Endosulfine alpha maintains spindle pole integrity by recruiting Aurora A during mitosis
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...
| Main Authors: | , , , , , |
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| Format: | Article |
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BMC
2023-12-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-023-11742-0 |
| _version_ | 1797376887029235712 |
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| author | Seul Kim Kyoungho Jun Ye-Hyun Kim Kwan-Young Jung Jeong Su Oh Jae-Sung Kim |
| author_facet | Seul Kim Kyoungho Jun Ye-Hyun Kim Kwan-Young Jung Jeong Su Oh Jae-Sung Kim |
| author_sort | Seul Kim |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T19:46:03Z |
| format | Article |
| id | doaj.art-082b81eb6ac24244bbc199a385ff893b |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-03-08T19:46:03Z |
| publishDate | 2023-12-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-082b81eb6ac24244bbc199a385ff893b2023-12-24T12:21:44ZengBMCBMC Cancer1471-24072023-12-0123111410.1186/s12885-023-11742-0Endosulfine alpha maintains spindle pole integrity by recruiting Aurora A during mitosisSeul Kim0Kyoungho Jun1Ye-Hyun Kim2Kwan-Young Jung3Jeong Su Oh4Jae-Sung Kim5Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical SciencesDivision of Radiation Biomedical Research, Korea Institute of Radiological and Medical SciencesDivision of Radiation Biomedical Research, Korea Institute of Radiological and Medical SciencesTherapeutics & Biotechnology Division, Korea Research Institute of Chemical TechnologyDepartment of Integrative Biotechnology, Sungkyunkwan UniversityDivision of Radiation Biomedical Research, Korea Institute of Radiological and Medical SciencesAbstract 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.https://doi.org/10.1186/s12885-023-11742-0ENSAMitosisSpindle pole integrityMASTLAurora A |
| spellingShingle | Seul Kim Kyoungho Jun Ye-Hyun Kim Kwan-Young Jung Jeong Su Oh Jae-Sung Kim Endosulfine alpha maintains spindle pole integrity by recruiting Aurora A during mitosis BMC Cancer ENSA Mitosis Spindle pole integrity MASTL Aurora A |
| title | Endosulfine alpha maintains spindle pole integrity by recruiting Aurora A during mitosis |
| title_full | Endosulfine alpha maintains spindle pole integrity by recruiting Aurora A during mitosis |
| title_fullStr | Endosulfine alpha maintains spindle pole integrity by recruiting Aurora A during mitosis |
| title_full_unstemmed | Endosulfine alpha maintains spindle pole integrity by recruiting Aurora A during mitosis |
| title_short | Endosulfine alpha maintains spindle pole integrity by recruiting Aurora A during mitosis |
| title_sort | endosulfine alpha maintains spindle pole integrity by recruiting aurora a during mitosis |
| topic | ENSA Mitosis Spindle pole integrity MASTL Aurora A |
| url | https://doi.org/10.1186/s12885-023-11742-0 |
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