Evidence map›Paper›PMID 39225101›Full record

ArticleThe Journal of clinical investigation2024

Single-cell analysis of breast cancer metastasis reveals epithelial-mesenchymal plasticity signatures associated with poor outcomes.

Juliane Winkler, Weilun Tan, Catherine Mm Diadhiou, Christopher S McGinnis, Aamna Abbasi, Saad Hasnain, Sophia Durney, Elena Atamaniuc, Daphne Superville, Leena Awni and 17 more

Abstract read
In one paragraph

Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
–field-weighted citation impact
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

24 citing papers in PubMed.

  1. Trial
  2. Article
  3. Article
  4. Review
  5. Regulation of PSAT1 and PHGDH by m6A in endocrine-resistant breast cancer cells.Biochimica et biophysica acta. Molecular basis of disease · 2026
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. LMO2 Regulates Epithelial-Mesenchymal Plasticity of Mammary Epithelial Cells.Journal of mammary gland biology and neoplasia · 2026
    Article
  12. Targeting tumor transition windows.Exploration of targeted anti-tumor therapy · 2026
    Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Review
  18. MUW researcher of the month: Dr.in Juliane Winkler.Wiener klinische Wochenschrift · 2025
    Article
  19. Article
  20. Review
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

27 authors.

Juliane WinklerDepartment of Anatomy and.
Weilun TanChan Zuckerberg Biohub SF, San Francisco, California, USA.
Catherine Mm DiadhiouDepartment of Anatomy and.
Christopher S McGinnisDepartment of Pharmaceutical Chemistry, UCSF, San Francisco, California, USA.
Aamna AbbasiDepartment of Anatomy and.
Saad HasnainDepartment of Anatomy and.
Sophia DurneyDepartment of Cell and Tissue Biology, UCSF, San Francisco, California, USA.
Elena AtamaniucDepartment of Cell and Tissue Biology, UCSF, San Francisco, California, USA.
Daphne SupervilleDepartment of Cell and Tissue Biology, UCSF, San Francisco, California, USA.
Leena AwniDepartment of Anatomy and.
Joyce V LeeDepartment of Cell and Tissue Biology, UCSF, San Francisco, California, USA.
Johanna H HinrichsDepartment of Anatomy and.
Patrick S WagnerCenter for Cancer Research, Medical University of Vienna, Vienna, Austria.
Namrata SinghCenter for Cancer Research, Medical University of Vienna, Vienna, Austria.
Marco Y HeinChan Zuckerberg Biohub SF, San Francisco, California, USA.
Michael BorjaChan Zuckerberg Biohub SF, San Francisco, California, USA.
Angela M DetweilerChan Zuckerberg Biohub SF, San Francisco, California, USA.
Su-Yang LiuDepartment of Anatomy and.
Ankitha NanjarajDepartment of Anatomy and.
Vaishnavi SitaramaDepartment of Anatomy and.
Hope S RugoHelen Diller Family Comprehensive Cancer Center, UCSF, San Francisco, California, USA.
Norma NeffChan Zuckerberg Biohub SF, San Francisco, California, USA.
Zev J GartnerDepartment of Pharmaceutical Chemistry, UCSF, San Francisco, California, USA.
Angela Oliveira PiscoChan Zuckerberg Biohub SF, San Francisco, California, USA.
Andrei GogaDepartment of Cell and Tissue Biology, UCSF, San Francisco, California, USA.
Spyros DarmanisChan Zuckerberg Biohub SF, San Francisco, California, USA.
Zena WerbDepartment of Anatomy and.

Funding

Research BaseP30DK063720 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GERMAN, MICHAEL S · 2003 to 2019
$21.8M
Molecular and Cellular Mechanisms in CancerT32CA108462 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GOGA, ANDREI · 2004 to 2024
$10.4M
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
Uncovering Mechanisms of Regulation and Dependency on Fatty Acid Oxidation in MYC-Driven TumorsR01CA223817 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GOGA, ANDREI · 2018 to 2022
$1.8M
Defining a novel subset of metastasis-associated monocytesF31CA284749 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SUPERVILLE, DAPHNE A · 2023 to 2024
$91k
Interrogating Immunomodulation for Anti-Metastatic TherapyF31CA257349 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MCGINNIS, CHRISTOPHER · 2021 to 2021
$26k
NCI NIH HHS F31 CA257349NCI NIH HHS F31 CA284749NCI NIH HHS R01 CA223817NCI NIH HHS T32 CA108462NCI NIH HHS U01 CA199315NIDDK NIH HHS P30 DK063720
6 · The paper itself

Abstract

Metastasis is the leading cause of cancer-related deaths. It is unclear how intratumor heterogeneity (ITH) contributes to metastasis and how metastatic cells adapt to distant tissue environments. The study of these adaptations is challenged by the limited access to patient material and a lack of experimental models that appropriately recapitulate ITH. To investigate metastatic cell adaptations and the contribution of ITH to metastasis, we analyzed single-cell transcriptomes of matched primary tumors and metastases from patient-derived xenograft models of breast cancer. We found profound transcriptional differences between the primary tumor and metastatic cells. Primary tumors upregulated several metabolic genes, whereas motility pathway genes were upregulated in micrometastases, and stress response signaling was upregulated during progression. Additionally, we identified primary tumor gene signatures that were associated with increased metastatic potential and correlated with patient outcomes. Immune-regulatory control pathways were enriched in poorly metastatic primary tumors, whereas genes involved in epithelial-mesenchymal transition were upregulated in highly metastatic tumors. We found that ITH was dominated by epithelial-mesenchymal plasticity (EMP), which presented as a dynamic continuum with intermediate EMP cell states characterized by specific genes such as CRYAB and S100A2. Elevated expression of an intermediate EMP signature correlated with worse patient outcomes. Our findings identified inhibition of the intermediate EMP cell state as a potential therapeutic target to block metastasis.

Indexed as

Breast NeoplasmsEpithelial-Mesenchymal TransitionNeoplasm MetastasisSingle-Cell AnalysisAnimalsCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansMiceNeoplasm ProteinsTranscriptomeNeoplasm ProteinsBioinformaticsBreast cancerOncology

Identifiers

PMID39225101
PMCPMC11364385

What OpenQuestion holds

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Registered trials

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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.