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Prostate. 2015 Jun;75(8):872-82. doi: 10.1002/pros.22970. Epub 2015 Mar 1.

Elf5 inhibits TGF-β-driven epithelial-mesenchymal transition in prostate cancer by repressing SMAD3 activation.

Author information

1
Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China.

Abstract

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.

KEYWORDS:

EMT; Elf5; TGF-β; prostate cancer

PMID:
25728398
DOI:
10.1002/pros.22970
[Indexed for MEDLINE]

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