Evidence map›Paper›PMID 32144411›Full record

ArticleNature cell biology2020

Transcriptional diversity and bioenergetic shift in human breast cancer metastasis revealed by single-cell RNA sequencing.

Ryan T Davis, Kerrigan Blake, Dennis Ma, Mari B Ishak Gabra, Grace A Hernandez, Anh T Phung, Ying Yang, Dustin Maurer, Austin E Y T Lefebvre, Hamad Alshetaiwi and 8 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature cell biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 214 papers.

0numbers the graph read from it
0cells of the map it votes in
214citing papers in PubMed
17.9field-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

214 citing papers in PubMed, 314 citations in OpenAlex.

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  13. Metabolism in Tumour-Induced Bone Disease.Current osteoporosis reports · 2026
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  20. Review

154 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

18 authors at 4 institutions in 2 countries.

Ryan T DavisDepartment of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA.ORCID http://orcid.org/0000-0003-0036-4085
Kerrigan BlakeCenter for Complex Biological Systems, University of California, Irvine, Irvine, CA, USA.
Dennis MaDepartment of Biological Chemistry, University of California, Irvine, Irvine, CA, USA.
Mari B Ishak GabraDepartment of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, USA.
Grace A HernandezDepartment of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA.
Anh T PhungDepartment of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA.
Ying YangDepartment of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, USA.
Dustin MaurerCenter for Complex Biological Systems, University of California, Irvine, Irvine, CA, USA.
Austin E Y T LefebvreBiomedical Engineering Department, University of California, Irvine, Irvine, CA, USA.
Hamad AlshetaiwiDepartment of Biological Chemistry, University of California, Irvine, Irvine, CA, USA.
Zhengtao XiaoDepartment of Pharmacology and Cancer Biology, Duke University, Durham, NC, USA.ORCID http://orcid.org/0000-0002-5535-5381
Juan LiuDepartment of Pharmacology and Cancer Biology, Duke University, Durham, NC, USA.
Jason W LocasaleDepartment of Pharmacology and Cancer Biology, Duke University, Durham, NC, USA.ORCID http://orcid.org/0000-0002-7766-3502
Michelle A DigmanCenter for Complex Biological Systems, University of California, Irvine, Irvine, CA, USA.
Eric MjolsnessDepartment of Computer Science, University of California, Irvine, Irvine, CA, USA.
Mei KongDepartment of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, USA.ORCID http://orcid.org/0000-0001-8139-2349
Zena WerbDepartment of Anatomy, University of California, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-6525-3872
Devon A LawsonDepartment of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA. dalawson@uci.edu.ORCID http://orcid.org/0000-0003-1692-0517
University of California, Irvine · USDuke University · USFluor (United States) · USUniversity of California, San Francisco · US

Funding

YEAST RIBOSOMAL STALK COMPOSITION IN VIVO BY TWO-PHOTON FCS AND PCH ANALYSISP41RR003155 · NCRR · UNIVERSITY OF ILLINOIS URBANA-CHAMPAIGN · PI GRATTON, ENRICO · 1986 to 2011
$14.9M
TRD4: Phasor analysisP41GM103540 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI GRATTON, ENRICO · 2012 to 2020
$12.5M
Role of Metalloproteinases in Mammary Gland RemodelingR01CA057621 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WERB, ZENA · 1993 to 2017
$9.0M
CARCINOGENESIST32CA009054 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI EDINGER, AIMEE L, FRUMAN, DAVID ALEXANDER · 1985 to 2025
$8.6M
Integrative approach to heterogeneity in breast cancer metastasisU01CA199315 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GOGA, ANDREI, SPELLMAN, PAUL T. · 2016 to 2020
$3.2M
Deciphering the gene regulatory network controlling vertebrate endodermal fatesR01HD073179 · NICHD · UNIVERSITY OF CALIFORNIA-IRVINE · PI CHO, KEN W.Y., MJOLSNESS, ERIC D · 2013 to 2017
$2.9M
Zeiss LSM 710 NLO Confocal MicroscopeS10RR027508 · NCRR · UNIVERSITY OF CALIFORNIA-IRVINE · PI DIGMAN, MICHELLE · 2011 to 2011
$594k
Single-cell analysis of intratumor heterogeneity in metastasisK22CA190511 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI LAWSON, DEVON A. · 2016 to 2018
$486k
Assessment of the phasor Fluorescence Lifetime Imaging Microscopy (FLIM) Approach in an animal model R21HD090629 · NICHD · UNIVERSITY OF CALIFORNIA-IRVINE · PI CHO, KEN W.Y., DIGMAN, MICHELLE · 2017 to 2018
$405k
NCI NIH HHS K22 CA190511NCRR NIH HHS P41 RR003155NCRR NIH HHS S10 RR027508NICHD NIH HHS R21 HD090629NIGMS NIH HHS P41 GM103540U.S. Department of Health & Human Services | National Institutes of Health (NIH) K22CA190511U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01HD073179U.S. Department of Health & Human Services | National Institutes of Health (NIH) T32CA009054U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA057621U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) U01CA199315
6 · The paper itself

Abstract

Although metastasis remains the cause of most cancer-related mortality, mechanisms governing seeding in distal tissues are poorly understood. Here, we establish a robust method for the identification of global transcriptomic changes in rare metastatic cells during seeding using single-cell RNA sequencing and patient-derived-xenograft models of breast cancer. We find that both primary tumours and micrometastases display transcriptional heterogeneity but micrometastases harbour a distinct transcriptome program conserved across patient-derived-xenograft models that is highly predictive of poor survival of patients. Pathway analysis revealed mitochondrial oxidative phosphorylation as the top pathway upregulated in micrometastases, in contrast to higher levels of glycolytic enzymes in primary tumour cells, which we corroborated by flow cytometric and metabolomic analyses. Pharmacological inhibition of oxidative phosphorylation dramatically attenuated metastatic seeding in the lungs, which demonstrates the functional importance of oxidative phosphorylation in metastasis and highlights its potential as a therapeutic target to prevent metastatic spread in patients with breast cancer.

Indexed as

TranscriptomeAnimalsBreast NeoplasmsEnergy MetabolismFemaleHumansMice, Inbred NODMice, SCIDMitochondriaNeoplasm MetastasisOxidative PhosphorylationSequence Analysis, RNASingle-Cell AnalysisTranscription, Genetic

Identifiers

PMID32144411
OpenAlexW3010323140

What OpenQuestion 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 OpenQuestion graph.