title: Nuclear accumulation of annexin A2 contributes to chromosomal instability by coilin-mediated centromere damage.
abstract: Most human cancers show chromosomal instability (CIN), but the precise mechanisms remain uncertain. Annexin A2 is frequently overexpressed in human cancers, and its relationship to tumorigenesis is poorly understood. We found that annexin A2 is overexpressed in the nuclei of CIN cells compared with cells with microsatellite instability (MIN). Ectopic annexin A2 expression in MIN cells results in a high level of aneuploidy and induces lagging chromosomes; suppression of annexin A2 in CIN cells reduces such CIN signatures with apoptosis of highly aneuploid cells. Ectopic expression of annexin A2 in MIN cells reduces the expression of centromere proteins. Conversely, annexin A2-knockdown in CIN cells increases the expression of centromere proteins. Moreover, the endogenous expression levels of centromere proteins in CIN cells were greatly reduced compared with MIN cell lines. The reduced expression of centromere proteins likely occurred due to aberrant centromere localization of coilin, a major component of the Cajal bodies. These results suggest that nuclear accumulation of annexin A2 has a crucial role in CIN by disrupting centromere function.
authors.affiliation: Department of Molecular Diagnosis (F8), Graduate School of Medicine, Chiba University, Inohana, Chuo-ku, Chiba, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kazami
authors.affiliation: Department of Molecular Diagnosis (F8), Graduate School of Medicine, Chiba University, Inohana, Chuo-ku, Chiba, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nie
authors.affiliation: Department of Molecular Diagnosis (F8), Graduate School of Medicine, Chiba University, Inohana, Chuo-ku, Chiba, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Satoh
authors.affiliation: Laboratory of Proteome Research, National Institute of Biomedical Innovation, Saito-Asagi, Ibaraki City, Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kuga
authors.affiliation: Department of Molecular Diagnosis (F8), Graduate School of Medicine, Chiba University, Inohana, Chuo-ku, Chiba, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Matsushita
authors.affiliation: 1] Department of Molecular Diagnosis (F8), Graduate School of Medicine, Chiba University, Inohana, Chuo-ku, Chiba, Japan [2] Laboratory of Proteome Research, National Institute of Biomedical Innovation, Saito-Asagi, Ibaraki City, Osaka, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Kawasaki
authors.affiliation: 1] Department of Molecular Diagnosis (F8), Graduate School of Medicine, Chiba University, Inohana, Chuo-ku, Chiba, Japan [2] Laboratory of Proteome Research, National Institute of Biomedical Innovation, Saito-Asagi, Ibaraki City, Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tomonaga
authors.affiliation: Department of Molecular Diagnosis (F8), Graduate School of Medicine, Chiba University, Inohana, Chuo-ku, Chiba, Japan.
authors.forename: F
authors.initials: F
authors.lastname: Nomura
mesh_terms: D000782:Aneuploidy; D017306:Annexin A2 / Q000235:genetics* / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002503:Centromere / Q000235:genetics* / Q000378:metabolism; D000076247:Centromere Protein A; D043171:Chromosomal Instability; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D053842:Microsatellite Instability; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D020543:Proteome / Q000235:genetics / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017306:Annexin A2; D001324:Autoantigens; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone; D009687:Nuclear Proteins; D020543:Proteome; C060905:centromere protein C; C068921:p80-coilin