Evidence map›Paper›PMID 22891766›Full record

ArticleBMC biology2012

TWIST1 associates with NF-κB subunit RELA via carboxyl-terminal WR domain to promote cell autonomous invasion through IL8 production.

Shan Li, Stephen E Kendall, Raquel Raices, James Finlay, Maricela Covarrubias, Zheng Liu, Gina Lowe, Yu-Huey Lin, Yuan Han Teh, Victoria Leigh and 4 more

Open access · goldAbstract read
In one paragraph

Article in BMC biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

43 citing papers in PubMed, 58 citations in OpenAlex.

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  9. Article
  10. Prognostic Value of TWIST1 and EZH2 Expression in Colon Cancer.Journal of gastrointestinal cancer · 2021
    Article
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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

14 authors at 6 institutions in 2 countries.

Shan LiDivision of Neurosciences, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.
Stephen E Kendall
Raquel Raices
James Finlay
Maricela Covarrubias
Zheng Liu
Gina Lowe
Yu-Huey Lin
Yuan Han Teh
Victoria Leigh
Simi Dhillon
Steven Flanagan
Karen S Aboody
Carlotta A Glackin
Beckman Research InstituteCity of Hope · USAffymax (United States) · USGeneTex (United States) · USPomona College · USWestern University of Health Sciences · US

Funding

Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI STANLEY R. HAMILTON · 1985 to 2026
$86.3M
Molecular Interactions of TWIST and Wnt in Breast CancerR21CA107245 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI GLACKIN, CARLOTTA A · 2005 to 2006
$287k
NCI NIH HHS P30 CA033572NCI NIH HHS R21 CA107245
6 · The paper itself

Abstract

backgroundMetastasis is the primary cause of death for cancer patients. TWIST1, an evolutionarily conserved basic helix-loop-helix (bHLH) transcription factor, is a strong promoter of metastatic spread and its expression is elevated in many advanced human carcinomas. However, the molecular events triggered by TWIST1 to motivate dissemination of cancer cells are largely unknown.

resultsHere we show that TWIST1 induces the production of interleukin 8 (IL8), which activates matrix metalloproteinases and promotes invasion of breast epithelial and cancer cells. In this novel mechanism, TWIST1-mediated IL8 transcription is induced through the TWIST1 carboxy-terminal WR (Trp-Arg) domain instead of the classic DNA binding bHLH domain. Co-immunoprecipitation analyses revealed that the WR domain mediates the formation of a protein complex comprised of TWIST1 and the nuclear factor-kappaB (NF-κB) subunit RELA (p65/NF-κB3), which synergistically activates the transcriptional activity of NF-κB. This activation leads to increased DNA binding affinity of RELA to the IL8 promoter and thus induces the expression of the cytokine. Blockage of IL8 signaling by IL8 neutralizing antibodies or receptor inhibition reduced the invasiveness of both breast epithelial and cancer cells, indicating that TWIST1 induces autonomous cell invasion by establishing an IL8 antocrine loop.

conclusionsOur data demonstrate that the TWIST1 WR domain plays a critical role in TWIST1-induced IL8 expression through interactions with and activation of NF-κB. The produced IL8 signals through an autocrine loop and promotes extracellular matrix degradation to enable cell invasion across the basement membrane.

Indexed as

Breast NeoplasmsCell Line, TumorFemaleHumansInterleukin-8Neoplasm InvasivenessNF-kappa BNuclear ProteinsPromoter Regions, GeneticProtein Structure, TertiaryTranscription Factor RelATwist-Related Protein 1CXCL8 protein, humanInterleukin-8NF-kappa BNuclear ProteinsRELA protein, humanTranscription Factor RelATWIST1 protein, humanTwist-Related Protein 1

Identifiers

PMID22891766
PMCPMC3482588
OpenAlexW1979050814

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.