Evidence map›Paper›PMID 26975850›Full record

ArticleThe Journal of cell biology2016

Loss of miR-203 regulates cell shape and matrix adhesion through ROBO1/Rac/FAK in response to stiffness.

Lily Thao-Nhi Le, Oscar Cazares, Janna K Mouw, Sharmila Chatterjee, Hector Macias, Angel Moran, Jillian Ramos, Patricia J Keely, Valerie M Weaver, Lindsay Hinck

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of cell biology, 2016. 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
3.4field-weighted citation impact, top 8% 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

24 citing papers in PubMed, 41 citations in OpenAlex.

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  20. Feeling Stress: The Mechanics of Cancer Progression and Aggression.Frontiers in cell and developmental biology · 2018
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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

10 authors at 3 institutions in 1 country.

Lily Thao-Nhi LeDepartment of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064.
Oscar CazaresDepartment of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064.
Janna K MouwDepartment of Surgery and Center for Bioengineering and Tissue Regeneration, University of California, San Francisco, San Francisco, CA 94143.
Sharmila ChatterjeeDepartment of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064.
Hector MaciasDepartment of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064.
Angel MoranDepartment of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064.
Jillian RamosDepartment of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064.
Patricia J KeelyDepartment of Cellular and Regenerative Biology, University of Wisconsin-Madison, Madison, WI 53706.
Valerie M WeaverDepartment of Surgery and Center for Bioengineering and Tissue Regeneration, University of California, San Francisco, San Francisco, CA 94143.
Lindsay HinckDepartment of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064 lhinck@ucsc.edu.
University of California, Santa Cruz · USUniversity of California, San Francisco · USUniversity of Wisconsin–Madison · US

Funding

UNIVERSITY OF CALIFORNIA, SANTA CRUZ IMSD PROGRAMR25GM058903 · NIGMS · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI JURICA, MELISSA S · 1999 to 2019
$12.2M
Mechanisms Of Cell Migration On 3D Aligned MatricesR01CA142833 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI FRIEDL, ANDREAS, HAHN, KLAUS M. · 2010 to 2020
$3.4M
Tension-Stat3-miR-mediated metastasisR01CA192914 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SEEWALDT, VICTORIA L., WEAVER, VALERIE MARIE · 2015 to 2019
$2.9M
RE: Regulation of mammary branching morphogenesis by Slit/Robo 1 signalingR01GM098897 · NIGMS · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI HINCK, LINDSAY E · 2011 to 2014
$1.6M
Biophysical Regulation of Breast DifferentiationR01CA114462 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI KEELY, PATRICIA J · 2010 to 2014
$1.5M
NCI NIH HHS CA114462NCI NIH HHS CA142833NCI NIH HHS R01 CA114462NCI NIH HHS R01 CA142833NCI NIH HHS R01 CA192914NIGMS NIH HHS GM-098897NIGMS NIH HHS GM098897-02S1NIGMS NIH HHS R01 GM098897NIGMS NIH HHS R25 GM058903
6 · The paper itself

Abstract

Breast tumor progression is accompanied by changes in the surrounding extracellular matrix (ECM) that increase stiffness of the microenvironment. Mammary epithelial cells engage regulatory pathways that permit dynamic responses to mechanical cues from the ECM. Here, we identify a SLIT2/ROBO1 signaling circuit as a key regulatory mechanism by which cells sense and respond to ECM stiffness to preserve tensional homeostasis. We observed that Robo1 ablation in the developing mammary gland compromised actin stress fiber assembly and inhibited cell contractility to perturb tissue morphogenesis, whereas SLIT2 treatment stimulated Rac and increased focal adhesion kinase activity to enhance cell tension by maintaining cell shape and matrix adhesion. Further investigation revealed that a stiff ECM increased Robo1 levels by down-regulating miR-203. Consistently, patients whose tumor expressed a low miR-203/high Robo1 expression pattern exhibited a better overall survival prognosis. These studies show that cells subjected to stiffened environments up-regulate Robo1 as a protective mechanism that maintains cell shape and facilitates ECM adherence.

Indexed as

AnimalsCell AdhesionCell Line, TumorCell ShapeCellular MicroenvironmentDown-RegulationEpithelial CellsExtracellular MatrixFocal Adhesion Kinase 1HomeostasisHumansIntercellular Signaling Peptides and ProteinsMammary Glands, HumanMiceMicroRNAsMorphogenesisFocal Adhesion Kinase 1Intercellular Signaling Peptides and ProteinsMicroRNAsMIRN203 microRNA, humanNerve Tissue ProteinsPTK2 protein, humanrac GTP-Binding ProteinsReceptors, ImmunologicRoundabout ProteinsSlit Homolog 2 Protein

Identifiers

PMID26975850
PMCPMC4792073
OpenAlexW2301901887

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.