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Elf5 inhibits TGF‐β‐driven epithelial‐mesenchymal transition in prostate cancer by repressing SMAD3 activation
Author(s) -
Yao Bing,
Zhao Jinsheng,
Li Yalin,
Li Hui,
Hu Zhaojun,
Pan Pan,
Zhang Yiran,
Du E.,
Liu Ranlu,
Xu Yong
Publication year - 2015
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.22970
Subject(s) - epithelial–mesenchymal transition , prostate cancer , cancer research , transforming growth factor , metastasis , lncap , tumor progression , medicine , cancer
BACKGROUND The epithelial‐mesenchymal transition (EMT) has been associated with the acquisition of migration, invasiveness, and metastasis traits. During tumor progression, EMT can be induced by transforming growth factor‐β (TGF‐β) signal that epithelial cells receive from their microenvironment. However, the master regulatory controls on TGF‐β‐EMT axis are not understood. METHODS The protein expression in human specimens was measured by immunohistochemical staining. E74‐like factor 5 (Elf5) was silenced by short interfering RNAs in LNCaP cells and stably overexpressed by HA‐tagged Elf5 cDNAs in 22Rv1 cells. These cells were used to study migration and anchorage‐independent growth. RESULTS Our data reveal that Elf5 results in the failure of mesenchymal morphogenesis, upregulation of EMT markers, spheres formation, and migration in the presence of TGF‐β. Furthermore, Elf5 blocks TGF‐β signaling, through decreasing drosophila mothers against decapentaplegic protein (SMAD3) activation by binding to it, one of the major effector of TGF‐β‐induced EMT. Moreover, Elf5 can serve as a prognostic marker of metastasis‐free survival in patients with TGF‐β‐positive prostate cancer. CONCLUSIONS Elf5 expression is inversely correlated with EMT. Elf5 inhibits TGF‐β‐driven EMT via repressing SMAD3 phosphorylation in prostate cancer cells. In addition, Elf5 can be used as a biomarker of metastasis‐free survival in patients with TGF‐β‐positive prostate cancer. Prostate 75:872–882, 2015 . © 2015 Wiley Periodicals, Inc.