Evidence map›Paper›PMID 23874207›Full record

ArticlePLoS genetics2013

NTRK3 is a potential tumor suppressor gene commonly inactivated by epigenetic mechanisms in colorectal cancer.

Yanxin Luo, Andrew M Kaz, Samornmas Kanngurn, Piri Welsch, Shelli M Morris, Jianping Wang, James D Lutterbaugh, Sanford D Markowitz, William M Grady

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02328677 (ColoCare Transdisciplinary Research in Colorectal Cancer Prognosis), which is not on this map. Cited by 70 papers.

0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed
2.8field-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.

NCT02328677 recruitingnot on this map

ColoCare Transdisciplinary Research in Colorectal Cancer Prognosis

TypeobservationalSponsorUniversity of UtahRan2007 to 2030Enrolled5,000ConditionsColorectal Cancer
3 · Its place in the literature

Who cites it

70 citing papers in PubMed, 109 citations in OpenAlex.

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  2. mAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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10 more citing papers are in PubMed but not listed here.

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

9 authors at 6 institutions in 3 countries.

Yanxin LuoDepartment of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, PR China.
Andrew M Kaz
Samornmas Kanngurn
Piri Welsch
Shelli M Morris
Jianping Wang
James D Lutterbaugh
Sanford D Markowitz
William M Grady
Fred Hutch Cancer Center · USCase Western Reserve University · USPrince of Songkla University · THSixth Affiliated Hospital of Sun Yat-sen University · CNSun Yat-sen University · CNUniversity of Washington Medical Center · US

Funding

Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Marian Esvelt · 1985 to 2026
$296.4M
Tumor mutation signaturesP01CA077852 · NCI · UNIVERSITY OF WASHINGTON · PI MONNAT, RAYMOND J · 1999 to 2019
$26.0M
Targeting 15-PGDH in Colon Cancer Prognosis, Prediction, Treatment and PreventionP50CA150964 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI MARKOWITZ, SANFORD D. · 2011 to 2022
$24.6M
Trans-NetworkU54CA143862 · NCI · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · PI MELDRUM, DEIRDRE R. · 2009 to 2013
$8.4M
Identify and validate novel epigenetic molecular markers for colorectal neoplasmU01CA152756 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI GRADY, WILLIAM MALLORY, GUDA, KISHORE · 2010 to 2021
$6.7M
TGF-beta signaling and colon cancerR01CA115513 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI GRADY, WILLIAM MALLORY · 2007 to 2011
$1.6M
NCI NIH HHS 5P50CA150964NCI NIH HHS P01 CA077852NCI NIH HHS P01CA077852NCI NIH HHS P30 CA015704NCI NIH HHS P30CA15704NCI NIH HHS P50 CA150964NCI NIH HHS R01 CA115513NCI NIH HHS R01CA115513NCI NIH HHS U01 CA152756NCI NIH HHS U54 CA143862NCI NIH HHS U54CA143862NCI NIH HHS UO1CA152756
6 · The paper itself

Abstract

NTRK3 is a member of the neurotrophin receptor family and regulates cell survival. It appears to be a dependence receptor, and thus has the potential to act as an oncogene or as a tumor suppressor gene. NTRK3 is a receptor for NT-3 and when bound to NT-3 it induces cell survival, but when NT-3 free, it induces apoptosis. We identified aberrantly methylated NTRK3 in colorectal cancers through a genome-wide screen for hypermethylated genes. This discovery led us to assess whether NTRK3 could be a tumor suppressor gene in the colon. NTRK3 is methylated in 60% of colon adenomas and 67% of colon adenocarcinomas. NTRK3 methylation suppresses NTRK3 expression. Reconstitution of NTRK3 induces apoptosis in colorectal cancers, if NT-3 is absent. Furthermore, the loss of NTRK3 expression associates with neoplastic transformation in vitro and in vivo. We also found that a naturally occurring mutant NTRK3 found in human colorectal cancer inhibits the tumor suppressor activity of NTRK3. In summary, our findings suggest NTRK3 is a conditional tumor suppressor gene that is commonly inactivated in colorectal cancer by both epigenetic and genetic mechanisms whose function in the pathogenesis of colorectal cancer depends on the expression status of its ligand, NT-3.

Indexed as

Genes, Tumor SuppressorAgedApoptosisColorectal NeoplasmsDNA MethylationEpigenetic RepressionFemaleGene Expression Regulation, NeoplasticGenome, HumanHCT116 CellsHumansMaleMiddle AgedNeoplasm StagingPolysaccharidesPromoter Regions, GeneticneurotropinPolysaccharidesReceptor, trkC

Identifiers

PMID23874207
PMCPMC3708790
OpenAlexW1988579734

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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.