2017
Phosphorylated cortactin recruits Vav2 guanine nucleotide exchange factor to activate Rac3 and promote invadopodial function in invasive breast cancer cells
Rosenberg BJ, Gil-Henn H, Mader CC, Halo T, Yin T, Condeelis J, Machida K, Wu YI, Koleske AJ. Phosphorylated cortactin recruits Vav2 guanine nucleotide exchange factor to activate Rac3 and promote invadopodial function in invasive breast cancer cells. Molecular Biology Of The Cell 2017, 28: 1347-1360. PMID: 28356423, PMCID: PMC5426849, DOI: 10.1091/mbc.e16-12-0885.Peer-Reviewed Original ResearchConceptsInvasive breast cancer cellsInvadopodium maturationBreast cancer cellsActin nucleation-promoting factorCancer cellsSH2 domain bindsHuman SH2 domainsMatrix degradationNucleation-promoting factorsGuanine nucleotide exchange factor Vav2Actin-rich protrusionsSubsequent cell invasionExchange factor Vav2Active Rac3Invasive MDA-MB-231 breast cancer cellsMDA-MB-231 breast cancer cellsInvadopodial functionSH2 domainDomain bindsExchange factorKinase cascadeCortactin phosphorylationActin polymerizationMutant formsInvadopodia
2012
Arg/Abl2 promotes invasion and attenuates proliferation of breast cancer in vivo
Gil-Henn H, Patsialou A, Wang Y, Warren MS, Condeelis JS, Koleske AJ. Arg/Abl2 promotes invasion and attenuates proliferation of breast cancer in vivo. Oncogene 2012, 32: 2622-2630. PMID: 22777352, PMCID: PMC3473103, DOI: 10.1038/onc.2012.284.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBreast NeoplasmsCell Line, TumorCell ProliferationErbB ReceptorsFemaleGene Knockdown TechniquesHumansLung NeoplasmsMAP Kinase Signaling SystemMiceMice, SCIDNeoplasm InvasivenessNeoplasm MetastasisNeoplasm TransplantationProto-Oncogene Proteins c-ablSrc-Family KinasesTransplantation, HeterologousConceptsTumor cell invasionBreast cancer cellsTyrosine kinaseCancer cellsCell invasionNon-receptor tyrosine kinaseRas-MAPK signalingRas-MAPK pathwayGene expression patternsSrc tyrosine kinaseInvasion-associated genesUncontrolled cell divisionProliferation-associated genesMetastatic cancer cellsCell divisionExpression patternsEGF receptorTumor cell proliferationPromotes InvasionMouse xenograft modelCell proliferationMultistep processGenetic aberrationsKinaseGenes
2011
Cortactin phosphorylation regulates cell invasion through a pH-dependent pathway
Magalhaes MA, Larson DR, Mader CC, Bravo-Cordero JJ, Gil-Henn H, Oser M, Chen X, Koleske AJ, Condeelis J. Cortactin phosphorylation regulates cell invasion through a pH-dependent pathway. Journal Of Cell Biology 2011, 195: 903-920. PMID: 22105349, PMCID: PMC3257566, DOI: 10.1083/jcb.201103045.Peer-Reviewed Original ResearchMeSH KeywordsActin Depolymerizing FactorsAdaptor Proteins, Signal TransducingCation Transport ProteinsCell Line, TumorCell Surface ExtensionsCortactinHumansHydrogen-Ion ConcentrationModels, BiologicalNeoplasm InvasivenessOncogene ProteinsPhosphorylationSodium-Hydrogen Exchanger 1Sodium-Hydrogen ExchangersConceptsCortactin phosphorylationCell invasionInvadopodia maturationCortactin tyrosine phosphorylationPH-dependent regulationInvasive protrusionsPH-dependent pathwayCofilin activityCofilin regulationTyrosine phosphorylationExchanger NHE1Cofilin activationPhosphorylationInvadopodiaProteolytic activityPrecise mechanismInvasionNHE1RegulationDynamic cyclePathwayMaturationTumor cellsNck1CofilinAn EGFR–Src–Arg–Cortactin Pathway Mediates Functional Maturation of Invadopodia and Breast Cancer Cell Invasion
