Evidence map›Paper›PMID 25171411›Full record

ArticleCell2014

Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis.

Nicola Aceto, Aditya Bardia, David T Miyamoto, Maria C Donaldson, Ben S Wittner, Joel A Spencer, Min Yu, Adam Pely, Amanda Engstrom, Huili Zhu and 10 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1,464 papers.

0numbers the graph read from it
0cells of the map it votes in
1,464citing papers in PubMed
74.4field-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

1,464 citing papers in PubMed, 2,441 citations in OpenAlex.

  1. Trial
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  9. Cell plasticity in cancer and therapy resistance.Experimental & molecular medicine · 2026
    Review
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  13. Liquid biopsy in bladder cancer: towards precision oncology.Journal of translational medicine · 2026
    Review
  14. Article
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  16. Article
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1,404 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 3 institutions in 1 country.

Nicola AcetoMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02129, USA; Department of Medicine, Harvard Medical School, Boston, MA 02129, USA.
Aditya BardiaMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02129, USA; Department of Medicine, Harvard Medical School, Boston, MA 02129, USA.
David T MiyamotoMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02129, USA; Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.
Maria C DonaldsonMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02129, USA; Department of Medicine, Harvard Medical School, Boston, MA 02129, USA.
Ben S WittnerMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02129, USA; Department of Medicine, Harvard Medical School, Boston, MA 02129, USA.
Joel A SpencerAdvanced Microscopy Program, Wellman Center for Photomedicine and Center for Systems Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Stem Cell Institute, 1350 Massachusetts Avenue, Cambridge, MA 02138, USA.
Min YuMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02129, USA; Department of Medicine, Harvard Medical School, Boston, MA 02129, USA.
Adam PelyAdvanced Microscopy Program, Wellman Center for Photomedicine and Center for Systems Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Stem Cell Institute, 1350 Massachusetts Avenue, Cambridge, MA 02138, USA.
Amanda EngstromMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02129, USA; Department of Medicine, Harvard Medical School, Boston, MA 02129, USA.
Huili ZhuMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02129, USA; Department of Medicine, Harvard Medical School, Boston, MA 02129, USA.
Brian W BranniganMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02129, USA; Department of Medicine, Harvard Medical School, Boston, MA 02129, USA.
Ravi KapurCenter for Bioengineering in Medicine, Harvard Medical School, Boston, MA 02129, USA.
Shannon L StottMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02129, USA; Department of Medicine, Harvard Medical School, Boston, MA 02129, USA; Center for Bioengineering in Medicine, Harvard Medical School, Boston, MA 02129, USA.
Toshi ShiodaMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02129, USA; Department of Medicine, Harvard Medical School, Boston, MA 02129, USA.
Sridhar RamaswamyMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02129, USA; Department of Medicine, Harvard Medical School, Boston, MA 02129, USA.
David T TingMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02129, USA; Department of Medicine, Harvard Medical School, Boston, MA 02129, USA.
Charles P LinAdvanced Microscopy Program, Wellman Center for Photomedicine and Center for Systems Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Stem Cell Institute, 1350 Massachusetts Avenue, Cambridge, MA 02138, USA.
Mehmet TonerCenter for Bioengineering in Medicine, Harvard Medical School, Boston, MA 02129, USA; Department of Surgery, Harvard Medical School, Boston, MA 02129, USA.
Daniel A HaberMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02129, USA; Department of Medicine, Harvard Medical School, Boston, MA 02129, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: dhaber@mgh.harvard.edu.
Shyamala MaheswaranMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02129, USA; Department of Surgery, Harvard Medical School, Boston, MA 02129, USA. Electronic address: maheswaran@helix.mgh.harvard.edu.
Harvard University · USMassachusetts General Hospital · USHoward Hughes Medical Institute · US

Funding

StatisticsP50CA086355 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI WEISSLEDER, MD, PHD, RALPH · 2000 to 2015
$27.8M
Point-of care Microfluidics for Early Detection of CancerU01EB012493 · NIBIB · MASSACHUSETTS GENERAL HOSPITAL · PI HABER, DANIEL A., TONER, MEHMET · 2010 to 2018
$19.6M
Dana Farber/Harvard Cancer Consortium Career Development Program in Clinical OncologyK12CA087723 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI David Tsai Ting · 2002 to 2026
$17.9M
Modeling Metastasis and Acquired Drug Resistance Using Circulating Tumor CellsR01CA129933 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Daniel A. Haber · 2008 to 2026
$7.5M
Point-of-Care Microfluidics in Lung CancerR01EB008047 · NIBIB · MASSACHUSETTS GENERAL HOSPITAL · PI TONER, MEHMET · 2007 to 2009
$3.4M
Howard Hughes Medical InstituteNCI NIH HHS K12 CA087723NCI NIH HHS P50 CA086355NCI NIH HHS P50 CA086355-12NCI NIH HHS R01 CA129933NIBIB NIH HHS EB008047NIBIB NIH HHS R01 EB008047NIBIB NIH HHS U01 EB012493PHS HHS P41 E8015903-02S1
6 · The paper itself

Abstract

Circulating tumor cell clusters (CTC clusters) are present in the blood of patients with cancer but their contribution to metastasis is not well defined. Using mouse models with tagged mammary tumors, we demonstrate that CTC clusters arise from oligoclonal tumor cell groupings and not from intravascular aggregation events. Although rare in the circulation compared with single CTCs, CTC clusters have 23- to 50-fold increased metastatic potential. In patients with breast cancer, single-cell resolution RNA sequencing of CTC clusters and single CTCs, matched within individual blood samples, identifies the cell junction component plakoglobin as highly differentially expressed. In mouse models, knockdown of plakoglobin abrogates CTC cluster formation and suppresses lung metastases. In breast cancer patients, both abundance of CTC clusters and high tumor plakoglobin levels denote adverse outcomes. Thus, CTC clusters are derived from multicellular groupings of primary tumor cells held together through plakoglobin-dependent intercellular adhesion, and though rare, they greatly contribute to the metastatic spread of cancer.

Indexed as

AnimalsBreast NeoplasmsCell Line, TumorDisease Models, AnimalFemalegamma CateninHumansMaleMiceMice, Inbred NODMice, SCIDNeoplasm MetastasisNeoplastic Cells, CirculatingProstatic NeoplasmsSequence Analysis, RNASingle-Cell Analysisgamma Catenin

Identifiers

PMID25171411
PMCPMC4149753
OpenAlexW1993913242

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.