Common ELF1 deletion in prostate cancer bolsters oncogenic ets function, inhibits senescence and promotes docetaxel resistance

Justin A. Budka, Mary W. Ferris, Matthew J. Capone, Peter Hollenhorst

Research output: Contribution to journalArticle

Abstract

ETS family transcription factors play major roles in prostate tumorigenesis with some acting as oncogenes and others as tumor suppressors. ETS factors can compete for binding at some cis-regulatory sequences, but display specific binding at others. Therefore, changes in expression of ETS family members during tumorigenesis can have complex, multimodal effects. Here we show that ELF1 was the most commonly down-regulated ETS factor in primary prostate tumors, and expression decreased further in metastatic disease. Genome-wide mapping in cell lines indicated that ELF1 has two distinct tumor suppressive roles mediated by distinct cis-regulatory sequences. First, ELF1 inhibited cell migration and epithelial-mesenchymal transition by interfering with oncogenic ETS functions at ETS/AP-1 cis-regulatory motifs. Second, ELF1 uniquely targeted and activated genes that promote senescence. Furthermore, knockdown of ELF1 increased docetaxel resistance, indicating that the genomic deletions found in metastatic prostate tumors may promote therapeutic resistance through loss of both RB1 and ELF1.

Original languageEnglish (US)
Pages (from-to)198-214
Number of pages17
JournalGenes and Cancer
Volume9
Issue number5-6
DOIs
StatePublished - May 1 2018

Fingerprint

docetaxel
Prostatic Neoplasms
Prostate
Neoplasms
Carcinogenesis
Epithelial-Mesenchymal Transition
Chromosome Mapping
Transcription Factor AP-1
Oncogenes
Cell Movement
Transcription Factors
Cell Line
Genes

Keywords

  • Chemotherapy resistance
  • ELF1
  • ETS
  • Prostate cancer
  • Tumor suppressor

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

Cite this

Common ELF1 deletion in prostate cancer bolsters oncogenic ets function, inhibits senescence and promotes docetaxel resistance. / Budka, Justin A.; Ferris, Mary W.; Capone, Matthew J.; Hollenhorst, Peter.

In: Genes and Cancer, Vol. 9, No. 5-6, 01.05.2018, p. 198-214.

Research output: Contribution to journalArticle

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