Evidence map›Paper›PMID 19896381›Full record

ArticleCurrent biology : CB2009

ARF6-regulated shedding of tumor cell-derived plasma membrane microvesicles.

Vandhana Muralidharan-Chari, James Clancy, Carolyn Plou, Maryse Romao, Philippe Chavrier, Graca Raposo, Crislyn D'Souza-Schorey

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Current biology : CB, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 532 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
532citing papers in PubMed, 1 pooled it
5.7field-weighted citation impact, top 3% 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

532 citing papers in PubMed, 1 synthesis or guideline pooled it, 852 citations in OpenAlex.

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472 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Vandhana Muralidharan-ChariDepartment of Biological Sciences, University of Notre Dame, IN 46556, USA.
James Clancy
Carolyn Plou
Maryse Romao
Philippe Chavrier
Graca Raposo
Crislyn D'Souza-Schorey
University of Notre Dame · USInstitut Curie · FR

Funding

Molecular Mechanisms of Cell InvasionR01CA115316 · NCI · UNIVERSITY OF NOTRE DAME · PI D'SOUZA-SCHOREY, CRISLYN · 2011 to 2016
$1.5M
Molecular Mechanisms of Cell InvasionR56CA115316 · NCI · UNIVERSITY OF NOTRE DAME · PI D'SOUZA-SCHOREY, CRISLYN · 2007 to 2008
$420k
NCI NIH HHS CA115316NCI NIH HHS R01 CA115316NCI NIH HHS R56 CA115316
6 · The paper itself

Abstract

backgroundIncreased mitogen-activated protein kinase (MAPK) signaling, small GTPase activation, cytoskeletal rearrangements, and the directed targeting of proteases to sites of extracellular matrix degradation all accompany the process of tumor cell invasion. Several studies have implicated the small GTP-binding protein ARF6 in tumor cell invasion, although the molecular basis by which ARF6 facilitates this process is unclear.

resultsWe show that the ARF6 GTP/GDP cycle regulates the release of protease-loaded plasma membrane-derived microvesicles from tumor cells into the surrounding environment. To enable microvesicle shedding, ARF6-GTP-dependent activation of phospholipase D promotes the recruitment of the extracellular signal-regulated kinase (ERK) to the plasma membrane where, in turn, ERK phosphorylates and activates myosin light-chain kinase (MLCK). MLCK-mediated MLC phosphorylation is required for microvesicle release. Inhibition of ARF6 activation is accompanied by PKC-mediated phosphorylation of MLC, which blocks microvesicle shedding. Protein cargo appears to be selectively sorted into microvesicles, and adhesion to the extracellular matrix (ECM) is facilitated by microvesicle-associated integrin receptors.

conclusionsMicrovesicle shedding in tumor cells occurs via an actomyosin-based membrane abscission mechanism that is regulated by nucleotide cycling on ARF6. Microvesicle shedding appears to release selected cellular components, particularly those involved in cell adhesion and motility, into the surrounding environment. These findings suggest that ARF6 activation and the proteolytic activities of microvesicles, both of which are thought to correlate directly with tumor progression, could potentially serve as biomarkers for disease.

Indexed as

ADP-Ribosylation Factor 6ADP-Ribosylation FactorsCell MembraneHumansNeoplasm InvasivenessADP-Ribosylation Factor 6ADP-Ribosylation FactorsARF6 protein, human

Identifiers

PMID19896381
PMCPMC3150487
OpenAlexW2009649000

What OpenQuestion holds

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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.