Evidence map›Paper›PMID 27203208›Full record

ArticleOncotarget2016

Inhibitors of Rho kinase (ROCK) signaling revert the malignant phenotype of breast cancer cells in 3D context.

Masahiro Matsubara, Mina J Bissell

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 1 pooled it
3.2field-weighted citation impact, top 9% 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

36 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Article
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  7. Review
  8. Article
  9. Review
  10. The PI3K/Akt Pathway and Glucose Metabolism: A Dangerous Liaison in Cancer.International journal of biological sciences · 2024
    Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. OncogenicScience advances · 2021
    Article
  17. Article
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  19. 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

2 authors at 1 institution in 2 countries.

Masahiro MatsubaraLife Sciences Division, Lawrence Berkeley National Laboratory, University of California, Berkeley, Berkeley, CA, USA.
Mina J BissellLife Sciences Division, Lawrence Berkeley National Laboratory, University of California, Berkeley, Berkeley, CA, USA.
Lawrence Berkeley National Laboratory · US

Funding

Definition of the Microenvironment in Breast CancerR01CA064786 · NCI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI BISSELL, MINA · 1995 to 2020
$6.1M
Definition of Microenvironment in Breast CancerR37CA064786 · NCI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI BISSELL, MINA · 2009 to 2013
$2.0M
NCI NIH HHS R01 CA064786NCI NIH HHS R37 CA064786
6 · The paper itself

Abstract

Loss of polarity and quiescence along with increased cellular invasiveness are associated with breast tumor progression. ROCK plays a central role in actin-cytoskeletal rearrangement. We used physiologically relevant 3D cultures of nonmalignant and cancer cells in gels made of laminin-rich extracellular matrix, to investigate ROCK function. Whereas expression levels of ROCK1 and ROCK2 were elevated in cancer cells compared to nonmalignant cells, this was not observed in 2D cultures. Malignant cells showed increased phosphorylation of MLC, corresponding to disorganized F-actin. Inhibition of ROCK signaling restored polarity, decreased disorganization of F-actin, and led to reduction of proliferation. Inhibition of ROCK also decreased EGFR and Integrinβ1 levels, and consequently suppressed activation of Akt, MAPK and FAK as well as GLUT3 and LDHA levels. Again, ROCK inhibition did not inhibit these molecules in 2D. A triple negative breast cancer cell line, which lacks E-cadherin, had high levels of ROCK but was less sensitive to ROCK inhibitors. Exogenous overexpression of E-cadherin, however, rendered these cells strikingly sensitive to ROCK inhibition. Our results add to the growing literature that demonstrate the importance of context and tissue architecture in determining not only regulation of normal and malignant phenotypes but also drug response.

Indexed as

Actin CytoskeletonAntigens, CDAntineoplastic AgentsBreast NeoplasmsCadherinsCancer-Associated FibroblastsCell Line, TumorCell PolarityCell ProliferationCoculture TechniquesDose-Response Relationship, DrugDrug Resistance, NeoplasmFemaleHumansMolecular Targeted TherapyPhenotypeAntigens, CDAntineoplastic AgentsCadherinsCDH1 protein, humanProtein Kinase InhibitorsrhoA GTP-Binding ProteinRHOA protein, humanrho-Associated KinasesROCK1 protein, humanROCK2 protein, humanbreast cancerinvasivenesspolarityROCKthree-dimensional culture

Identifiers

PMID27203208
PMCPMC5077963
OpenAlexW2397320069

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.