View : 280 Download: 0

EW-7195, a novel inhibitor of ALK5 kinase inhibits EMT and breast cancer metastasis to lung

Title
EW-7195, a novel inhibitor of ALK5 kinase inhibits EMT and breast cancer metastasis to lung
Authors
Park C.-Y.Son J.-Y.Jin C.H.Nam J.-S.Kim D.-K.Sheen Y.Y.
Ewha Authors
신윤용김대기
SCOPUS Author ID
신윤용scopus; 김대기scopus
Issue Date
2011
Journal Title
European Journal of Cancer
ISSN
0959-8049JCR Link
Citation
European Journal of Cancer vol. 47, no. 17, pp. 2642 - 2653
Indexed
SCI; SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
Recently, researchers are actively pursuing efforts to develop potent and selective ALK5 (TβRI) kinase inhibitors for clinical development. In this study, the authors examined a novel small molecule inhibitor of ALK5, 3-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl) -1H-imidazol-2-yl)methylamino)benzonitrile (EW-7195) to determine if it has potential for cancer treatment. The inhibitory effects of EW-7195 on TGF-β-induced Smad signaling and epithelial-to-mesenchymal transition (EMT) were investigated in mammary epithelial cells using luciferase reporter assays, immunoblotting, confocal microscopy and wound healing assays. In addition, the suppressive effects of EW-7195 on mammary cancer metastasis to lung were examined using a Balb/c xenograft and MMTV/cNeu transgenic mice model system. The novel ALK5 inhibitor, EW-7195, inhibited the TGF-β 1- stimulated transcriptional activations of p3TP-Lux and pCAGA 12-Luc. In addition, EW-7195 decreased phosphorylated Smad2 levels and the nuclear translocation of Smad2 increased by TGF-β 1. In addition, EW-7195 inhibited TGF-β 1-induced EMT and wound healing of NMuMG cells. Furthermore, in xenografted Balb/c and MMTV/cNeu mice, EW-7195 inhibited metastasis to lung from breast tumours. The novel ALK5 inhibitor, EW-7195, efficiently inhibited TGF-β 1-induced Smad signaling, EMT and breast tumour metastasis to the lung in vivo, demonstrating that EW-7195 has therapeutic potential for the breast cancer metastasis to the lung. © 2011 Elsevier Ltd. All rights reserved.
Show the fulltext
DOI
10.1016/j.ejca.2011.07.007
Appears in Collections:
약학대학 > 약학과 > Journal papers
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE