Evidence map›Paper›PMID 29396402›Full record

ArticleNature communications2018

Tuning microtubule dynamics to enhance cancer therapy by modulating FER-mediated CRMP2 phosphorylation.

Yiyan Zheng, Ritika Sethi, Lingegowda S Mangala, Charlotte Taylor, Juliet Goldsmith, Ming Wang, Kenta Masuda, Eli M Carrami, David Mannion, Fabrizio Miranda and 21 more

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2018. 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 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
4.2field-weighted citation impact, top 5% 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

27 citing papers in PubMed, 58 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

31 authors at 9 institutions in 5 countries.

Yiyan ZhengOvarian Cancer Cell Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford, OX3 9DS, UK.
Ritika SethiStructural Genomics Consortium, Nuffield Department of Medicine, University of Oxford, Old Road Campus Research Building, Oxford, OX3 7DQ, UK.
Lingegowda S MangalaDepartment of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA.
Charlotte TaylorOvarian Cancer Cell Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford, OX3 9DS, UK.
Juliet GoldsmithOvarian Cancer Cell Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford, OX3 9DS, UK.
Ming WangOvarian Cancer Cell Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford, OX3 9DS, UK.
Kenta MasudaOvarian Cancer Cell Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford, OX3 9DS, UK.
Eli M CarramiOvarian 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.
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.
Fiona ChenOvarian Cancer Cell Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford, OX3 9DS, UK.
Abdulkhaliq AlsaadiOvarian Cancer Cell Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford, OX3 9DS, UK.
Ashwag AlbukhariOvarian Cancer Cell Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford, OX3 9DS, UK.
Donatien Chedom FotsoOvarian Cancer Cell Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford, OX3 9DS, UK.
Christopher YauWellcome Trust Centre for Human Genetics and NIHR Biomedical Research Centre, Roosevelt Drive, Oxford, OX3 7BN, UK.
Dahai JiangDepartment of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA.
Sunila PradeepDepartment of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA.
Cristian Rodriguez-AguayoCenter for RNAi and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA.
Gabriel Lopez-BeresteinCenter for RNAi and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA.
Stefan KnappStructural Genomics Consortium, Nuffield Department of Medicine, University of Oxford, Old Road Campus Research Building, Oxford, OX3 7DQ, UK.
Nathanael S GrayDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, 02115, USA.ORCID 0000-0001-5354-7403
Leticia CampoDepartment of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK.
Kevin A MyersDepartment of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK.
Sunanda DharDepartment of Histopathology, Oxford University Hospitals, Oxford, OX3 9DU, UK.
David FergusonNuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine University of Oxford, Oxford University Hospitals, Oxford, OX3 9DU, UK.ORCID 0000-0001-5045-819X
Robert C BastDepartment of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Anil K SoodDepartment of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA.
Frank von DelftStructural Genomics Consortium, Nuffield Department of Medicine, University of Oxford, Old Road Campus Research Building, Oxford, OX3 7DQ, UK.ORCID 0000-0003-0378-0017
Ahmed Ashour AhmedOvarian Cancer Cell Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford, OX3 9DS, UK. ahmed.ahmed@obs-gyn.ox.ac.uk.
John Radcliffe Hospital · GBThe University of Texas MD Anderson Cancer Center · USUniversity of Oxford · GBCentre for Human Genetics · GBGoethe University Frankfurt · DEHarvard University · USKing Abdulaziz University · SAOxford University Hospitals NHS Trust · GBUniversity of Johannesburg · ZA

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

Though used widely in cancer therapy, paclitaxel only elicits a response in a fraction of patients. A strong determinant of paclitaxel tumor response is the state of microtubule dynamic instability. However, whether the manipulation of this physiological process can be controlled to enhance paclitaxel response has not been tested. Here, we show a previously unrecognized role of the microtubule-associated protein CRMP2 in inducing microtubule bundling through its carboxy terminus. This activity is significantly decreased when the FER tyrosine kinase phosphorylates CRMP2 at Y479 and Y499. The crystal structures of wild-type CRMP2 and CRMP2-Y479E reveal how mimicking phosphorylation prevents tetramerization of CRMP2. Depletion of FER or reducing its catalytic activity using sub-therapeutic doses of inhibitors increases paclitaxel-induced microtubule stability and cytotoxicity in ovarian cancer cells and in vivo. This work provides a rationale for inhibiting FER-mediated CRMP2 phosphorylation to enhance paclitaxel on-target activity for cancer therapy.

Indexed as

RNAi TherapeuticsAnimalsCell Line, TumorFemaleHumansIntercellular Signaling Peptides and ProteinsMiceMice, NudeMicroscopy, ConfocalMicroscopy, FluorescenceMicrotubulesMolecular Dynamics SimulationMolecular Targeted TherapyNeoplasm TransplantationNerve Tissue ProteinsOvarian Neoplasmscollapsin response mediator protein-2Intercellular Signaling Peptides and ProteinsNerve Tissue ProteinsPaclitaxelProtein-Tyrosine Kinasesproto-oncogene protein c-fes-fpsRNA, Small InterferingTubulin Modulators

Identifiers

PMID29396402
PMCPMC5797184
OpenAlexW2793714035

What Socratic 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 Socratic graph.