Evidence map›Paper›PMID 36253369›Full record

ArticleNature communications2022

Polarized NHE1 and SWELL1 regulate migration direction, efficiency and metastasis.

Yuqi Zhang, Yizeng Li, Keyata N Thompson, Konstantin Stoletov, Qinling Yuan, Kaustav Bera, Se Jong Lee, Runchen Zhao, Alexander Kiepas, Yao Wang and 7 more

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

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed
7.6field-weighted citation impact, top 2% 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

52 citing papers in PubMed, 69 citations in OpenAlex.

  1. Review
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  7. Cell-nanoplastics association impacts cell proliferation and motility.bioRxiv : the preprint server for biology · 2026
    Article
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  15. Chemical compensation to mechanical loss in cell mechanosensation.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  16. Review
  17. Review
  18. Review
  19. Constructing a chemokine-based model and identifyingTranslational cancer research · 2025
    Article
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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

17 authors at 5 institutions in 3 countries.

Yuqi ZhangDepartment of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, 21218, USA.
Yizeng LiDepartment of Biomedical Engineering, Binghamton University, SUNY, Binghamton, NY, 13902, USA.
Keyata N ThompsonMarlene and Stewart Greenebaum National Cancer Institute Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Konstantin StoletovDepartment of Oncology, University of Alberta, Edmonton, AB, T6G 2E1, Canada.
Qinling YuanDepartment of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, 21218, USA.
Kaustav BeraDepartment of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, 21218, USA.ORCID 0000-0002-0962-4368
Se Jong LeeDepartment of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, 21218, USA.
Runchen ZhaoDepartment of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, 21218, USA.
Alexander KiepasDepartment of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, 21218, USA.ORCID 0000-0001-8169-3897
Yao WangDepartment of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, 21218, USA.ORCID 0000-0003-0281-991X
Panagiotis MistriotisDepartment of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, 21218, USA.ORCID 0000-0002-8069-3278
Selma A SerraLaboratory of Molecular Physiology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, 08003, Barcelona, Spain.
John D LewisDepartment of Oncology, University of Alberta, Edmonton, AB, T6G 2E1, Canada.ORCID 0000-0002-7734-1204
Miguel A ValverdeLaboratory of Molecular Physiology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, 08003, Barcelona, Spain.ORCID 0000-0002-6961-3361
Stuart S MartinMarlene and Stewart Greenebaum National Cancer Institute Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.ORCID 0000-0002-4378-4381
Sean X SunDepartment of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, 21218, USA. ssun@jhu.edu.ORCID 0000-0002-9077-7088
Konstantinos KonstantopoulosDepartment of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, 21218, USA. konstant@jhu.edu.ORCID 0000-0003-2623-1459
Johns Hopkins University · USUniversitat Pompeu Fabra · ESUniversity of Alberta · CAUniversity of Maryland, Baltimore · USBinghamton University · US

Funding

The interplay of ion transporters and cytoskeleton in breast cancer migration and metastasisR01CA254193 · NCI · JOHNS HOPKINS UNIVERSITY · PI KONSTANTOPOULOS, KONSTANTINOS, MARTIN, STUART S · 2021 to 2025
$2.7M
The Role of Hydraulic Pressure in the Osmotic Engine Model of Cell MigrationR01GM134542 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI SEAN X SUN · 2019 to 2026
$2.1M
NCI NIH HHS R01 CA254193NIGMS NIH HHS R01 GM134542
6 · The paper itself

Abstract

Cell migration regulates diverse (patho)physiological processes, including cancer metastasis. According to the Osmotic Engine Model, polarization of NHE1 at the leading edge of confined cells facilitates water uptake, cell protrusion and motility. The physiological relevance of the Osmotic Engine Model and the identity of molecules mediating cell rear shrinkage remain elusive. Here, we demonstrate that NHE1 and SWELL1 preferentially polarize at the cell leading and trailing edges, respectively, mediate cell volume regulation, cell dissemination from spheroids and confined migration. SWELL1 polarization confers migration direction and efficiency, as predicted mathematically and determined experimentally via optogenetic spatiotemporal regulation. Optogenetic RhoA activation at the cell front triggers SWELL1 re-distribution and migration direction reversal in SWELL1-expressing, but not SWELL1-knockdown, cells. Efficient cell reversal also requires Cdc42, which controls NHE1 repolarization. Dual NHE1/SWELL1 knockdown inhibits breast cancer cell extravasation and metastasis in vivo, thereby illustrating the physiological significance of the Osmotic Engine Model.

Indexed as

NeoplasmsSodium-Hydrogen ExchangersCell MovementCell SizeHumansWaterSodium-Hydrogen ExchangersWater

Identifiers

PMID36253369
PMCPMC9576788
OpenAlexW4306407033

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.