論文 - 詳細
| RRC ID | 37892 |
|---|---|
| 著者 | Yoshino Y, Ishioka C. |
| タイトル | Inhibition of glycogen synthase kinase-3 beta induces apoptosis and mitotic catastrophe by disrupting centrosome regulation in cancer cells. |
| ジャーナル | Sci Rep |
| Abstract |
Glycogen synthase kinase-3 beta (GSK-3β) has been investigated as a therapeutic target for numerous human diseases including cancer because of their diverse cellular functions. Although GSK-3β inhibitors have been investigated as anticancer reagents, precise biological mechanisms remain to be determined. In this study, we investigated the anticancer effects of GSK-3β inhibitors on cancer cell lines and observed centrosome dysregulation which resulted in abnormal mitosis. Mitotic checkpoints sensed the mitotic abnormalities and induced apoptosis. For cells that were inherently resistant to apoptosis, cell death distinct from apoptosis was induced. After GSK-3β inhibitor treatment, these cells exhibited characteristic features of mitotic catastrophe, including distended and multivesiculated nuclei and inappropriate reductions in cyclin B1 expression. This suggested that mitotic catastrophe was an alternative mechanism in cells resistant to apoptosis. Although the role of GSK-3β in centrosomes has not yet been clarified, phosphorylated GSK-3β was localised in centrosomes. From these data, GSK-3β seems to regulate centrosome function. Thus, we propose that centrosome dysregulation is an important mechanism for the anticancer effects of GSK-3β inhibitors and that mitotic catastrophe serves as a safe-guard system to remove cells with any mitotic abnormalities induced by GSK-3β inhibition. |
| 巻・号 | 5 |
| ページ | 13249 |
| 公開日 | 2015-8-21 |
| DOI | 10.1038/srep13249 |
| PII | srep13249 |
| PMID | 26292722 |
| PMC | PMC4543981 |
| MeSH | Apoptosis / drug effects* Cell Cycle / drug effects Cell Line, Tumor Cell Proliferation / drug effects Cell Survival / drug effects Centrosome / drug effects Centrosome / metabolism* Chromosomal Instability / drug effects Down-Regulation / drug effects Glycogen Synthase Kinase 3 / antagonists & inhibitors* Glycogen Synthase Kinase 3 / metabolism Glycogen Synthase Kinase 3 beta Humans Mitosis / drug effects* NF-kappa B / metabolism Neoplasms / enzymology* Neoplasms / pathology* Phosphatidylinositol 3-Kinases / metabolism Protein Kinase Inhibitors / pharmacology* Proto-Oncogene Proteins c-akt / metabolism Signal Transduction / drug effects Spindle Apparatus / drug effects Spindle Apparatus / metabolism Thiazoles / pharmacology Urea / analogs & derivatives Urea / pharmacology |
| IF | 3.998 |
| 引用数 | 25 |
| WOS 分野 | MULTIDISCIPLINARY SCIENCES |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | MIA Paca2(RCB2094) |