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 language | English |
|---|---|
| Pages (from-to) | 2889-2900 |
| Number of pages | 12 |
| Journal | Cancer Research |
| Volume | 72 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Jun 1 2012 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
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 journal › Article
}
TY - JOUR
T1 - ESE3/EHF controls epithelial cell differentiation and its loss leads to prostate tumors with mesenchymal and stem-like features
AU - Albino, Domenico
AU - Longoni, Nicole
AU - Curti, Laura
AU - Mello-Grand, Maurizia
AU - Pinton, Sandra
AU - Civenni, Gianluca
AU - Thalmann, George
AU - D'Ambrosio, Gioacchino
AU - Sarti, Manuela
AU - Sessa, Fausto
AU - Chiorino, Giovanna
AU - Catapano, Carlo V.
AU - Carbone, Giuseppina M.
PY - 2012/6/1
Y1 - 2012/6/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84861903355&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84861903355&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-12-0212
DO - 10.1158/0008-5472.CAN-12-0212
M3 - Article
VL - 72
SP - 2889
EP - 2900
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 11
ER -