Elf5 inhibits TGF-β-driven epithelial-mesenchymal transition in prostate cancer by repressing SMAD3 activation.
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.
Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China.
Bing
B
Yao
Jinsheng
J
Zhao
Yalin
Y
Li
Hui
H
Li
Zhaojun
Z
Hu
Pan
P
Pan
Yiran
Y
Zhang
E
E
Du
Ranlu
R
Liu
Yong
Y
Xu
D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005500:Follow-Up Studies; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D050783:Proto-Oncogene Proteins c-ets / Q000096:biosynthesis*; D051900:Smad3 Protein / Q000378:metabolism*; D014157:Transcription Factors; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000378:metabolism*
D004268:DNA-Binding Proteins; C116038:ELF5 protein, human; D050783:Proto-Oncogene Proteins c-ets; C497790:SMAD3 protein, human; D051900:Smad3 Protein; D014157:Transcription Factors; D016212:Transforming Growth Factor beta
EMT; Elf5; TGF-β; prostate cancer