title: Cell surface localization of importin α1/KPNA2 affects cancer cell proliferation by regulating FGF1 signalling.
abstract: Importin α1 is involved in nuclear import as a receptor for proteins with a classical nuclear localization signal (cNLS). Here, we report that importin α1 is localized to the cell surface in several cancer cell lines and detected in their cultured medium. We also found that exogenously added importin α1 is associated with the cell membrane via interaction with heparan sulfate. Furthermore, we revealed that the cell surface importin α1 recognizes cNLS-containing substrates. More particularly, importin α1 bound directly to FGF1 and FGF2, secreted cNLS-containing growth factors, and addition of exogenous importin α1 enhanced the activation of ERK1/2, downstream targets of FGF1 signalling, in FGF1-stimulated cancer cells. Additionally, anti-importin α1 antibody treatment suppressed the importin α1-FGF1 complex formation and ERK1/2 activation, resulting in decreased cell growth. This study provides novel evidence that functional importin α1 is located at the cell surface, where it accelerates the proliferation of cancer cells.
authors.affiliation: Laboratory of Nuclear Transport Dynamics, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.
authors.forename: Kohji
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Laboratory of Nuclear Transport Dynamics, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Miyamoto
authors.affiliation: Laboratory of Nuclear Transport Dynamics, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.|Department of Genetics, Graduate School of Medicine, Osaka University, 1-3 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Tsujii
authors.affiliation: Laboratory of Nuclear Transport Dynamics, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Moriyama
authors.affiliation: Laboratory of Nuclear Transport Dynamics, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.
authors.forename: Yudai
authors.initials: Y
authors.lastname: Ikuno
authors.affiliation: Laboratory of Proteome Research, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Shiromizu
authors.affiliation: Laboratory of Immune Signal, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Serada
authors.affiliation: Laboratory of Immune Signal, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Fujimoto
authors.affiliation: Laboratory of Proteome Research, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tomonaga
authors.affiliation: Laboratory of Immune Signal, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Naka
authors.affiliation: National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.|Laboratory of Biomedical Innovation, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka 567-0085, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yoneda
authors.affiliation: Laboratory of Nuclear Transport Dynamics, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.|Laboratory of Biomedical Innovation, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka 567-0085, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Oka
mesh_terms: D049109:Cell Proliferation; D016220:Fibroblast Growth Factor 1 / Q000235:genetics / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D020935:MAP Kinase Signaling System; D061986:MCF-7 Cells; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D028901:alpha Karyopherins / Q000235:genetics / Q000378:metabolism*
chemical_list: C490630:KPNA2 protein, human; D009363:Neoplasm Proteins; D028901:alpha Karyopherins; D016220:Fibroblast Growth Factor 1; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3