Evidence map›Paper›PMID 21514161›Full record

ArticleCurrent biology : CB2011

Amphiregulin exosomes increase cancer cell invasion.

James N Higginbotham, Michelle Demory Beckler, Jonathan D Gephart, Jeffrey L Franklin, Galina Bogatcheva, Gert-Jan Kremers, David W Piston, Gregory D Ayers, Russell E McConnell, Matthew J Tyska and 1 more

Open access · bronzeAbstract readComparative Study
In one paragraph

Article in Current biology : CB, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 200 papers.

0numbers the graph read from it
0cells of the map it votes in
200citing papers in PubMed
9.6field-weighted citation impact, top 1% 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

200 citing papers in PubMed, 356 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. Review
  5. Article
  6. Niche-derived exosomes controlFrontiers in immunology · 2026
    Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Amphiregulin in Fibrotic Diseases and Cancer.International journal of molecular sciences · 2025
    Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. [Therapeutic mechanism of aqueous extract ofNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024
    Article
  20. Article

140 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

11 authors at 1 institution in 1 country.

James N HigginbothamDepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Michelle Demory Beckler
Jonathan D Gephart
Jeffrey L Franklin
Galina Bogatcheva
Gert-Jan Kremers
David W Piston
Gregory D Ayers
Russell E McConnell
Matthew J Tyska
Robert J Coffey
Vanderbilt University Medical Center · US

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Jin Chen · 1995 to 2026
$172.8M
Understanding and Controlling p120 Dysfunction in CRCP50CA095103 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI COFFEY, ROBERT J. · 2002 to 2017
$33.6M
Translational Analysis CoreP30DK058404 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 2002 to 2026
$29.9M
TRANSFORMING GROWTH FACTORS IN COLONIC NEOPLASIAR01CA046413 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI COFFEY, ROBERT J. · 1988 to 2016
$8.8M
BIOCHEMICAL &CHEMICAL TRAINING FOR CANCER RESEARCHT32CA009582 · NCI · VANDERBILT UNIVERSITY · PI David K Cortez · 1987 to 2026
$8.8M
Multidisciplinary Training in Basic and Translational Imaging of CancerR25CA092043 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MANNING, HENRY CHARLES · 2001 to 2015
$6.6M
Training Program in Stem Cell and Regenerative Developmental BiologyT32HD007502 · NICHD · VANDERBILT UNIVERSITY · PI WRIGHT, CHRISTOPHER V · 1997 to 2022
$5.4M
Regulation of Brush Border Structure by Myosin-1aR01DK075555 · NIDDK · VANDERBILT UNIVERSITY · PI TYSKA, MATTHEW J · 2007 to 2016
$2.7M
Probes:Quantitative Optical and Electron Microscopy(RMI)P20GM072048 · NIGMS · VANDERBILT UNIVERSITY · PI PISTON, DAVID W. · 2004 to 2007
$2.7M
Role of EGFR ligand-containing exosomes in colorectal cancerR01CA163563 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI COFFEY, ROBERT J. · 2013 to 2016
$1.7M
NCI NIH HHS 1R25 CA92043NCI NIH HHS CA46413NCI NIH HHS P30 CA068485NCI NIH HHS P30 CA68485NCI NIH HHS P50 CA095103NCI NIH HHS R01 CA046413NCI NIH HHS R01 CA163563NCI NIH HHS R25 CA092043NCI NIH HHS T32 CA009582NICHD NIH HHS T32 HD007502NIDDK NIH HHS DK058404NIDDK NIH HHS DK075555NIDDK NIH HHS P30 DK058404NIDDK NIH HHS R01 DK075555NIGMS NIH HHS GM72048NIGMS NIH HHS P20 GM072048PHS HHS P50 95103
6 · The paper itself

Abstract

Autocrine, paracrine, and juxtacrine are recognized modes of action for mammalian EGFR ligands including EGF, TGF-α (TGFα), amphiregulin (AREG), heparin-binding EGF-like growth factor (HB-EGF), betacellulin, epiregulin, and epigen. We identify a new mode of EGFR ligand signaling via exosomes. Human breast and colorectal cancer cells release exosomes containing full-length, signaling-competent EGFR ligands. Exosomes isolated from MDCK cells expressing individual full-length EGFR ligands displayed differential activities; AREG exosomes increased invasiveness of recipient breast cancer cells 4-fold over TGFα or HB-EGF exosomes and 5-fold over equivalent amounts of recombinant AREG. Exosomal AREG displayed significantly greater membrane stability than TGFα or HB-EGF. An average of 24 AREG molecules are packaged within an individual exosome, and AREG exosomes are rapidly internalized by recipient cells. Whether the composition and behavior of exosomes differ between nontransformed and transformed cells is unknown. Exosomes from DLD-1 colon cancer cells with a mutant KRAS allele exhibited both higher AREG levels and greater invasive potential than exosomes from isogenically matched, nontransformed cells in which mutant KRAS was eliminated by homologous recombination. We speculate that EGFR ligand signaling via exosomes might contribute to diverse cancer phenomena such as field effect and priming of the metastatic niche.

Indexed as

AmphiregulinAnimalsCell Line, TumorCentrifugationDogsEGF Family of ProteinsElectrophoresis, Polyacrylamide GelEnzyme-Linked Immunosorbent AssayErbB ReceptorsExosomesGlycoproteinsHeparin-binding EGF-like Growth FactorHumansImmunoblottingIntercellular Signaling Peptides and ProteinsMicroscopy, ElectronAmphiregulinAREG protein, humanEGF Family of ProteinsErbB ReceptorsGlycoproteinsHBEGF protein, humanHeparin-binding EGF-like Growth FactorIntercellular Signaling Peptides and ProteinsTransforming Growth Factor alpha

Identifiers

PMID21514161
PMCPMC3417320
OpenAlexW2063508984

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.