A lignan induces lysosomal dependent degradation of FoxM1 protein tosuppress beta-catenin nuclear translocation

Collection with item attached
2017
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/473685.do
DOI
10.1038/srep45951
Title
A lignan induces lysosomal dependent degradation of FoxM1 protein tosuppress beta-catenin nuclear translocation
Description
This study was supported by the National Research Foundation of Korea(NRF) Grant funded by the Korean Government (MSIP) (No. 2011-0030074).We thank prof. Sung Won Kwon (S.N.U.) for measuring high resolution massspectra.
abstract
Colon cancer is one of the most common cancers. In this study, we isolated a lignan [(-)-(2R, 3R)-1,4O-diferuloylsecoisolariciresinol, DFS] from Alnus japonica (Betulaceae) and investigated its biological activity and mechanism of action on colon cancer. DFS reduced the viability of colon cancer cells and induced cell cycle arrest. DFS also suppressed beta-catenin nuclear translocation and beta-catenin target gene expression through a reduction in FoxM1 protein. To assess the mechanism of the action of DFS, we investigated the effect of DFS on endogenous and exogenous FoxM1 protein degradation in colon cancer cells. DFS-induced FoxM1 protein degradation was suppressed by lysosomal inhibitors, chloroquine and bafilomycin A1, but not by knock-down of proteasomal proteins. The mechanism of DFS for FoxM1 degradation is lysosomal dependent, which was not reported before. Furthermore, we found that FoxM1 degradation was partially lysosomal-dependent under normal conditions. These observations indicate that DFS from A. japonica suppresses colon cancer cell proliferation by reducing beta-catenin nuclear translocation. DFS induces lysosomal-dependent FoxM1 protein degradation. This is the first report on the lysosomal degradation of FoxM1 by a small molecule. DFS may be useful in treating cancers that feature the elevated expression of FoxM1.
provenance
Made available in Cube on 2018-09-28T10:26:10Z (GMT). No. of bitstreams: 0
language
English
author
Dong, Guang-zhi
Jeong, Ji Hye
Lee, Yu-ih
Han, Yeong Eun
Shin, Jung Sook
Kim, Yoon-Jung
Jeon, Raok
Kim, Young Hwa
Park, Tae Jun
Il Kim, Keun
Ryu, Jae-Ha
accessioned
2018-09-28T10:26:10Z
available
2018-09-28T10:26:10Z
issued
2017
citation
SCIENTIFIC REPORTS(7)
issn
2045-2322
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/473685.do
Funder
교육부
Funding Program
BK21플러스사업(0.5)
Project ID
1345274087
Jurisdiction
Rep.of Korea
Project Name
Research Center for Biomedical Sciences
rights
openAccess
type
article


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