Mader CC, Oser M, Magalhaes MA, Bravo-Cordero JJ, Condeelis J, Koleske AJ, Gil-Henn H. An EGFR–Src–Arg–Cortactin Pathway Mediates Functional Maturation of Invadopodia and Breast Cancer Cell Invasion. Cancer Research 2011, 71: 1730-1741. PMID: 21257711, PMCID: PMC3057139, DOI: 10.1158/0008-5472.can-10-1432.Peer-Reviewed Original ResearchConceptsBreast cancer cell invasionActin polymerizationCancer cell invasionInvadopodium maturationCell invasionCortactin phosphorylationEGFR-SrcExtracellular matrixTumor cell invasionInvadopodia functionV-SrcProtein cortactinEpidermal growth factorKnockdown cellsInvadopodiaFunctional maturationMaster switchSrc overexpressionCandidate therapeutic targetInvasive carcinoma cellsECM degradationNovel mechanismPhosphorylationNovel mediatorArg activationThe vacuolar-ATPase modulates matrix metalloproteinase isoforms in human pancreatic cancer
Chung C, Mader CC, Schmitz J, Atladottir J, Fitchev P, Cornwell M, Koleske AJ, Crawford SE, Gorelick F. The vacuolar-ATPase modulates matrix metalloproteinase isoforms in human pancreatic cancer. Laboratory Investigation 2011, 91: 732-743. PMID: 21339745, PMCID: PMC3084324, DOI: 10.1038/labinvest.2011.8.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaMMP-9 activityHuman pancreatic cancerPancreatic cancerPanIN lesionsHigh-grade PanIN lesionsHuman pancreatic ductal adenocarcinomaPancreatic intraepithelial neoplasmsCancer cellsLow-grade PanIN lesionsMatrix metalloproteinase activationMMP-2 activityPancreatic cancer cellsHuman cancer tissuesShort hairpin RNAPancreatic histologyIntraepithelial neoplasmDuctal adenocarcinomaNormal ductsMMP releaseCancer tissuesMMP-2Metalloproteinase activationInvasive propertiesSpecific MMPs
2010
Specific tyrosine phosphorylation sites on cortactin regulate Nck1-dependent actin polymerization in invadopodia
Oser M, Mader CC, Gil-Henn H, Magalhaes M, Bravo-Cordero JJ, Koleske AJ, Condeelis J. Specific tyrosine phosphorylation sites on cortactin regulate Nck1-dependent actin polymerization in invadopodia. Journal Of Cell Science 2010, 123: 3662-3673. PMID: 20971703, PMCID: PMC3037016, DOI: 10.1242/jcs.068163.Peer-Reviewed Original ResearchConceptsTyrosine phosphorylation sitesTumor cell invasionActin polymerizationPhosphorylation sitesCell invasionTyrosine 421Actin barbed endsPhosphorylation of tyrosineRegulatory switchSH2 domainMembrane protrusionsInvadopodiaCrucial residuesCortactinBarbed endsDirect bindingInvasive carcinoma cellsPhosphorylationNck1Carcinoma cellsFRET interactionsInvasionCellsPhosphotyrosineSites
2009
Cortactin regulates cofilin and N-WASp activities to control the stages of invadopodium assembly and maturation
Oser M, Yamaguchi H, Mader CC, Bravo-Cordero JJ, Arias M, Chen X, DesMarais V, van Rheenen J, Koleske AJ, Condeelis J. Cortactin regulates cofilin and N-WASp activities to control the stages of invadopodium assembly and maturation. Journal Of Cell Biology 2009, 186: 571-587. PMID: 19704022, PMCID: PMC2733743, DOI: 10.1083/jcb.200812176.Peer-Reviewed Original ResearchMeSH KeywordsActin Depolymerizing FactorsActin-Related Protein 2-3 ComplexActinsAdaptor Proteins, Signal TransducingAnimalsCell Line, TumorCortactinEpidermal Growth FactorExtracellular MatrixHumansMammary Neoplasms, AnimalMatrix Metalloproteinase 14Neoplasm InvasivenessOncogene Protein pp60(v-src)Oncogene ProteinsPhosphorylationProtein Structure, TertiaryRatsRecombinant Fusion ProteinsRNA, Small InterferingTyrosineWiskott-Aldrich Syndrome Protein, NeuronalConceptsInvadopodium assemblyActin polymerizationCortactin phosphorylationArp2/3 complex-dependent actin polymerizationArp2/3-dependent actin polymerizationComplex-dependent actin polymerizationBarbed end formationN-WASP activityCarcinoma cellsMembrane protrusionsEnd formationSevering activityInvadopodiaMaster switchActin filamentsBarbed endsCortactinInvasive carcinoma cellsMetastatic carcinoma cellsNovel mechanismPhosphorylationCofilinMatrix degradationMaturationAssembly