title: Lamin B2 prevents chromosome instability by ensuring proper mitotic chromosome segregation.
abstract: The majority of human cancer shows chromosomal instability (CIN). Although the precise mechanism remains largely uncertain, proper progression of mitosis is crucial. B-type lamins were suggested to be components of the spindle matrix of mitotic cells and to be involved in mitotic spindle assembly; thus, B-type lamins may contribute to the maintenance of chromosome integrity. Here, using a proteomic approach, we identified lamin B2 as a novel protein involved in CIN. Lamin B2 expression decreased in colorectal cancer cell lines exhibiting CIN, as compared with colorectal cancer cell lines exhibiting microsatellite instability (MIN), which is mutually exclusive to CIN. Importantly, lamin B2 knockdown in MIN-type colorectal cancer cells induced CIN phenotypes such as aneuploidy, chromosome mis-segregation and aberrant spindle assembly, whereas ectopic expression of lamin B2 in CIN-type colorectal cancer cells prevented their CIN phenotypes. Additionally, immunohistochemical analysis showed a lower expression of lamin B2 in cancer tissues extracted from patients with sporadic colorectal cancer (CIN-type) than that from patients with hereditary non-polyposis colorectal cancer (HNPCC; MIN type). Intriguingly, mitotic lamin B2 in MIN cancer cells was localized outside the spindle poles and mitotic lamin B2 localization was diminished in CIN cancer cells, suggesting an important role of lamin B2 in proper mitotic spindle formation. The obtained results suggest that lamin B2 maintains chromosome integrity by ensuring proper spindle assembly and that its downregulation causes CIN in colorectal cancer.
authors.affiliation: 1] Laboratory of Proteome Research, National Institute of Biomedical Innovation, Osaka, Japan [2] Department of Molecular Diagnosis (F8), Graduate School of Medicine, Chiba University, Chiba, Japan [3] Department of Biochemistry and Molecular Biology, Kyoto Pharmaceutical University, Kyoto, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kuga
authors.affiliation: Department of Molecular Diagnosis (F8), Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nie
authors.affiliation: Department of Molecular Diagnosis (F8), Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kazami
authors.affiliation: Department of Molecular Diagnosis (F8), Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Satoh
authors.affiliation: Department of Molecular Diagnosis (F8), Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Matsushita
authors.affiliation: Department of Molecular Diagnosis (F8), Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: F
authors.initials: F
authors.lastname: Nomura
authors.affiliation: Biological Macromolecules Laboratory, Structural Biology Center, National Institute of Genetics, Shizuoka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Maeshima
authors.affiliation: Department of Biochemistry and Molecular Biology, Kyoto Pharmaceutical University, Kyoto, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Nakayama
authors.affiliation: 1] Laboratory of Proteome Research, National Institute of Biomedical Innovation, Osaka, Japan [2] Department of Molecular Diagnosis (F8), Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tomonaga