期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 434, 期 1, 页码 155-161出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2013.03.052
关键词
Nucleoporin; Nuclear pore complex; Galectin-3; Nuclear transport; Cancer progression
资金
- MEXT [23701049, 23310151]
- National Institute of Health [R37CA46120]
- Takeda Science Foundation
- Grants-in-Aid for Scientific Research [24650611, 23310151, 24121710, 23701049] Funding Source: KAKEN
Nucleoporin Nup98 is a component of the nuclear pore complex, and is important in transport across the nuclear pore. Many studies implicate nucleoporin in cancer progression, but no direct mechanistic studies of its effect in cancer have been reported. We show here that Nup98 specifically regulates nucleus cytoplasm transport of galectin-3, which is a beta-galactoside-binding protein that affects adhesion, migration, and cancer progression, and controls cell growth through the beta-catenin signaling pathway in cancer cells. Nup98 interacted with galectin-3 on the nuclear membrane, and promoted galectin-3 cytoplasmic translocation whereas other nucleoporins did not show these functions. Inversely, silencing of Nup98 expression by siRNA technique localized galectin-3 to the nucleus and retarded cell growth, which was rescued by Nup98 transfection. In addition, Nup98 RNA interference significantly suppressed downstream mRNA expression in the beta-catenin pathway, such as cyclin D1 and FRA-1, while nuclear galectin-3 binds to beta-catenin to inhibit transcriptional activity. Reduced expression of beta-catenin target genes is consistent with the Nup98 reduction and the galectin-3 nucleus translocation rate. Overall, the results show Nup98's involvement in nuclear cytoplasm translocation of galectin-3 and beta-catenin signaling pathway in regulating cell proliferation, and the results depicted here suggest a novel therapeutic target/modality for cancers. (C) 2013 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据