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

Vivekananda Kedage, Nagarathinam Selvaraj, Taylor R. Nicholas, Justin A. Budka, Joshua P. Plotnik, Travis J. Jerde, Peter C. Hollenhorst

Research output: Contribution to journalArticle

11 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1289-1301
Number of pages13
JournalCell Reports
Volume17
Issue number5
DOIs
StatePublished - Oct 25 2016

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Keywords

  • ERG
  • ETS
  • EWS
  • Ewing's sarcoma
  • prostate cancer

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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