Nucleoporin Nup98 mediates galectin-3 nuclear-cytoplasmic trafficking.

Abstract

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 ß-galactoside-binding protein that affects adhesion, migration, and cancer progression, and controls cell growth through the ß-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 ß-catenin pathway, such as cyclin D1 and FRA-1, while nuclear galectin-3 binds to ß-catenin to inhibit transcriptional activity. Reduced expression of ß-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 ß-catenin signaling pathway in regulating cell proliferation, and the results depicted here suggest a novel therapeutic target/modality for cancers.

• Authors: Tatsuyoshi Funasaka, Vitaly Balan, Avraham Raz, Richard W Wong
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 434 Issue 1 Pg. 155-61 (Apr 26 2013) ISSN: 1090-2104 [Electronic] United States
• PMID: 23541576 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• CTNNB1 protein, human
• Galectin 3
• Nuclear Pore Complex Proteins
• Nucleocytoplasmic Transport Proteins
• Nup98 protein, human
• RNA, Small Interfering
• beta Catenin

Topics

• Active Transport, Cell Nucleus (genetics)
• Cell Proliferation
• Disease Progression
• Galectin 3 (metabolism)
• HeLa Cells
• Humans
• MCF-7 Cells
• Neoplasms (metabolism, pathology)
• Nuclear Pore Complex Proteins (antagonists & inhibitors, genetics, physiology)
• Nucleocytoplasmic Transport Proteins (genetics, metabolism, physiology)
• Protein Interaction Domains and Motifs
• RNA, Small Interfering (genetics)
• Signal Transduction
• beta Catenin (metabolism)