Myogenic regulatory transcription factors regulate growth in rhabdomyosarcoma

Elife. 2017 Jan 12:6:e19214. doi: 10.7554/eLife.19214.

Abstract

Rhabdomyosarcoma (RMS) is a pediatric malignacy of muscle with myogenic regulatory transcription factors MYOD and MYF5 being expressed in this disease. Consensus in the field has been that expression of these factors likely reflects the target cell of transformation rather than being required for continued tumor growth. Here, we used a transgenic zebrafish model to show that Myf5 is sufficient to confer tumor-propagating potential to RMS cells and caused tumors to initiate earlier and have higher penetrance. Analysis of human RMS revealed that MYF5 and MYOD are mutually-exclusively expressed and each is required for sustained tumor growth. ChIP-seq and mechanistic studies in human RMS uncovered that MYF5 and MYOD bind common DNA regulatory elements to alter transcription of genes that regulate muscle development and cell cycle progression. Our data support unappreciated and dominant oncogenic roles for MYF5 and MYOD convergence on common transcriptional targets to regulate human RMS growth.

Keywords: cancer biology; developmental biology; human; muscle; myf5; myoD; rhabdomyosarcoma; stem cells; zebrafish.

Publication types

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

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Chromatin Immunoprecipitation
  • Humans
  • MyoD Protein / metabolism*
  • Myogenic Regulatory Factor 5 / metabolism*
  • Rhabdomyosarcoma / physiopathology*
  • Sequence Analysis, DNA
  • Transcription, Genetic*
  • Zebrafish

Substances

  • MYF5 protein, human
  • MyoD Protein
  • Myogenic Regulatory Factor 5