Prohibitin promotes de-differentiation and is a potential therapeutic target in neuroblastoma

JCI Insight. 2019 Apr 18;5(10):e127130. doi: 10.1172/jci.insight.127130.


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 de-differentiation.

Keywords: Cancer; Genetics; Oncogenes; Oncology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Cycle Checkpoints / genetics
  • Cell Dedifferentiation / genetics*
  • Cell Differentiation / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Child, Preschool
  • Chromosomes, Human, Pair 17 / genetics
  • Humans
  • MAP Kinase Signaling System
  • Mice
  • Neuroblastoma / genetics*
  • Prohibitins
  • Protein Kinase Inhibitors / pharmacology
  • Pyridones / pharmacology
  • Pyrimidinones / pharmacology
  • RNA, Messenger / metabolism
  • RNA-Seq
  • Repressor Proteins / genetics*
  • Sequence Analysis, RNA
  • Whole Genome Sequencing
  • Xenograft Model Antitumor Assays


  • PHB protein, human
  • Prohibitins
  • Protein Kinase Inhibitors
  • Pyridones
  • Pyrimidinones
  • RNA, Messenger
  • Repressor Proteins
  • trametinib