth factorRapamycin complexKinase pathwayNegative regulatorMolecular mechanismsCellular responsesMetabolic pathwaysMammalian targetK pathwayCitrate lyaseLipogenic pathwayCell proliferation