grant
Role of the CTLH E3 ubiquitin ligase in breast cancer progression
Organization UNIVERSITY OF IOWALocation IOWA CITY, UNITED STATESPosted 1 Apr 2024Deadline 31 Mar 2029
NIHUS FederalResearch GrantFY2026APF-1ASVSRC1ATP-Dependent Proteolysis Factor 1Anti-ERB-2Anti-HER2/c-erbB2 Monoclonal AntibodyAnti-c-ERB-2Anti-c-erbB2 Monoclonal AntibodyAnti-erbB-2Anti-erbB2 Monoclonal AntibodyAnti-p185-HER2Automobile DrivingBAF47BAF47 GeneBreast CancerBreast CarcinomaBreast NeoplasmsBreast TumorsCancer TreatmentCell Communication and SignalingCell LineCell SignalingCellLineComplexD-GlucoseDataDevelopmentDextroseDrug resistanceDrugsE3 LigaseE3 Ubiquitin LigaseERBB2ERBB2 geneEffectivenessEnhancersEpigeneticEpigenetic ChangeEpigenetic MechanismEpigenetic ProcessG Protein GoG Protein-Complex ReceptorG Protein-Coupled Receptor GenesG Protein-Coupled Receptor SignalingG(o) ProteinG-Protein-Coupled ReceptorsG-ProteinsGPCRGPCR SignalingGTP-Binding ProteinsGTP-Regulatory ProteinsGene DeletionGene TranscriptionGeneralized GrowthGeneticGenetic TranscriptionGlucoseGo Alpha SubunitGo Subunit G-ProteinGrowthGuanine Nucleotide Coupling ProteinGuanine Nucleotide Regulatory ProteinsGuanine Nucleotide-Binding Protein GoHER -2HER-2HER2HER2 GenesHER2 Monoclonal AntibodyHER2/neuHMG-20HerceptinHigh Mobility Protein 20INI1INI1 GeneInhibitory Go G-ProteinIntracellular Communication and SignalingKnowledgeMalignant Breast NeoplasmMalignant Neoplasm TherapyMalignant Neoplasm TreatmentMammary CancerMammary CarcinomaMammary NeoplasmsMediatingMedicationMetastasisMetastasis to the LungMetastasizeMetastatic LesionMetastatic MassMetastatic NeoplasmMetastatic Neoplasm to the LungMetastatic TumorMetastatic Tumor to the LungMoAb HER2ModelingNEU OncogeneNEU proteinNeoplasm MetastasisNuclearNuclear TranslocationOncogene ErbB2OncogenesisOncogenicOrthologOrthologous GenePDX modelPI-3K/AKTPI3K/AKTPathway interactionsPatient derived xenograftPharmaceutical PreparationsPrognosisProteinsRNA ExpressionRecurrent NeoplasmRecurrent tumorResistanceRoleSMARCB1SMARCB1 geneSNF5SNF5 GeneSNF5L1SNF5L1 GeneSRC Family GeneSRC geneSWI/SNF Related, Matrix Associated, Actin Dependent Regulator of Chromatin, Subfamily B, Member 1 GeneScaffolding ProteinSecondary NeoplasmSecondary TumorSignal TransductionSignal Transduction SystemsSignalingSignaling Factor Proto-OncogeneSignaling Pathway GeneSignaling ProteinStrains Cell LinesSubgroupTKR1TestingTissue GrowthTranscriptionTransgenic MiceTrastuzumabTumor CellTumor PromotionTumor Suppressor ProteinsUbiquitilationUbiquitinUbiquitin Ligase Component GeneUbiquitin Ligase GeneUbiquitin Protein LigaseUbiquitin-Protein Ligase ComplexesUbiquitin-Protein Ligase E3UbiquitinationUbiquitinoylationUpregulationYeastsanti-cancer therapybiological signal transductionbreast cancer progressionc srcc-erb-2 Monoclonal Antibodyc-erbB-2c-erbB-2 Genesc-erbB-2 Proto-Oncogenesc-src Genesc-src Proto-Oncogenescancer initiationcancer metastasiscancer progressioncancer therapycancer-directed therapyclinical relevanceclinically relevantcultured cell linedevelopmentaldrivingdrug resistantdrug/agentepigeneticallyerbB-2 Genesexpression subtypesgene deletion mutationhSNF5/INI1 Geneherstatinimprovedlapatiniblung metastasismalignant breast tumormammarymammary tumormetastasize to the lungmolecular sub-typesmolecular subsetsmolecular subtypesmouse modelmurine modelneoplasm progressionneoplasm recurrenceneoplastic cellneoplastic progressionneu Genesnew drug targetnew drug treatmentsnew druggable targetnew drugsnew pharmacological therapeuticnew pharmacotherapy targetnew therapeutic targetnew therapeuticsnew therapynew therapy targetnext generation therapeuticsnovelnovel drug targetnovel drug treatmentsnovel druggable targetnovel drugsnovel pharmaco-therapeuticnovel pharmacological therapeuticnovel pharmacotherapy targetnovel therapeutic targetnovel therapeuticsnovel therapynovel therapy targetontogenyoverexpressoverexpressionpathwaypatient derived xenograft modelpreventpreventingprogramspulmonary metastasisrecruitresistance to Drugresistance to therapyresistantresistant to Drugresistant to therapyresponserhuMAb HER2scaffoldscaffoldingsocial roletargeted drug therapytargeted drug treatmentstargeted therapeutictargeted therapeutic agentstargeted therapytargeted treatmenttherapeutic resistancetherapy resistanttreatment resistancetumortumor cell metastasistumor growthtumor initiationtumor progressiontumor suppressortumorigenesistumorigenicubiquinationubiquitin conjugationubiquitin ligaseubiquitin-protein ligasev-SRC Avian Sarcoma (Schmidt-Ruppin A-2) Viral Oncogene Homolog
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Project Summary / Abstract
HER2-positive breast cancers are highly aggressive and associated with poor prognosis. HER2-targeted
therapy is the preferred treatment for these cancers, but drug resistance is a major problem. Our previous studies
demonstrated that dysregulation of G protein coupled receptors, in particular, a subgroup of GPCRs that…
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