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Updated: Jan 5, 2026

Live Cell Imaging to Assess the Dynamics of Metaphase Timing and Cell Fate Following Mitotic Spindle Perturbations
Published on: September 20, 2019
The LIV-1-GRPEL1 axis adjusts cell fate during anti-mitotic agent-damaged mitosis
Pingbo Chen1, Beibei Wang1, Qingqing Mo1
1Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
Background:
Understanding how cells respond to mitotic poisons is of great biomedical and clinical significance. However, it remains unknown how cell-death or survival is determined during exposure to anti-mitotic drugs.
Methods:
The biological effects of SLC39A6 (LIV-1) and GrpE-like 1 (GRPEL1) on mitotic exit and apoptosis were evaluated both in vitro and in vivo using flow cytometry, western blotting, xenografts and time-lapse imaging. The interactions between proteins and the ubiquitination of GRPEL1 were assessed by GST pull down, immunoprecipitation and mass spectrometry analysis. The expression of LIV-1 in cancers was assessed by immunohistochemistry.
Findings:
Overexpression of LIV-1 led to direct apoptosis. Depleted for LIV-1 evade anti-mitotic agent-induced killing through a rapid exit from arrested mitosis. LIV-1 interacts with GRPEL1 and Stabilizes GRPEL1 Protein by Preventing Ubiquitylation of GRPEL1. LIV-1-GRPEL1 axis depletion works to reduce the mitotic arrest by inducing PP2A-B55α phosphates activity, while inhibit apoptosis by banding AIF and preventing the latter's release into the nucleus. Loss of function in this axis was frequent in multiple types of human epithelial cancer.
Interpretation:
These data demonstrate that LIV-1-GRPEL1 axis dually regulates mitotic exit as well as apoptosis by interacting with PP2A B55α and AIF. Its discovery constitutes a conceptual advance for the decisive mechanism of cell fate during damaged mitosis. FUND: National Clinical Research Center for Obstetric and Gynecologic Diseases, the National Natural Science Foundation of China.
Insights
The LIV-1-GRPEL1 axis controls cell death or survival during mitotic arrest. This axis regulates mitotic exit and apoptosis, offering new insights into cell fate mechanisms in cancer.
Area of Science:
- Cell Biology
- Molecular Oncology
- Cancer Therapeutics
Background:
- Cellular response to mitotic poisons is critical for cancer treatment.
- Mechanisms determining cell death versus survival during anti-mitotic drug exposure are largely unknown.
Purpose of the Study:
- To elucidate the roles of SLC39A6 (LIV-1) and GrpE-like 1 (GRPEL1) in regulating mitotic exit and apoptosis.
- To investigate the LIV-1-GRPEL1 axis in the context of anti-mitotic drug response and cancer.
Main Methods:
- In vitro and in vivo studies using flow cytometry, western blotting, xenografts, and time-lapse imaging.
- Protein interaction and ubiquitination analyses (GST pull-down, immunoprecipitation, mass spectrometry).
- Immunohistochemistry to assess LIV-1 expression in human cancers.
Main Results:
- LIV-1 overexpression induced apoptosis; LIV-1 depletion promoted mitotic exit from arrest.
- The LIV-1-GRPEL1 axis stabilizes GRPEL1 by preventing its ubiquitination.
- This axis modulates mitotic arrest via PP2A-B55α activity and inhibits apoptosis by interacting with AIF.
Conclusions:
- The LIV-1-GRPEL1 axis is a key regulator of both mitotic exit and apoptosis.
- Dysregulation of this axis is common in human epithelial cancers, suggesting its therapeutic relevance.
- This axis represents a novel mechanism for determining cell fate following mitotic damage.
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