Prohibitin promotes dedifferentiation and is a potential therapeutic target in neuroblastoma Journal Article
| Authors: | MacArthur, I. C.; Bei, Y.; Garcia, H. D.; Ortiz, M. V.; Toedling, J.; Klironomos, F.; Rolff, J.; Eggert, A.; Schulte, J. H.; Kentsis, A.; Henssen, A. G. |
| Article Title: | Prohibitin promotes dedifferentiation and is a potential therapeutic target in neuroblastoma |
| 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 identifed 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 di?erentiation. PHB depletion induced di?erentiation 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 sufcient to increase proliferation of neuroblastoma cells and was associated with suppression of markers associated with neuronal di?erentiation and favorable neuroblastoma outcome. Thus, PHB is a 17q oncogene in neuroblastoma that promotes tumor cell proliferation and dedi?erentiation. © 2019 American Society for Clinical Investigation. |
| Keywords: | controlled study; unclassified drug; gene mutation; human cell; drug potentiation; nonhuman; drug targeting; antineoplastic agent; cell proliferation; mouse; cell cycle progression; apoptosis; gene expression; animal experiment; animal model; antineoplastic activity; enzyme activation; carcinogenesis; oncogene; neuroblastoma; neuroblastoma cell; mitogen activated protein kinase 1; mitogen activated protein kinase 3; gene loss; nerve cell differentiation; chromosome 17q; cell dedifferentiation; ectopic expression; cancer prognosis; trametinib; mapk signaling; human; article; prohibitin; rocaglamide a; concentration (parameter); phb gene |
| Journal Title: | JCI Insight |
| Volume: | 4 |
| Issue: | 10 |
| ISSN: | 2379-3708 |
| Publisher: | Amer Soc Clinical Investigation Inc |
| Date Published: | 2019-05-01 |
| Start Page: | e127130 |
| Language: | English |
| DOI: | 10.1172/jci.insight.127130 |
| PUBMED: | 30998507 |
| PROVIDER: | scopus |
| PMCID: | PMC6542629 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 4 September 2019 -- Source: Scopus |
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