2016
Combination inhibition of PI3K and mTORC1 yields durable remissions in mice bearing orthotopic patient-derived xenografts of HER2-positive breast cancer brain metastases
Ni J, Ramkissoon SH, Xie S, Goel S, Stover DG, Guo H, Luu V, Marco E, Ramkissoon LA, Kang YJ, Hayashi M, Nguyen QD, Ligon AH, Du R, Claus EB, Alexander BM, Yuan GC, Wang ZC, Iglehart JD, Krop IE, Roberts TM, Winer EP, Lin NU, Ligon KL, Zhao JJ. Combination inhibition of PI3K and mTORC1 yields durable remissions in mice bearing orthotopic patient-derived xenografts of HER2-positive breast cancer brain metastases. Nature Medicine 2016, 22: 723-726. PMID: 27270588, PMCID: PMC4938731, DOI: 10.1038/nm.4120.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAminopyridinesAnimalsAntineoplastic AgentsApoptosisBrain NeoplasmsBreast NeoplasmsCarrier ProteinsCaspase 3Cell Cycle ProteinsDNA RepairDrug Resistance, NeoplasmDrug Therapy, CombinationEukaryotic Initiation FactorsEverolimusFemaleGene Expression ProfilingGenomic InstabilityHumansImmunohistochemistryKi-67 AntigenMagnetic Resonance ImagingMechanistic Target of Rapamycin Complex 1MiceMice, SCIDMolecular Targeted TherapyMorpholinesMultiprotein ComplexesNeoplasm TransplantationPhosphoinositide-3 Kinase InhibitorsPhosphoproteinsPhosphorylationReceptor, ErbB-2Remission InductionTOR Serine-Threonine KinasesXenograft Model Antitumor AssaysConceptsBreast cancer brain metastasesCancer brain metastasesBrain metastasesHER2-positive breast cancer brain metastasesOrthotopic patient-derived xenograftsPI3KPatient-derived xenograftsDurable remissionsTherapeutic responseMouse modelCombined inhibitionCombination inhibitionMetastasisInhibitionRemissionXenograftsMice
2014
Phosphorylation of ETS1 by Src Family Kinases Prevents Its Recognition by the COP1 Tumor Suppressor
Lu G, Zhang Q, Huang Y, Song J, Tomaino R, Ehrenberger T, Lim E, Liu W, Bronson RT, Bowden M, Brock J, Krop IE, Dillon DA, Gygi SP, Mills GB, Richardson AL, Signoretti S, Yaffe MB, Kaelin WG. Phosphorylation of ETS1 by Src Family Kinases Prevents Its Recognition by the COP1 Tumor Suppressor. Cancer Cell 2014, 26: 222-234. PMID: 25117710, PMCID: PMC4169234, DOI: 10.1016/j.ccr.2014.06.026.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBinding SitesFemaleHCT116 CellsHEK293 CellsHumansMiceMice, Inbred NODMice, SCIDMolecular Sequence DataNeoplasm TransplantationPhosphorylationProtein BindingProto-Oncogene Protein c-ets-1Proto-Oncogene Protein c-ets-2Src-Family KinasesTriple Negative Breast NeoplasmsTumor BurdenUbiquitinationUbiquitin-Protein LigasesConceptsSrc family kinasesFamily kinasesTumor suppressorPhosphorylation of ETS1Ubiquitin ligase componentTumor suppressor proteinAnchorage-independent growthNeighboring tyrosine residueCOP1 substratesRegulatory phosphorylationSpecific serineThreonine residuesSrc familySuppressor proteinTyrosine residuesETS1Breast cancer cellsPhosphorylationCancer cellsNeoplastic growthKinaseSuppressorProteinOncoproteinResidues