Evidence map›Paper›PMID 25261370›Full record

ArticleOncotarget2014

Loss of the obscurin-RhoGEF downregulates RhoA signaling and increases microtentacle formation and attachment of breast epithelial cells.

Nicole A Perry, Michele I Vitolo, Stuart S Martin, Aikaterini Kontrogianni-Konstantopoulos

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.0field-weighted citation impact, top 16% 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

26 citing papers in PubMed, 32 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. The varied functions of the giant muscle scaffold protein obscurin.Frontiers in cell and developmental biology · 2025
    Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  11. Review
  12. Article
  13. Article
  14. Obscurin: A multitasking giant in the fight against cancer.Biochimica et biophysica acta. Reviews on cancer · 2021
    Review
  15. Article
  16. Article
  17. Unraveling obscurins in heart disease.Pflugers Archiv : European journal of physiology · 2019
    Review
  18. Article
  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

4 authors at 2 institutions in 1 country.

Nicole A PerryDepartment of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD.
Michele I VitoloDepartment of Physiology, University of Maryland School of Medicine, Baltimore, MD. Marlene and Stewart Greenebaum National Cancer Institute Cancer Center, University of Maryland School of Medicine, Baltimore, MD.
Stuart S MartinDepartment of Physiology, University of Maryland School of Medicine, Baltimore, MD. Marlene and Stewart Greenebaum National Cancer Institute Cancer Center, University of Maryland School of Medicine, Baltimore, MD.
Aikaterini Kontrogianni-KonstantopoulosDepartment of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD. Marlene and Stewart Greenebaum National Cancer Institute Cancer Center, University of Maryland School of Medicine, Baltimore, MD.
National Cancer Institute · USUniversity of Maryland, Baltimore · US

Funding

UNIVERSITY OF MARYLAND GREENEBAUM CANCER CENTERSUPPORT GRANTP30CA134274 · NCI · UNIVERSITY OF MARYLAND BALTIMORE · PI FEYRUZ VIRGILIA RASSOOL · 2008 to 2026
$51.0M
TRANS NETWORK PROJECTSU54CA143868 · NCI · JOHNS HOPKINS UNIVERSITY · PI SEMENZA, GREGG L · 2009 to 2013
$13.7M
Targeting microtubule stabilization to reduce breast tumor metastasisR01CA154624 · NCI · UNIVERSITY OF MARYLAND BALTIMORE · PI MARTIN, STUART S · 2012 to 2023
$3.4M
PTEN loss increases efficiency of breast tumor metastasisK01CA166576 · NCI · UNIVERSITY OF MARYLAND BALTIMORE · PI VITOLO, MICHELE I · 2013 to 2017
$524k
NCI NIH HHS K01 CA166576NCI NIH HHS P30 CA134274NCI NIH HHS R01 CA154624NCI NIH HHS R01-CA154624NCI NIH HHS U54 CA143868NCI NIH HHS U54CA143868
6 · The paper itself

Abstract

Obscurins are RhoGEF-containing proteins whose downregulation has been implicated in the development and progression of breast cancer. Herein, we aim to elucidate the mechanism for increased motility of obscurin-deficient cells. We show that shRNA-mediated obscurin downregulation in MCF10A cells leads to >50% reduction in RhoA activity relative to scramble control (shCtrl), as well as decreased phosphorylation of RhoA effectors, including myosin light chain phosphatase, myosin light chain, lim kinase, and cofilin, in both attached and suspended cells. These alterations result in decreased actomyosin contractility, allowing suspended cells to escape detachment-induced apoptosis. Moreover, ~40% of shObsc-expressing cells, but only ~10% of shCtrl-expressing cells, extend microtentacles, tubulin-based projections that mediate the attachment of circulating tumor cells to endothelium. Indeed, we show that MCF10A cells expressing shObsc attach in vitro more readily than shCtrl cells, an advantage that persists following taxane exposure. Overall, our data suggest that loss of obscurins may represent a substantial selective advantage for breast epithelial cells during metastasis, and that treatment with paclitaxel may exacerbate this advantage by preferentially allowing obscurin-deficient, stem-like cells to attach to the endothelium of distant sites, a first step towards colonizing metastatic tumors.

Indexed as

Cell AdhesionSignal TransductionAntineoplastic AgentsApoptosisBreast NeoplasmsCell Line, TumorCell MovementCell Surface ExtensionsCytoskeletonDose-Response Relationship, DrugDown-RegulationEpithelial CellsFemaleGene Expression Regulation, NeoplasticHumansNeoplasm MetastasisAntineoplastic AgentsOBSCN protein, humanPaclitaxelProtein Serine-Threonine KinasesrhoA GTP-Binding ProteinRHOA protein, humanRho Guanine Nucleotide Exchange FactorsTubulinTubulin Modulators

Identifiers

PMID25261370
PMCPMC4226704
OpenAlexW1798190422

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.