title: 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.affiliation: Laboratory of Molecular and Cellular Biology, Department of Biology, Faculty of Natural Systems, Institute of Science and Engineering, Kanazawa University, Ishikawa, Japan. funasaka@staff.kanazawa-u.ac.jp
authors.forename: Tatsuyoshi
authors.initials: T
authors.lastname: Funasaka
authors.forename: Vitaly
authors.initials: V
authors.lastname: Balan
authors.forename: Avraham
authors.initials: A
authors.lastname: Raz
authors.forename: Richard W
authors.initials: RW
authors.lastname: Wong
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000235:genetics; D049109:Cell Proliferation; D018450:Disease Progression; D037502:Galectin 3 / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D028861:Nuclear Pore Complex Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D029543:Nucleocytoplasmic Transport Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D054730:Protein Interaction Domains and Motifs; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D051176:beta Catenin / Q000378:metabolism
chemical_list: C495270:CTNNB1 protein, human; D037502:Galectin 3; D028861:Nuclear Pore Complex Proteins; D029543:Nucleocytoplasmic Transport Proteins; C465451:Nup98 protein, human; D034741:RNA, Small Interfering; D051176:beta Catenin
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