Evidence map›Paper›PMID 36630496›Full record

ArticleScience advances2023

Cytokinesis machinery promotes cell dissociation from collectively migrating strands in confinement.

Robert A Law, Alexander Kiepas, Habben E Desta, Emiliano Perez Ipiña, Maria Parlani, Se Jong Lee, Christopher L Yankaskas, Runchen Zhao, Panagiotis Mistriotis, Nianchao Wang and 5 more

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

Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
7.1field-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

21 citing papers in PubMed, 34 citations in OpenAlex.

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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

15 authors at 2 institutions in 2 countries.

Robert A LawDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.ORCID 0000-0002-2904-4889
Alexander KiepasDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.ORCID 0000-0001-8169-3897
Habben E DestaDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.ORCID 0000-0002-0328-9597
Emiliano Perez IpiñaWilliam H. Miller III Department of Physics and Astronomy, Johns Hopkins University, Baltimore, MD 21218, USA.ORCID 0000-0002-1664-0411
Maria ParlaniDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0002-2901-5527
Se Jong LeeDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Christopher L YankaskasDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.ORCID 0000-0002-9102-4213
Runchen ZhaoDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.ORCID 0000-0001-8673-3990
Panagiotis MistriotisDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.ORCID 0000-0002-8069-3278
Nianchao WangDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Zhizhan GuDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.ORCID 0000-0001-9934-5209
Petr KalabDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.ORCID 0000-0002-8145-7728
Peter FriedlDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0002-0119-4041
Brian A CamleyWilliam H. Miller III Department of Physics and Astronomy, Johns Hopkins University, Baltimore, MD 21218, USA.ORCID 0000-0002-0765-6956
Konstantinos KonstantopoulosDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.ORCID 0000-0003-2623-1459
Johns Hopkins University · USThe University of Texas MD Anderson Cancer Center · US

Funding

The Role of Physical Cues in Collective Cell InvasionU54CA210173 · NCI · JOHNS HOPKINS UNIVERSITY · PI GERECHT, SHARON · 2016 to 2020
$9.9M
Development of high throughput screening technologies in breast cancerR01CA183804 · NCI · JOHNS HOPKINS UNIVERSITY · PI KONSTANTOPOULOS, KONSTANTINOS, KONTROGIANNI-KONSTANTOPOULOS, AIKATERINI · 2015 to 2019
$3.5M
Physical insights into cell migrationR35GM142847 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI Brian A Camley · 2021 to 2026
$2.4M
Cell mechanoresponses in physiologically relevant microenvironmentsR35GM147101 · NIGMS · AUBURN UNIVERSITY AT AUBURN · PI Panagiotis Mistriotis · 2022 to 2026
$2.1M
Cell mechanobiology in confinement using an integration of bioengineering, materials systems and in vivo modelsR01GM142175 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI KONSTANTOPOULOS, KONSTANTINOS · 2021 to 2024
$1.8M
NCI NIH HHS R01 CA183804NCI NIH HHS U54 CA210173NIGMS NIH HHS R01 GM142175NIGMS NIH HHS R35 GM142847NIGMS NIH HHS R35 GM147101
6 · The paper itself

Abstract

Cells tune adherens junction dynamics to regulate epithelial integrity in diverse (patho)physiological processes, including cancer metastasis. We hypothesized that the spatially confining architecture of peritumor stroma promotes metastatic cell dissemination by remodeling cell-cell adhesive interactions. By combining microfluidics with live-cell imaging, FLIM/FRET biosensors, and optogenetic tools, we show that confinement induces leader cell dissociation from cohesive ensembles. Cell dissociation is triggered by myosin IIA (MIIA) dismantling of E-cadherin cell-cell junctions, as recapitulated by a mathematical model. Elevated MIIA contractility is controlled by RhoA/ROCK activation, which requires distinct guanine nucleotide exchange factors (GEFs). Confinement activates RhoA via nucleocytoplasmic shuttling of the cytokinesis-regulatory proteins RacGAP1 and Ect2 and increased microtubule dynamics, which results in the release of active GEF-H1. Thus, confining microenvironments are sufficient to induce cell dissemination from primary tumors by remodeling E-cadherin cell junctions via the interplay of microtubules, nuclear trafficking, and RhoA/ROCK/MIIA pathway and not by down-regulating E-cadherin expression.

Indexed as

CytokinesisIntercellular JunctionsCadherinsHumansMicrotubulesRho Guanine Nucleotide Exchange FactorsCadherinsRho Guanine Nucleotide Exchange Factors

Identifiers

PMID36630496
PMCPMC9833664
OpenAlexW4315754322

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.