Prohibitin promotes de-differentiation and is a potential therapeutic target in neuroblastoma
MacArthur I, Bei Y, Garcia H, Ortiz M, Toedling J, Klironomos F, Rolff J, Eggert A, Schulte J, Kentsis A, Henssen A. Prohibitin promotes de-differentiation and is a potential therapeutic target in neuroblastoma. JCI Insight 2019, 5 PMID: 30998507, PMCID: PMC6542629, DOI: 10.1172/jci.insight.127130.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell Cycle CheckpointsCell DedifferentiationCell DifferentiationCell Line, TumorCell ProliferationChild, PreschoolChromosomes, Human, Pair 17HumansMAP Kinase Signaling SystemMiceNeuroblastomaProhibitinsProtein Kinase InhibitorsPyridonesPyrimidinonesRepressor ProteinsRNA-SeqRNA, MessengerSequence Analysis, RNAWhole Genome SequencingXenograft Model Antitumor AssaysConceptsLong arm of chromosome 17Neuroblastoma cellsSlow cell cycle progressionExpression of prohibitinImpaired ERK1/2 activationGene expression programsWhole genomeHigh-risk neuroblastomaChromosome 17Long armDe-differentiationPromote tumor cell proliferationTumor cell proliferationRNA sequencingAssociated with suppressionEctopic expressionProhibitinProliferation of neuroblastoma cellsCytogenetic hallmarkProhibitin expressionExpression programsAssociated with lossNeuronal developmentERK1/2 activationNeuroblastoma outcomeSynergistic activity of BET inhibitor MK-8628 and PLK inhibitor Volasertib in preclinical models of medulloblastoma
Han Y, Lindner S, Bei Y, Garcia H, Timme N, Althoff K, Odersky A, Schramm A, Lissat A, Künkele A, Deubzer H, Eggert A, Schulte J, Henssen A. Synergistic activity of BET inhibitor MK-8628 and PLK inhibitor Volasertib in preclinical models of medulloblastoma. Cancer Letters 2019, 445: 24-33. PMID: 30611741, DOI: 10.1016/j.canlet.2018.12.012.Peer-Reviewed Original ResearchConceptsModel of medulloblastomaMYC-amplified medulloblastomaMK-8628Preclinical models of medulloblastomaAnti-tumor effectsPreclinical modelsTherapeutic efficacyCentral nervous system tumorsAggressive clinical courseHigh-risk medulloblastomaTherapy-related morbidityCurrent treatment regimensNervous system tumorsTargeted treatment approachesBET protein BRD4MYC protein stabilityIn vivo modelsMYC amplificationMedulloblastoma modelApoptotic cell deathCell cycle arrestClinical courseTreatment regimensSystem tumorsTarget of Plk1
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