The epithelial-derived type II transmembrane serine protease epithin has been shown to be upregulated in a variety of cancer cell lines and tumor tissues, and its upregulation correlates well with tumor progression in many cases. However, little is known regarding the regulation of its expression and the mechanism of its roles in tumor progression. Here, we show that transforming growth factor-β (TGF-β), a potent inducer of epithelial-mesenchymal transition (EMT) in tumor progression, upregulates epithin, and that epithin plays a critical role in TGF-β-induced EMT. Forced overexpression of epithin induced EMT to exhibit characteristic morphological changes, alternations in EMT-related proteins and enhanced cell motility. Conversely, shRNA-mediated knockdown of endogenous epithin inhibited TGF-β-induced expression of mesenchymal markers and morphological changes. Furthermore, TGF-β-induced cell migration and invasion were significantly impaired by epithin knockdown. In addition, we demonstrate that TGF-β upregulates epithin transcriptionally via the Smad2/Smad4-mediated pathway. These results suggest that epithin is a key mediator of TGF-β-induced EMT in tumor progression.
|Number of pages||7|
|Journal||Biochemical and biophysical research communications|
|Publication status||Published - 2010 May 14|
Bibliographical noteFunding Information:
This work was supported by KOSEF grant R01-2007-000-20275-0 funded by the Korea government to D. Park, and the BioDiscovery Research Program 34689-1 grant from the MST and the Korea Research Foundation Grant by MOEHRD ( KRF-2006-34673-1 ) to M. Kim.
- Epithelial-mesenchymal transition
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology