An Interaction with Ewing's Sarcoma Breakpoint Protein EWS Defines a Specific Oncogenic Mechanism of ETS Factors Rearranged in Prostate Cancer

Cell Rep. 2016 Oct 25;17(5):1289-1301. doi: 10.1016/j.celrep.2016.10.001.

Abstract

More than 50% of prostate tumors have a chromosomal rearrangement resulting in aberrant expression of an oncogenic ETS family transcription factor. However, mechanisms that differentiate the function of oncogenic ETS factors expressed in prostate tumors from non-oncogenic ETS factors expressed in normal prostate are unknown. Here, we find that four oncogenic ETS (ERG, ETV1, ETV4, and ETV5), and no other ETS, interact with the Ewing's sarcoma breakpoint protein, EWS. This EWS interaction was necessary and sufficient for oncogenic ETS functions including gene activation, cell migration, clonogenic survival, and transformation. Significantly, the EWS interacting region of ERG has no homology with that of ETV1, ETV4, and ETV5. Therefore, this finding may explain how divergent ETS factors have a common oncogenic function. Strikingly, EWS is fused to various ETS factors by the chromosome translocations that cause Ewing's sarcoma. Therefore, these findings link oncogenic ETS function in both prostate cancer and Ewing's sarcoma.

Keywords: ERG; ETS; EWS; Ewing’s sarcoma; prostate cancer.

Publication types

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

MeSH terms

  • Animals
  • Carcinogenesis / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Gene Rearrangement / genetics*
  • Humans
  • Male
  • Mice, Nude
  • Oncogenes*
  • Phenotype
  • Promoter Regions, Genetic / genetics
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology*
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Proto-Oncogene Protein c-ets-1 / metabolism*
  • RNA-Binding Protein EWS / metabolism*
  • Sarcoma, Ewing / pathology*
  • Transcription Factors / metabolism

Substances

  • Proto-Oncogene Protein c-ets-1
  • RNA-Binding Protein EWS
  • Transcription Factors