Evidence map›Paper›PMID 26149735›Full record

ArticleThe pharmacogenomics journal2016

Genetic screening reveals a link between Wnt signaling and antitubulin drugs.

A H Khan, J S Bloom, E Faridmoayer, D J Smith

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

Article in The pharmacogenomics journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.3field-weighted citation impact, top 42% 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

4 citing papers in PubMed, 12 citations in OpenAlex.

  1. Review
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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

4 authors at 1 institution in 1 country.

A H KhanDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
J S BloomDepartment of Human Genetics, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
E FaridmoayerDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
D J SmithDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
University of California, Los Angeles · US

Funding

Deep RNA sequencing and proteomic analysis of a hybrid mouse diversity panelR01GM098273 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SMITH, DESMOND JAMES · 2012 to 2015
$1.6M
A cost-effective platform for high-precision genome analysis of mammalian cellsR21HG007405 · NHGRI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SMITH, DESMOND JAMES · 2015 to 2016
$424k
NHGRI NIH HHS R21 HG007405NIGMS NIH HHS R01 GM098273
6 · The paper itself

Abstract

The antitubulin drugs, paclitaxel (PX) and colchicine (COL), inhibit cell growth and are therapeutically valuable. PX stabilizes microtubules, while COL promotes their depolymerization. But, the drug concentrations that alter tubulin polymerization are hundreds of times higher than their clinically useful levels. To map genetic targets for drug action at single-gene resolution, we used a human radiation hybrid panel. We identified loci that affected cell survival in the presence of five compounds of medical relevance. For PX and COL, the zinc and ring finger 3 (ZNRF3) gene dominated the genetic landscape at therapeutic concentrations. ZNRF3 encodes an R-spondin regulated receptor that inhibits Wingless/Int (Wnt) signaling. Overexpression of the ZNRF3 gene shielded cells from antitubulin drug action, while small interfering RNA knockdowns resulted in sensitization. Further a potent pharmacological inhibitor of Wnt signaling, Wnt-C59, protected cells from PX and COL. Our results suggest that the antitubulin drugs perturb microtubule dynamics, thereby influencing Wnt signaling.

Indexed as

Quantitative Trait LociAnimalsAntineoplastic AgentsCell LineCell SurvivalColchicineCricetinaeHumansHybrid CellsPaclitaxelSignal TransductionTubulin ModulatorsUbiquitin-Protein LigasesWnt ProteinsAntineoplastic AgentsColchicinePaclitaxelTubulin ModulatorsUbiquitin-Protein LigasesWnt ProteinsZNRF3 protein, human

Identifiers

PMID26149735
PMCPMC4705004
OpenAlexW826213144

What OpenQuestion holds

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LicenceCC BY-NC-SA
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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.