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.
Written by:
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. Are you the author?
Institute of Oncology Research (IOR) and Oncology Institute of Southern Switzerland (IOSI), Bellinzona, Switzerland; Laboratory of Cancer Genomics, Fondazione Edo ed Elvo Tempia Valenta, Biella; IRCCS Multimedica, Milan; Department of Pathology University of Insubria, Varese, Italy; and Urology Research Laboratory, Department of Urology, University of Bern, Inselspital, Bern, Switzerland.
Reference: Cancer Res. 2012 Jun 1;72(11):2889-900.
doi: 10.1158/0008-5472.CAN-12-0212
PubMed Abstract
PMID: 22505649
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