Evidence map›Paper›PMID 31636012›Full record

ArticleEBioMedicine2019

The LIV-1-GRPEL1 axis adjusts cell fate during anti-mitotic agent-damaged mitosis.

Pingbo Chen, Beibei Wang, Qingqing Mo, Peng Wu, Yong Fang, Yuan Tian, Xin Jin, Yue Gao, Yuan Wu, Yang Cao and 8 more

Open access · goldAbstract read
In one paragraph

Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.2field-weighted citation impact, top 47% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 9 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 2 institutions in 1 country.

Pingbo ChenCancer 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.
Beibei WangCancer 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.
Qingqing MoCancer 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.
Peng WuCancer 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.
Yong FangCancer 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.
Yuan TianCancer 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.
Xin JinCancer 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.
Yue GaoCancer 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.
Yuan WuCancer 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.
Yang CaoDepartment of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Yang ZhangDepartment of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Ling XiCancer 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.
Shixuan WangCancer 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.
Junbo HuCancer 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.
Ding MaCancer 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.
Jianfeng ZhouCancer 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; Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Electronic address: jfzhou@tjh.tjmu.edu.cn.
Qinglei GaoCancer 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. Electronic address: qlgao@tjh.tjmu.edu.cn.
Gang ChenCancer 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. Electronic address: tjchengang@hust.edu.cn.
Tongji Hospital · CNHuazhong University of Science and Technology · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundUnderstanding 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.

methodsThe 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.

findingsOverexpression 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.

interpretationThese 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.

Indexed as

Cell LineageAnimalsAntimitotic AgentsApoptosisCation Transport ProteinsCell Cycle CheckpointsCell Line, TumorFemaleGene DeletionMaleMice, Inbred NODMice, SCIDMitosisMolecular ChaperonesNeoplasm ProteinsPaclitaxelAntimitotic AgentsCation Transport ProteinsGRPEL1 protein, humanGrpel1 protein, mouseMolecular ChaperonesNeoplasm ProteinsPaclitaxelSLC39A6 protein, humanSlc39a6 protein, mouseAnti-mitotic agentsApoptosisHuman cancerLIV-1-GRPEL1 axisMitotic exit

Identifiers

PMID31636012
PMCPMC6945280
OpenAlexW2981025188

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.