Evidence map›Paper›PMID 28738084›Full record

ArticlePloS one2017

The Dkk3 gene encodes a vital intracellular regulator of cell proliferation.

Jack L Leonard, Deborah M Leonard, Scot A Wolfe, Jilin Liu, Jaime Rivera, Michelle Yang, Ryan T Leonard, Jacob P S Johnson, Prashant Kumar, Kate L Liebmann and 3 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in PloS one, 2017. 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 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
1.6field-weighted citation impact, top 17% 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

18 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.

  1. Pooled it
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  14. Dickkopf Homolog 3Frontiers in oncology · 2019
    Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 1 institution in 1 country.

Jack L LeonardDepartment of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.ORCID http://orcid.org/0000-0003-2210-6781
Deborah M LeonardProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
Scot A WolfeDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
Jilin LiuDepartment of Cell and Molecular Physiology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
Jaime RiveraDepartment of Cell and Developmental Biology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
Michelle YangDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
Ryan T LeonardDepartment of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
Jacob P S JohnsonDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
Prashant KumarDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
Kate L LiebmannDepartment of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
Amanda A TuttoDepartment of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
Zhongming MouDepartment of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
Karl J SiminDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
University of Massachusetts Chan Medical School · US

Funding

TH-Dependent, Actin-Based Vesicle TraffickingR01DK060051 · NIDDK · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LEONARD, JACK L. · 2001 to 2005
$1.7M
MECHANISMS OF STEROID RECEPTOR ACTIVATIONZ01DK060051 · NIDDK · DIABETES, DIGESTIVE, KIDNEY DISEASES · PI BARSONY, JULIANNA · 1998 to 2006
–
Intramural NIH HHS Z01 DK060051NIDDK NIH HHS R01 DK060051
6 · The paper itself

Abstract

Members of the Dickkopf (Dkk) family of Wnt antagonists interrupt Wnt-induced receptor assembly and participate in axial patterning and cell fate determination. One family member, DKK3, does not block Wnt receptor activation. Loss of Dkk3 expression in cancer is associated with hyperproliferation and dysregulated ß-catenin signaling, and ectopic expression of Dkk3 halts cancer growth. The molecular events mediating the DKK3-dependent arrest of ß-catenin-driven cell proliferation in cancer cells are unknown. Here we report the identification of a new intracellular gene product originating from the Dkk3 locus. This Dkk3b transcript originates from a second transcriptional start site located in intron 2 of the Dkk3 gene. It is essential for early mouse development and is a newly recognized regulator of ß-catenin signaling and cell proliferation. Dkk3b interrupts nuclear translocation ß-catenin by capturing cytoplasmic, unphosphorylated ß-catenin in an extra-nuclear complex with ß-TrCP. These data reveal a new regulator of one of the most studied signal transduction pathways in metazoans and provides a novel, completely untapped therapeutic target for silencing the aberrant ß-catenin signaling that drives hyperproliferation in many cancers.

Indexed as

Animalsbeta Cateninbeta-Transducin Repeat-Containing ProteinsCell ProliferationCytoplasmFemaleIntercellular Signaling Peptides and ProteinsMice, Inbred C57BLNeoplasmsPregnancyRatsRats, Sprague-DawleySignal TransductionWnt Proteinsbeta Cateninbeta-Transducin Repeat-Containing ProteinsIntercellular Signaling Peptides and ProteinsWnt Proteins

Identifiers

PMID28738084
PMCPMC5524345
OpenAlexW2739460727

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.