Evidence map›Paper›PMID 35880301›Full record

ArticleThe EMBO journal2022

ECM dimensionality tunes actin tension to modulate endoplasmic reticulum function and spheroid phenotypes of mammary epithelial cells.

FuiBoon Kai, Guanqing Ou, Richard W Tourdot, Connor Stashko, Guido Gaietta, Mark F Swift, Niels Volkmann, Alexandra F Long, Yulong Han, Hector H Huang and 11 more

Open access · bronzeAbstract read
In one paragraph

Article in The EMBO journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.5field-weighted citation impact, top 11% 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

13 citing papers in PubMed, 22 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

21 authors at 7 institutions in 4 countries.

FuiBoon KaiDepartment of Surgery, Center for Bioengineering and Tissue Regeneration, University of California San Francisco, San Francisco, CA, USA.
Guanqing OuDepartment of Surgery, Center for Bioengineering and Tissue Regeneration, University of California San Francisco, San Francisco, CA, USA.
Richard W TourdotDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
Connor StashkoDepartment of Surgery, Center for Bioengineering and Tissue Regeneration, University of California San Francisco, San Francisco, CA, USA.
Guido GaiettaScintillon Institute, San Diego, CA, USA.
Mark F SwiftScintillon Institute, San Diego, CA, USA.ORCID 0000-0001-5663-0798
Niels VolkmannScintillon Institute, San Diego, CA, USA.ORCID 0000-0003-1328-6426
Alexandra F LongTetrad Graduate Program, University of California San Francisco, San Francisco, CA, USA.
Yulong HanDepartment of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Hector H HuangDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0003-0908-9008
Jason J NortheyDepartment of Surgery, Center for Bioengineering and Tissue Regeneration, University of California San Francisco, San Francisco, CA, USA.
Andrew M LeidalDepartment of Pathology, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0002-4001-3266
Virgile ViasnoffMechanobiology Institute, National University of Singapore, Singapore City, Singapore.
David M BryantCancer Research UK Beatson Institute, Glasgow, UK.ORCID 0000-0003-2721-5012
Wei GuoDepartment of Biology, University of Pennsylvania, Philadelphia, PA, USA.
Arun P WiitaDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA.
Ming GuoDepartment of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Sophie DumontDepartment of Bioengineering and Therapeutic Sciences, Department of Cell & Tissue Biology, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0002-8283-1523
Dorit HaneinScintillon Institute, San Diego, CA, USA.ORCID 0000-0002-6072-4946
Ravi RadhakrishnanDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0003-0686-2851
Valerie M WeaverDepartment of Surgery, Center for Bioengineering and Tissue Regeneration, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0003-4786-6752
University of California, San Francisco · USUniversity of Pennsylvania · USCentre National de la Recherche Scientifique · FRMassachusetts Institute of Technology · USScintillon Institute · USCancer Research UK Scotland Institute · GBNational University of Singapore · SG

Funding

PSOC@Penn Education and OutreachU54CA193417 · NCI · UNIVERSITY OF PENNSYLVANIA · PI DISCHER, DENNIS E. · 2015 to 2020
$10.5M
Tissue mechanics reprograms the tissue to malignancy and metastasisR35CA242447 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VALERIE MARIE WEAVER · 2020 to 2026
$6.6M
Microscopy system upgradeR35GM136420 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Sophie Dumont · 2020 to 2026
$4.6M
A physical sciences approach to investigate the role of exosomes in metastatic progressionU01CA250044 · NCI · UNIVERSITY OF PENNSYLVANIA · PI GUO, WEI, RADHAKRISHNAN, RAVI · 2021 to 2025
$3.9M
Molecular Basis and Regulatory Mechanisms of Exosome SecretionR35GM141832 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI WEI GUO · 2021 to 2026
$3.9M
Epithelial layer jamming in breast cancer cell migrationU01CA202123 · NCI · HARVARD SCHOOL OF PUBLIC HEALTH · PI FREDBERG, JEFFREY J · 2015 to 2019
$3.4M
A plasticity and reprogramming paradigm for therapy resistance at the single cell levelU01CA227550 · NCI · UNIVERSITY OF PENNSYLVANIA · PI RADHAKRISHNAN, RAVI, RAJ, ARJUN · 2018 to 2022
$3.3M
ECM geometrical and mechanical properties modulate RTK signalingU01CA202241 · NCI · UNIVERSITY OF CALIFORNIA BERKELEY · PI GROVES, JAY T., WEAVER, VALERIE MARIE · 2015 to 2019
$3.3M
Tissue Tension, RANK and Breast Cancer RiskR01CA222508 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HWANG, E.SHELLEY, WEAVER, VALERIE MARIE · 2018 to 2022
$2.8M
Tools for Quantitative Analysis of Complex Systems in CryoETP01GM121203 · NIGMS · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI VOLKMANN, NIELS · 2018 to 2019
$1.9M
Instrumentation Upgrade: acquisition of an intermediate voltage TEMS10OD012372 · OD · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI HANEIN, DORIT · 2012 to 2012
$1.9M
Medical Research Council MR/T040769/1NCI NIH HHS R01 CA222508NCI NIH HHS R35 CA242447NCI NIH HHS U01 CA202123NCI NIH HHS U01 CA202241NCI NIH HHS U01 CA227550NCI NIH HHS U01 CA250044NCI NIH HHS U54 CA193417NIGMS NIH HHS P01 GM121203NIGMS NIH HHS R35 GM136420NIGMS NIH HHS R35 GM141832NIH HHS S10 OD012372
6 · The paper itself

Abstract

Patient-derived organoids and cellular spheroids recapitulate tissue physiology with remarkable fidelity. We investigated how engagement with a reconstituted basement membrane in three dimensions (3D) supports the polarized, stress resilient tissue phenotype of mammary epithelial spheroids. Cells interacting with reconstituted basement membrane in 3D had reduced levels of total and actin-associated filamin and decreased cortical actin tension that increased plasma membrane protrusions to promote negative plasma membrane curvature and plasma membrane protein associations linked to protein secretion. By contrast, cells engaging a reconstituted basement membrane in 2D had high cortical actin tension that forced filamin unfolding and endoplasmic reticulum (ER) associations. Enhanced filamin-ER interactions increased levels of PKR-like ER kinase effectors and ER-plasma membrane contact sites that compromised calcium homeostasis and diminished cell viability. Consequently, cells with decreased cortical actin tension had reduced ER stress and survived better. Consistently, cortical actin tension in cellular spheroids regulated polarized basement membrane membrane deposition and sensitivity to exogenous stress. The findings implicate cortical actin tension-mediated filamin unfolding in ER function and underscore the importance of tissue mechanics in organoid homeostasis.

Indexed as

ActinsEndoplasmic ReticulumEndoplasmic Reticulum StressEpithelial CellsFilaminsPhenotypeActinsFilaminsactin tensionendoplasmic reticulumextracellular matrixmembrane contact sitesspheroids

Identifiers

PMID35880301
PMCPMC9434103
OpenAlexW4287922209

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.