論文 - 詳細
| RRC ID | 78307 |
|---|---|
| 著者 | Kim S, Jun K, Kim YH, Jung KY, Oh JS, Kim JS. |
| タイトル | Endosulfine alpha maintains spindle pole integrity by recruiting Aurora A during mitosis. |
| ジャーナル | BMC Cancer |
| Abstract |
BACKGROUND:The maintenance of spindle pole integrity is essential for spindle assembly and chromosome segregation during mitosis. However, the underlying mechanisms governing spindle pole integrity remain unclear. METHODS:ENSA was inhibited by siRNA or MKI-2 treatment and its effect on cell cycle progression, chromosome alignment and microtubule alignment was observed by immunohistochemical staining and western blotting. PP2A-B55α knockdown by siRNA was performed to rescue the phenotype caused by ENSA inhibition. The interaction between ENSA and Aurora A was detected by in situ PLA. Furthermore, orthotopic implantation of 4Tl-luc cancer cells was conducted to confirm the consistency between the in vitro and in vivo relationship of the ENSA-Aurora A interaction. RESULTS:During mitosis, p-ENSA is localized at the spindle poles, and the inhibition of ENSA results in mitotic defects, such as misaligned chromosomes, multipolar spindles, asymmetric bipolar spindles, and centrosome defects, with a delay in mitotic progression. Although the mitotic delay caused by ENSA inhibition was rescued by PP2A-B55α depletion, spindle pole defects persisted. Notably, we observed a interaction between ENSA and Aurora A during mitosis, and inhibition of ENSA reduced Aurora A expression at the mitotic spindle poles. Injecting MKI-2-sensitized tumors led to increased chromosomal instability and downregulation of the MASTL-ENSA-Aurora A pathway in an orthotopic breast cancer mouse model. CONCLUSIONS:These findings provide novel insights into the regulation of spindle pole integrity by the MASTL-ENSA-Aurora A pathway during mitosis, highlighting the significance of ENSA in recruiting Aurora A to the spindle pole, independent of PP2A-B55α. |
| 巻・号 | 23(1) |
| ページ | 1263 |
| 公開日 | 2023-12-21 |
| DOI | 10.1186/s12885-023-11742-0 |
| PII | 10.1186/s12885-023-11742-0 |
| PMID | 38129815 |
| PMC | PMC10734108 |
| MeSH | Animals Centrosome / metabolism Mice Mitosis RNA, Small Interfering / metabolism Spindle Apparatus* / metabolism Spindle Poles* / metabolism |
| リソース情報 | |
| ヒト・動物細胞 | HeLa/Fucci(RCB2812) |