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BMC Cancer
Published in: BMC Cancer 1/2023

Open Access 01-12-2023 | Research

Endosulfine alpha maintains spindle pole integrity by recruiting Aurora A during mitosis

Authors: Seul Kim, Kyoungho Jun, Ye-Hyun Kim, Kwan-Young Jung, Jeong Su Oh, Jae-Sung Kim

Published in: BMC Cancer | Issue 1/2023

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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.
Appendix
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Metadata
Title
Endosulfine alpha maintains spindle pole integrity by recruiting Aurora A during mitosis
Authors
Seul Kim
Kyoungho Jun
Ye-Hyun Kim
Kwan-Young Jung
Jeong Su Oh
Jae-Sung Kim
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2023
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-023-11742-0

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