Evidence map›Paper›PMID 35480877›Full record

ArticleFrontiers in molecular biosciences2022

Nrf2 Modulates the Hybrid Epithelial/Mesenchymal Phenotype and Notch Signaling During Collective Cancer Migration.

Samuel A Vilchez Mercedes, Federico Bocci, Mona Ahmed, Ian Eder, Ninghao Zhu, Herbert Levine, José N Onuchic, Mohit Kumar Jolly, Pak Kin Wong

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

Article in Frontiers in molecular biosciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
3.9field-weighted citation impact, top 5% 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

28 citing papers in PubMed, 40 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Review
  6. Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Cancer spreading patterns based on epithelial-mesenchymal plasticity.Frontiers in cell and developmental biology · 2024
    Article
  14. Review
  15. The Role of TGF-β during Pregnancy and Pregnancy Complications.International journal of molecular sciences · 2023
    Review
  16. Article
  17. Review
  18. Article
  19. Review
  20. Long noncoding RNA MALAT1 is dynamically regulated in leader cells during collective cancer invasion.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
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 2 countries.

Samuel A Vilchez MercedesDepartment of Biomedical Engineering, The Pennsylvania State University, University Park, PA, United States.
Federico BocciCenter for Theoretical Biological Physics, Rice University, Houston, TX, United States.
Mona AhmedDepartment of Biomedical Engineering, The Pennsylvania State University, University Park, PA, United States.
Ian EderDepartment of Biomedical Engineering, The Pennsylvania State University, University Park, PA, United States.
Ninghao ZhuDepartment of Biomedical Engineering, The Pennsylvania State University, University Park, PA, United States.
Herbert LevineCenter for Theoretical Biological Physics , Department of Physics and Department of Bioengineering, Northeastern University, Boston, MA, United States.
José N OnuchicCenter for Theoretical Biological Physics, Rice University, Houston, TX, United States.
Mohit Kumar JollyCentre for BioSystems Science and Engineering, Indian Institute of Science, Bangalore, India.
Pak Kin WongDepartment of Biomedical Engineering, The Pennsylvania State University, University Park, PA, United States.
Pennsylvania State University · USRice University · USIndian Institute of Science Bangalore · INNortheastern University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hybrid epithelial/mesenchymal cells (E/M) are key players in aggressive cancer metastasis. It remains a challenge to understand how these cell states, which are mostly non-existent in healthy tissue, become stable phenotypes participating in collective cancer migration. The transcription factor Nrf2, which is associated with tumor progression and resistance to therapy, appears to be central to this process. Here, using a combination of immunocytochemistry, single cell biosensors, and computational modeling, we show that Nrf2 functions as a phenotypic stability factor for hybrid E/M cells by inhibiting a complete epithelial-mesenchymal transition (EMT) during collective cancer migration. We also demonstrate that Nrf2 and EMT signaling are spatially coordinated near the leading edge. In particular, computational analysis of an Nrf2-EMT-Notch network and experimental modulation of Nrf2 by pharmacological treatment or CRISPR/Cas9 gene editing reveal that Nrf2 stabilizes a hybrid E/M phenotype which is maximally observed in the interior region immediately behind the leading edge. We further demonstrate that the Nrf2-EMT-Notch network enhances Dll4 and Jagged1 expression at the leading edge, which correlates with the formation of leader cells and protruding tips. Altogether, our results provide direct evidence that Nrf2 acts as a phenotypic stability factor in restricting complete EMT and plays an important role in coordinating collective cancer migration.

Indexed as

DLL4epithelial-mesenchymal transitioninvasionjagged1leader cell

Identifiers

PMID35480877
PMCPMC9037689
OpenAlexW4225597279

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.