Evidence map›Paper›PMID 26133385›Full record

ArticleMolecular biology of the cell2015

Cell-based screen for altered nuclear phenotypes reveals senescence progression in polyploid cells after Aurora kinase B inhibition.

Mahito Sadaie, Christian Dillon, Masako Narita, Masashi Narita, Andrew R J Young, Claire J Cairney, Lauren S Godwin, Christopher J Torrance, Dorothy C Bennett, W Nicol Keith and 1 more

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in Molecular biology of the cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 36 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 1 pooled it
3.1field-weighted citation impact, top 9% 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

36 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.

  1. Pooled it
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  5. Review
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  8. Review
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  10. Studying Hepatic Stellate Cell Senescence.Methods in molecular biology (Clifton, N.J.) · 2023
    Review
  11. Article
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  16. Harnessing α-l-fucosidase forChemical science · 2021
    Article
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4 · The record

Corrections and comments

  • Erratum issued
    Correction.2015 · Narita, Masashi [Corrected to Narita, Masako]
5 · Who and what money

Authors and funding

11 authors at 4 institutions in 1 country.

Mahito SadaieCancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, United Kingdom.
Christian DillonCancer Research Technology Discovery Laboratories, Wolfson Institute for Biomedical Research, London WC1E 6BT, United Kingdom.
Masako Narita
Masashi NaritaCancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, United Kingdom Masashi.Narita@cruk.cam.ac.uk.
Andrew R J YoungCancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, United Kingdom.
Claire J CairneyInstitute of Cancer Sciences, Wolfson Wohl Cancer Research Centre, University of Glasgow, Glasgow G61 1QH, United Kingdom.
Lauren S GodwinSt. George's, University of London, London SW17 0RE, United Kingdom.
Christopher J TorranceHorizon Discovery Ltd, IQ Cambridge, Waterbeach, Cambridge CB25 9TL, United Kingdom.
Dorothy C BennettSt. George's, University of London, London SW17 0RE, United Kingdom.
W Nicol KeithInstitute of Cancer Sciences, Wolfson Wohl Cancer Research Centre, University of Glasgow, Glasgow G61 1QH, United Kingdom.
Masashi NaritaCancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, United Kingdom.
University of Cambridge · GBSt George's, University of London · GBUniversity of Glasgow · GBHorizon Discovery (United Kingdom) · GB

Funding

Cancer Research UK 15890Cancer Research UK A6691Cancer Research UK A9892
6 · The paper itself

Abstract

Cellular senescence is a widespread stress response and is widely considered to be an alternative cancer therapeutic goal. Unlike apoptosis, senescence is composed of a diverse set of subphenotypes, depending on which of its associated effector programs are engaged. Here we establish a simple and sensitive cell-based prosenescence screen with detailed validation assays. We characterize the screen using a focused tool compound kinase inhibitor library. We identify a series of compounds that induce different types of senescence, including a unique phenotype associated with irregularly shaped nuclei and the progressive accumulation of G1 tetraploidy in human diploid fibroblasts. Downstream analyses show that all of the compounds that induce tetraploid senescence inhibit Aurora kinase B (AURKB). AURKB is the catalytic component of the chromosome passenger complex, which is involved in correct chromosome alignment and segregation, the spindle assembly checkpoint, and cytokinesis. Although aberrant mitosis and senescence have been linked, a specific characterization of AURKB in the context of senescence is still required. This proof-of-principle study suggests that our protocol is capable of amplifying tetraploid senescence, which can be observed in only a small population of oncogenic RAS-induced senescence, and provides additional justification for AURKB as a cancer therapeutic target.

Indexed as

PolyploidyAurora Kinase BCell DivisionCell LineCell NucleusCellular SenescenceChromosome SegregationCytokinesisHeLa CellsHigh-Throughput Screening AssaysHumansMitosisPhenotypeProtein Kinase InhibitorsSmall Molecule LibrariesAurora Kinase BProtein Kinase InhibitorsSmall Molecule Libraries

Identifiers

PMID26133385
PMCPMC4551313
OpenAlexW2100695898

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

None linked

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.