Evidence map›Paper›PMID 28152500›Full record

ArticleOncotarget2017

Loss of PFKFB4 induces cell death in mitotically arrested ovarian cancer cells.

Charlotte Taylor, David Mannion, Fabrizio Miranda, Mohammad Karaminejadranjbar, Sandra Herrero-Gonzalez, Karin Hellner, Yiyan Zheng, Geoffrey Bartholomeusz, Robert C Bast, Ahmed Ashour Ahmed

Open access · diamondAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.3field-weighted citation impact, top 22% 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

14 citing papers in PubMed, 27 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

10 authors at 4 institutions in 2 countries.

Charlotte TaylorOvarian Cancer Cell Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford, OX3 9DS, UK.
David MannionOvarian Cancer Cell Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford, OX3 9DS, UK.
Fabrizio MirandaOvarian Cancer Cell Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford, OX3 9DS, UK.
Mohammad KaraminejadranjbarOvarian Cancer Cell Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford, OX3 9DS, UK.
Sandra Herrero-GonzalezOvarian Cancer Cell Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford, OX3 9DS, UK.
Karin HellnerOvarian Cancer Cell Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford, OX3 9DS, UK.
Yiyan ZhengOvarian Cancer Cell Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford, OX3 9DS, UK.
Geoffrey BartholomeuszDepartment of Experimental Therapeutics, M.D. Anderson Cancer Center, University of Texas, Houston, TX 77030, USA.
Robert C BastDepartment of Experimental Therapeutics, M.D. Anderson Cancer Center, University of Texas, Houston, TX 77030, USA.
Ahmed Ashour AhmedOvarian Cancer Cell Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford, OX3 9DS, UK.
John Radcliffe Hospital · GBMRC Weatherall Institute of Molecular Medicine · GBThe University of Texas MD Anderson Cancer Center · USUniversity of Oxford · GB

Funding

U.T. M. D. Anderson Cancer Center SPORE in Ovarian CancerP50CA217685 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI SOOD, ANIL K · 2017 to 2021
$7.9M
Medical Research Council G0902418NCI NIH HHS P50 CA217685
6 · The paper itself

Abstract

Taxanes represent some of the most commonly used chemotherapeutic agents for ovarian cancer treatment. However, they are only effective in approximately 40% of patients. Novel therapeutic strategies are required to potentiate their effect and improve patient outcome. A hallmark of many cancers is the constitutive activation of the PI3K/AKT pathway, which drives cell survival and metabolism. We discovered a striking decrease in AKT activity coupled with a significant reduction in glucose 6-phosphate and ATP levels during mitotic arrest in the majority of ovarian cancer cell lines tested, indicating a potential metabolic vulnerability. A high-content siRNA screen to detect novel metabolic targets in mitotically arrested ovarian cancer cells identified the glycolytic enzyme PFKFB4. PFKFB4 depletion increased caspase 3/7 activity, and levels of reactive oxygen species only in mitotically arrested cells, and significantly enhanced mitotic cell death after paclitaxel treatment. Depletion of PFKFB3 demonstrated a similar phenotype. The observation that some ovarian cancer cells lose AKT activity during mitotic arrest and become vulnerable to metabolic targeting is a new concept in cancer therapy. Thus, combining mitotic-targeted therapies with glycolytic inhibitors may act to potentiate the effects of antimitotics in ovarian cancer through mitosis-specific cell death.

Indexed as

Antineoplastic AgentsBlotting, WesternCell Cycle CheckpointsCell DeathCell Line, TumorFemaleFlow CytometryFluorescent Antibody TechniqueGene Knockdown TechniquesHumansMutagenesis, Site-DirectedOvarian NeoplasmsPaclitaxelPhosphofructokinase-2Polymerase Chain ReactionProto-Oncogene Proteins c-aktAntineoplastic AgentsPaclitaxelPFKFB3 protein, humanPFKFB4 protein, humanPhosphofructokinase-2Proto-Oncogene Proteins c-aktmitotic arrestovarian cancerpaclitaxelPFKFB3PFKFB4

Identifiers

PMID28152500
PMCPMC5392300
OpenAlexW2585911714

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.