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Prohibitin promotes dedifferentiation and is a potential therapeutic target in neuroblastoma

Item Type:Article
Title:Prohibitin promotes dedifferentiation and is a potential therapeutic target in neuroblastoma
Creators Name:MacArthur, I.C. and Bei, Y. and Garcia, H.D. and Ortiz, M.V. and Toedling, J. and Klironomos, F. and Rolff, J. and Eggert, A. and Schulte, J.H. and Kentsis, A. and Henssen, A.G.
Abstract:Gain of the long arm of chromosome 17 (17q) is a cytogenetic hallmark of high-risk neuroblastoma, yet its contribution to neuroblastoma pathogenesis remains incompletely understood. Combining whole-genome and RNA sequencing of neuroblastomas, we identified the prohibitin (PHB) gene as highly expressed in tumors with 17q gain. High PHB expression correlated with poor prognosis and was associated with loss of gene expression programs promoting neuronal development and differentiation. PHB depletion induced differentiation and apoptosis and slowed cell cycle progression of neuroblastoma cells, at least in part through impaired ERK1/2 activation. Conversely, ectopic expression of PHB was sufficient to increase proliferation of neuroblastoma cells and was associated with suppression of markers associated with neuronal differentiation and favorable neuroblastoma outcome. Thus, PHB is a 17q oncogene in neuroblastoma that promotes tumor cell proliferation and dedifferentiation.
Keywords:Apoptosis, Cell Cycle Checkpoints, Cell Dedifferentiation, Cell Differentiation, Cell Proliferation, MAP Kinase Signaling System, Messenger RNA, Neuroblastoma, Pair 17 Human Chromosomes, Protein Kinase Inhibitors, Pyridones, Pyrimidinones, RNA Sequence Analysis, RNA-Seq, Repressor Proteins, Tumor Cell Line, Whole Genome Sequencing, Xenograft Model Antitumor Assays, Animals, Mice
Source:JCI Insight
Publisher:American Society for Clinical Investigation
Page Range:e127130
Date:16 May 2019
Official Publication:https://doi.org/10.1172/jci.insight.127130
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

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