Evidence map›Paper›PMID 28903319›Full record

ArticleOncotarget2017

Loss of giant obscurins alters breast epithelial cell mechanosensing of matrix stiffness.

Kimberly M Stroka, Bin Sheng Wong, Marey Shriver, Jude M Phillip, Denis Wirtz, Aikaterini Kontrogianni-Konstantopoulos, Konstantinos Konstantopoulos

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.7field-weighted citation impact, top 18% 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

20 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  7. Article
  8. Article
  9. Obscurin: A multitasking giant in the fight against cancer.Biochimica et biophysica acta. Reviews on cancer · 2021
    Review
  10. Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Obscurin is a semi-flexible molecule in solution.Protein science : a publication of the Protein Society · 2019
    Article
  16. Article
  17. Review
  18. Article
  19. Astrocytes from the brain microenvironment alter migration and morphology of metastatic breast cancer cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017
    Article
  20. 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

7 authors at 4 institutions in 1 country.

Kimberly M StrokaFischell Department of Bioengineering, University of Maryland, College Park, MD, 20742, USA.
Bin Sheng WongJohns Hopkins Institute for NanoBioTechnology, The Johns Hopkins University, Baltimore, MD, 21218, USA.
Marey ShriverUniversity of Maryland School of Medicine, Department of Biochemistry and Molecular Biology, Baltimore, MD, 21201, USA.
Jude M PhillipJohns Hopkins Institute for NanoBioTechnology, The Johns Hopkins University, Baltimore, MD, 21218, USA.
Denis WirtzJohns Hopkins Institute for NanoBioTechnology, The Johns Hopkins University, Baltimore, MD, 21218, USA.
Aikaterini Kontrogianni-KonstantopoulosUniversity of Maryland School of Medicine, Department of Biochemistry and Molecular Biology, Baltimore, MD, 21201, USA.
Konstantinos KonstantopoulosJohns Hopkins Institute for NanoBioTechnology, The Johns Hopkins University, Baltimore, MD, 21218, USA.
Johns Hopkins University · USNational Cancer Institute · USUniversity of Maryland, Baltimore · USUniversity of Maryland, College Park · US

Funding

Development of high throughput screening technologies in breast cancerR01CA183804 · NCI · JOHNS HOPKINS UNIVERSITY · PI KONSTANTOPOULOS, KONSTANTINOS, KONTROGIANNI-KONSTANTOPOULOS, AIKATERINI · 2015 to 2019
$3.5M
Pancreatic Cancer Cell Mechanics and ImagingR01CA186286 · NCI · JOHNS HOPKINS UNIVERSITY · PI KONSTANTOPOULOS, KONSTANTINOS · 2014 to 2018
$2.1M
Acquisition of Sony Biotechnology iCyt Synergy SY3200 BSC Cell SorterS10OD016230 · OD · JOHNS HOPKINS UNIVERSITY · PI MCCAFFERY, J. MICHAEL · 2014 to 2014
$520k
Role of the physical microenvironment in tumor cell migration and the cell cycleF32CA177756 · NCI · JOHNS HOPKINS UNIVERSITY · PI STROKA, KIMBERLY · 2013 to 2014
$93k
NCI NIH HHS F32 CA177756NCI NIH HHS R01 CA183804NCI NIH HHS R01 CA186286NIH HHS S10 OD016230
6 · The paper itself

Abstract

Obscurins are a family of RhoGEF-containing proteins with tumor and metastasis suppressing roles in breast epithelium. Downregulation of giant obscurins in normal breast epithelial cells leads to reduced levels of active RhoA and of its downstream effectors. Herein, we elucidate how depletion of giant obscurins affects the response of breast epithelial cells to changes in the mechanical properties of the microenvironment. We find that knockdown of obscurins increases cell morphodynamics, migration speed, and diffusivity on polyacrylamide gels of ≥ 1 kPa, presumably by decreasing focal adhesion area and density as well as cell traction forces. Depletion of obscurins also increases cell mechanosensitivity on soft (0.4-4 kPa) surfaces. Similar to downregulation of obscurins, pharmacological inhibition of Rho kinase in breast epithelial cells increases migration and morphodynamics, suggesting that suppression of Rho kinase activity following obscurin knockdown can account for alterations in morphodynamics and migration. In contrast, inhibition of myosin light chain kinase reduces morphodynamics and migration, suggesting that temporal changes in cell shape are required for efficient migration. Collectively, downregulation of giant obscurins facilitates cell migration through heterogeneous microenvironments of varying stiffness by altering cell mechanobiology.

Indexed as

cell migrationmatrix stiffnessmechanosensitivityobscurinRhoA

Identifiers

PMID28903319
PMCPMC5589558
OpenAlexW2498513289

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.