6533b7d0fe1ef96bd125b975
RESEARCH PRODUCT
Integrative genomic and proteomic analyses identify targets for Lkb1 deficient metastatic lung tumors
Nabeel BardeesyNeil HayesKwok-kin WongKwok-kin WongKathleyn A. BrandstetterAutumn L. JacksonSauveur Michel MairaDiego H. CastrillonJulian CarreteroKate McnamaraNorman E. SharplessKatherine CrosbyMatthew S. ButtarazziHongbin JiChrista L. BorgmanKlarisa RikovaBenjamin A. SanofskyJeffrey A. EngelmanGeoffrey I. ShapiroGeoffrey I. ShapiroWilliam Y. KimCarla F. KimCarlos Garcia-echeverriaTing-lei GuTakeshi ShimamuraTakeshi ShimamuraZandra E. WaltonJeffrey C. SilvaMatthew D. Wilkersonsubject
ProteomicsCancer ResearchLung NeoplasmsMAP Kinase Kinase 2MAP Kinase Kinase 1CELLCYCLEAMP-Activated Protein Kinasesmedicine.disease_causeMice0302 clinical medicineAMP-Activated Protein Kinase KinasesCell MovementCarcinoma Non-Small-Cell LungEnzyme InhibitorsNeoplasm MetastasisPhosphorylationLymph nodePhosphoinositide-3 Kinase Inhibitors0303 health sciencesTOR Serine-Threonine KinasesIntracellular Signaling Peptides and ProteinsGenomicsCell cycleProtein-Tyrosine KinasesPenetrance3. Good healthUp-RegulationGene Expression Regulation Neoplasticmedicine.anatomical_structuresrc-Family KinasesOncologySIGNALING030220 oncology & carcinogenesisDrug Therapy CombinationFemaleRNA InterferenceKRASSignal TransductionMice NudeBiologyProtein Serine-Threonine KinasesArticleProto-Oncogene Proteins p21(ras)03 medical and health sciencesCell Line TumorProto-Oncogene ProteinsmedicineCell AdhesionAnimalsHumansEpithelial–mesenchymal transitionProtein Kinase Inhibitors030304 developmental biologyFocal AdhesionsGene Expression ProfilingCell BiologyXenograft Model Antitumor AssaysMice Mutant StrainsGene expression profilingFocal Adhesion Protein-Tyrosine KinasesCancer cellCell TransdifferentiationCancer researchras ProteinsCarcinogenesisdescription
SummaryIn mice, Lkb1 deletion and activation of KrasG12D results in lung tumors with a high penetrance of lymph node and distant metastases. We analyzed these primary and metastatic de novo lung cancers with integrated genomic and proteomic profiles, and have identified gene and phosphoprotein signatures associated with Lkb1 loss and progression to invasive and metastatic lung tumors. These studies revealed that SRC is activated in Lkb1-deficient primary and metastatic lung tumors, and that the combined inhibition of SRC, PI3K, and MEK1/2 resulted in synergistic tumor regression. These studies demonstrate that integrated genomic and proteomic analyses can be used to identify signaling pathways that may be targeted for treatment.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2010-06-01 |