Evidence map›Paper›PMID 26363006›Full record

ArticleCancer research2015

A TDO2-AhR signaling axis facilitates anoikis resistance and metastasis in triple-negative breast cancer.

Nicholas C D'Amato, Thomas J Rogers, Michael A Gordon, Lisa I Greene, Dawn R Cochrane, Nicole S Spoelstra, Travis G Nemkov, Angelo D'Alessandro, Kirk C Hansen, Jennifer K Richer

Abstract read
In one paragraph

Article in Cancer research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 197 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
197citing papers in PubMed, 2 pooled it
5.3field-weighted citation impact, top 3% 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

197 citing papers in PubMed, 2 syntheses or guidelines pooled it, 296 citations in OpenAlex.

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  12. Association of IL4I1Frontiers in immunology · 2026
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137 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

10 authors at 1 institution in 1 country.

Nicholas C D'AmatoDepartment of Pathology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Thomas J RogersDepartment of Pathology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Michael A GordonDepartment of Pathology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Lisa I GreeneDepartment of Pathology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Dawn R CochraneDepartment of Pathology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Nicole S SpoelstraDepartment of Pathology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Travis G NemkovDepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Angelo D'AlessandroDepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Kirk C HansenDepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Jennifer K RicherDepartment of Pathology, University of Colorado Anschutz Medical Campus, Aurora, Colorado. Jennifer.Richer@ucdenver.edu.
University of Colorado Anschutz Medical Campus · US

Funding

University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
NCI NIH HHS P30 CA046934NCI NIH HHS P30CA046934
6 · The paper itself

Abstract

The ability of a cancer cell to develop resistance to anoikis, a programmed cell death process triggered by substratum detachment, is a critical step in the metastatic cascade. Triple-negative breast cancers (TNBC) exhibit higher rates of metastasis after diagnosis, relative to estrogen-positive breast cancers, but while TNBC cells are relatively more resistant to anoikis, the mechanisms involved are unclear. Through gene expression and metabolomic profiling of TNBC cells in forced suspension culture, we identified a molecular pathway critical for anchorage-independent cell survival. TNBC cells in suspension upregulated multiple genes in the kynurenine pathway of tryptophan catabolism, including the enzyme tryptophan 2,3-dioxygenase (TDO2), in an NF-κB-dependent manner. Kynurenine production mediated by TDO2 in TNBC cells was sufficient to activate aryl hydrocarbon receptor (AhR), an endogenous kynurenine receptor. Notably, pharmacologic inhibition or genetic attenuation of TDO2 or AhR increased cellular sensitivity to anoikis, and also reduced proliferation, migration, and invasion of TNBC cells. In vivo, TDO2 inhibitor-treated TNBC cells inhibited colonization of the lung, suggesting that TDO2 enhanced metastatic capacity. In clinical specimens of TNBC, elevated expression of TDO2 was associated with increased disease grade, estrogen receptor-negative status, and shorter overall survival. Our results define an NF-κB-regulated signaling axis that promotes anoikis resistance, suggest functional connections with inflammatory modulation by the kynurenine pathway, and highlight TDO2 as an attractive target for treatment of this aggressive breast cancer subtype.

Indexed as

AnimalsAnoikisCell Line, TumorCell MovementCell ProliferationGene Expression Regulation, NeoplasticHumansKynurenineMiceMice, Inbred NODMice, SCIDNeoplasm InvasivenessNeoplasm MetastasisNF-kappa BReceptors, Aryl HydrocarbonRNA InterferenceKynurenineNF-kappa BReceptors, Aryl HydrocarbonRNA, Small InterferingTryptophan Oxygenase

Identifiers

PMID26363006
PMCPMC4631670
OpenAlexW1902958101

What OpenQuestion holds

Textmetadata
LicenceTDM
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.