ESE3/EHF controls epithelial cell differentiation and its loss leads to prostate tumors with mesenchymal and stem-like features

Domenico Albino, Nicole Longoni, Laura Curti, Maurizia Mello-Grand, Sandra Pinton, Gianluca Civenni, George Thalmann, Gioacchino D'Ambrosio, Manuela Sarti, Fausto Sessa, Giovanna Chiorino, Carlo V. Catapano, Giuseppina M. Carbone

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Cancer stem cells (CSC) play a significant role in tumor progression, disease recurrence, and treatment failure. Here, we show that the endogenously expressed ETS transcription factor ESE3/EHF controls prostate epithelial cell differentiation and stem-like potential. We found that loss of ESE3/EHF induced epithelial-to-mesenchymal transition (EMT), stem-like features, and tumor-initiating and metastatic properties in prostate epithelial cells, and reexpression of ESE3/EHF inhibited the stem-like properties and tumorigenic potential of prostate cancer cells. Mechanistically, ESE3/EHF repressed the expression of key EMT and CSC genes, including TWIST1, ZEB2, BMI1, and POU5F1. Analysis of human tissue microarrays showed that reduced ESE3/EHF expression is an early event in tumorigenesis, frequently occurring independently of other ETS gene alterations. Additional analyses linked loss of ESE3/EHF expression to a distinct group of prostate tumors with distinctive molecular and biologic characteristics, including increased expression of EMT and CSC genes. Low ESE3/EHF expression was also associated with increased biochemical recurrence of prostate cancer and reduced overall survival after prostatectomy. Collectively, our findings define a key role for ESE3/EHF in the development of a subset of prostate tumors and highlight the clinical importance of identifying molecularly defined tumor subgroups.

Original languageEnglish
Pages (from-to)2889-2900
Number of pages12
JournalCancer Research
Volume72
Issue number11
DOIs
Publication statusPublished - Jun 1 2012

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Prostate
Cell Differentiation
Epithelial Cells
Epithelial-Mesenchymal Transition
Neoplastic Stem Cells
Neoplasms
Mesenchymal Stromal Cells
Prostatic Neoplasms
Tissue Array Analysis
Genes
Recurrence
Prostatectomy
Treatment Failure
Disease Progression
Carcinogenesis
Transcription Factors
Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Albino, D., Longoni, N., Curti, L., Mello-Grand, M., Pinton, S., Civenni, G., ... Carbone, G. M. (2012). ESE3/EHF controls epithelial cell differentiation and its loss leads to prostate tumors with mesenchymal and stem-like features. Cancer Research, 72(11), 2889-2900. https://doi.org/10.1158/0008-5472.CAN-12-0212

ESE3/EHF controls epithelial cell differentiation and its loss leads to prostate tumors with mesenchymal and stem-like features. / Albino, Domenico; Longoni, Nicole; Curti, Laura; Mello-Grand, Maurizia; Pinton, Sandra; Civenni, Gianluca; Thalmann, George; D'Ambrosio, Gioacchino; Sarti, Manuela; Sessa, Fausto; Chiorino, Giovanna; Catapano, Carlo V.; Carbone, Giuseppina M.

In: Cancer Research, Vol. 72, No. 11, 01.06.2012, p. 2889-2900.

Research output: Contribution to journalArticle

Albino, D, Longoni, N, Curti, L, Mello-Grand, M, Pinton, S, Civenni, G, Thalmann, G, D'Ambrosio, G, Sarti, M, Sessa, F, Chiorino, G, Catapano, CV & Carbone, GM 2012, 'ESE3/EHF controls epithelial cell differentiation and its loss leads to prostate tumors with mesenchymal and stem-like features', Cancer Research, vol. 72, no. 11, pp. 2889-2900. https://doi.org/10.1158/0008-5472.CAN-12-0212
Albino, Domenico ; Longoni, Nicole ; Curti, Laura ; Mello-Grand, Maurizia ; Pinton, Sandra ; Civenni, Gianluca ; Thalmann, George ; D'Ambrosio, Gioacchino ; Sarti, Manuela ; Sessa, Fausto ; Chiorino, Giovanna ; Catapano, Carlo V. ; Carbone, Giuseppina M. / ESE3/EHF controls epithelial cell differentiation and its loss leads to prostate tumors with mesenchymal and stem-like features. In: Cancer Research. 2012 ; Vol. 72, No. 11. pp. 2889-2900.
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