Evidence map›Paper›PMID 15668738›Full record

ArticleThe Journal of clinical investigation2005

Transcriptional activation of integrin beta6 during the epithelial-mesenchymal transition defines a novel prognostic indicator of aggressive colon carcinoma.

Richard C Bates, David I Bellovin, Courtney Brown, Elizabeth Maynard, Bingyan Wu, Hisaaki Kawakatsu, Dean Sheppard, Peter Oettgen, Arthur M Mercurio

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 184 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
184citing papers in PubMed, 1 pooled it
7.6field-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

184 citing papers in PubMed, 1 synthesis or guideline pooled it, 328 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Comparison of theMolecular therapy. Oncology · 2026
    Article
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  5. Synthesis and preclinical development of a novelEJNMMI radiopharmacy and chemistry · 2026
    Article
  6. Review
  7. Anoikis: To Die or Not to Die?International journal of molecular sciences · 2026
    Review
  8. Article
  9. Article
  10. Integrin αvβ6-Targeted PET/CT Imaging of Non-Small Cell Lung Cancer with [Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Observational
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. European journal of nuclear medicine and molecular imaging · 2024
    Article
  18. TGFβ in Pancreas and Colorectal Cancer: Opportunities to Overcome Therapeutic Resistance.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
    Review
  19. Review
  20. Article

124 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 4 institutions in 1 country.

Richard C BatesDivision of Cancer Biology and Angiogenesis, Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA. rbates@caregroup.harvard.edu
David I Bellovin
Courtney Brown
Elizabeth Maynard
Bingyan Wu
Hisaaki Kawakatsu
Dean Sheppard
Peter Oettgen
Arthur M Mercurio
Beth Israel Deaconess Medical Center · USAngiogenesis Foundation · USUniversity of California, San Francisco · USDana-Farber Cancer Institute · US

Funding

STRUCTURE-FUNCTION RELATIONSHIPS IN THE ALIMENTARY TRACTP30DK034854 · NIDDK · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI JONATHAN C KAGAN · 1986 to 2026
$32.4M
INTEGRIN FUNCTION AND SIGNALING IN CARCINOMA PROGRESSIONR01CA080789 · NCI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI MERCURIO, ARTHUR M · 1999 to 2012
$4.7M
Epithelial Mesenchymal Transition and Invasive CarcinomaR01CA107548 · NCI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI MERCURIO, ARTHUR M · 2004 to 2008
$1.5M
NCI NIH HHS CA107548NCI NIH HHS CA 80789NCI NIH HHS R01 CA080789NCI NIH HHS R01 CA107548NIDDK NIH HHS DK34854NIDDK NIH HHS P30 DK034854
6 · The paper itself

Abstract

We used a spheroid model of colon carcinoma to analyze integrin dynamics as a function of the epithelial-mesenchymal transition (EMT), a process that provides a paradigm for understanding how carcinoma cells acquire a more aggressive phenotype. This EMT involves transcriptional activation of the beta6 integrin subunit and a consequent induction of alphavbeta6 expression. This integrin enhances the tumorigenic properties of colon carcinoma, including activation of autocrine TGF-beta and migration on interstitial fibronectin. Importantly, this study validates the clinical relevance of the EMT. Kaplan-Meier analysis of beta6 expression in 488 colorectal carcinomas revealed a striking reduction in median survival time of patients with high beta6 expression. Elevated receptor expression did not simply reflect increasing tumor stage, since log-rank analysis showed a more significant impact on the survival of patients with early-stage, as opposed to late-stage, disease. Cox regression analysis confirmed that this integrin is an independent variable for these tumors. These findings define the alphavbeta6 integrin as an important risk factor for early-stage disease and a novel therapeutic candidate for colorectal cancer.

Indexed as

AnimalsAutocrine CommunicationBiomarkers, TumorCarcinomaColonic NeoplasmsFemaleGene Expression Regulation, NeoplasticHumansIntegrin alpha5Integrin beta ChainsIntestinal MucosaMesodermMiceMice, NudeNeoplasm InvasivenessPrognosisBiomarkers, TumorIntegrin alpha5integrin beta6Integrin beta ChainsTransforming Growth Factor beta

Identifiers

PMID15668738
PMCPMC544606
OpenAlexW2153284298

What Socratic holds

Textmetadata
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 Socratic graph.