ETS transcription factor ESE1/ELF3 orchestrates a positive feedback loop that constitutively activates NF-κB and drives prostate cancer progression

Nicole Longoni, Manuela Sarti, Domenico Albino, Gianluca Civenni, Anastasia Malek, Erica Ortelli, Sandra Pinton, Maurizia Mello-Grand, Paola Ostano, Gioacchino D'Ambrosio, Fausto Sessa, Ramon Garcia-Escudero, George N. Thalmann, Giovanna Chiorino, Carlo V. Catapano, Giuseppina M. Carbone

Research output: Contribution to journalArticle

Abstract

Chromosomal translocations leading to deregulated expression of ETS transcription factors are frequent in prostate tumors. Here, we report a novel mechanism leading to oncogenic activation of the ETS factor ESE1/ELF3 in prostate tumors. ESE1/ELF3 was overexpressed in human primary and metastatic tumors. It mediated transforming phenotypes in vitro and in vivo and induced an inflammatory transcriptome with changes in relevant oncogenic pathways. ESE1/ELF3 was induced by interleukin (IL)-1β through NF-kB and was a crucial mediator of the phenotypic and transcriptional changes induced by IL-1β in prostate cancer cells. This linkage was mediated by interaction of ESE1/ELF3 with the NF-κB subunits p65 and p50, acting by enhancing their nuclear translocation and transcriptional activity and by inducing p50 transcription. Supporting these findings, gene expression profiling revealed an enrichment of NF-kB effector functions in prostate cancer cells or tumors expressing high levels of ESE1/ELF3. We observed concordant upregulation of ESE1/ELF3 and NF-κB in human prostate tumors that was associated with adverse prognosis. Collectively, our results define an important new mechanistic link between inflammatory signaling and the progression of prostate cancer.

Original languageEnglish
Pages (from-to)4533-4547
Number of pages15
JournalCancer Research
Volume73
Issue number14
DOIs
Publication statusPublished - Jul 15 2013

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Longoni, N., Sarti, M., Albino, D., Civenni, G., Malek, A., Ortelli, E., Pinton, S., Mello-Grand, M., Ostano, P., D'Ambrosio, G., Sessa, F., Garcia-Escudero, R., Thalmann, G. N., Chiorino, G., Catapano, C. V., & Carbone, G. M. (2013). ETS transcription factor ESE1/ELF3 orchestrates a positive feedback loop that constitutively activates NF-κB and drives prostate cancer progression. Cancer Research, 73(14), 4533-4547. https://doi.org/10.1158/0008-5472.CAN-12-4537