title: A role of fukutin, a gene responsible for Fukuyama type congenital muscular dystrophy, in cancer cells: a possible role to suppress cell proliferation.
abstract: Fukutin, a gene responsible for Fukuyama type congenital muscular dystrophy (FCMD), is presumably related to the glycosylation of alpha-dystroglycan (alpha-DG), involved in basement membrane formation. Hypoglycosylation of alpha-DG plays a key role for the pathogenesis of FCMD. On the other hand, fukutin and alpha-DG are also expressed in various non-neuromuscular tissues. Recently, a role of alpha-DG as a cancer suppressor has been proposed, because of a decrease of glycosylated alpha-DG in cancers. In this study, function of fukutin was investigated in two cancer cell lines, focusing on whether fukutin is involved in the glycosylation of alpha-DG in cancer cells and has any possible roles related to a cancer suppressor. Localization of fukutin and a result of laminin-binding assay after RNA interference suggest that fukutin may be involved in the glycosylation of alpha-DG in a small portion in these cancer cell lines. In Western blotting and immuno-electron microscopy, localization of fukutin in the nucleus was suggested in addition to the Golgi apparatus and/or endoplasmic reticulum. Immunohistochemically, there were more Ki-67-positive cells and more nuclear staining of phosphorylated c-jun after knockdown of fukutin in two cell lines. Fukutin appears to suppress cell proliferation through a system involving c-jun, although it is unclear this process is related to alpha-DG or not at present. The result may propose a possibility of another function of fukutin in addition to the glycosylation of alpha-DG in cancer cells.
authors.affiliation: Department of Pathology, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan. sheto@research.twmu.ac.jp
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Kato
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Shibata
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Sawada
authors.forename: Makiko
authors.initials: M
authors.lastname: Osawa
authors.forename: Makio
authors.initials: M
authors.lastname: Kobayashi
mesh_terms: D015153:Blotting, Western / Q000379:methods; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D049030:Dystroglycans / Q000378:metabolism; D006031:Glycosylation; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D016253:Microscopy, Immunoelectron; D009136:Muscular Dystrophies / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology
chemical_list: C113587:FKTN protein, human; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D049030:Dystroglycans