Evidence map›Paper›PMID 22934846›Full record

ArticleCurrent molecular medicine2013

ROCK1 & 2 perform overlapping and unique roles in angiogenesis and angiosarcoma tumor progression.

J Montalvo, C Spencer, A Hackathorn, K Masterjohn, A Perkins, C Doty, A Arumugam, P P Ongusaha, R Lakshmanaswamy, J K Liao and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Current molecular medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

30 citing papers in PubMed, 36 citations in OpenAlex.

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  14. Possible cooption of a VEGF-driven tubulogenesis program for biomineralization in echinoderms.Proceedings of the National Academy of Sciences of the United States of America · 2019
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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

12 authors at 5 institutions in 1 country.

J MontalvoGhosh Science and Technology Center, Department of Biology, Worcester State University, Worcester, Massachusetts, USA.
C Spencer
A Hackathorn
K Masterjohn
A Perkins
C Doty
A Arumugam
P P Ongusaha
R Lakshmanaswamy
J K Liao
D C Mitchell
B A Bryan
Worcester State University · USHarvard University · USTexas Tech University Health Sciences Center · USTexas Tech University · USUniversity of Massachusetts Chan Medical School · US

Funding

Tissue AnalysesP01HL048743 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI GLADYSHEV, VADIM N. · 1992 to 2014
$26.3M
TRIGEMINOVASCULAR CONTROL OF CEREBRAL BLOOD VESSELSP50NS010828 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI LIAO, JAMES KUANG-JAN · 1985 to 2007
$10.8M
LIPOPROTEINS EFFECTS ON G PROTEIN FUNCTIONR01HL052233 · NHLBI · UNIVERSITY OF CHICAGO · PI LIAO, JAMES KUANG-JAN · 1995 to 2016
$5.3M
Activation of eNOS by Steroid HormonesR01HL070274 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI LIAO, JAMES KUANG-JAN · 2002 to 2006
$2.2M
Role of PI3-Kinase in Estrogen-induced eNOS ActivationR01DK062729 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI LIAO, JAMES KUANG-JAN · 2003 to 2007
$1.9M
Novel Signaling Pathways in Ischemic StrokeR01NS070001 · NINDS · UNIVERSITY OF CHICAGO · PI LIAO, JAMES KUANG-JAN · 2010 to 2014
$1.8M
ROCK and ObesityR01DK085006 · NIDDK · UNIVERSITY OF CHICAGO · PI LIAO, JAMES KUANG-JAN · 2010 to 2014
$1.7M
Endothelial Akt in Vascular InjuryR01HL080187 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI LIAO, JAMES KUANG-JAN · 2006 to 2009
$1.6M
Role of protein kinase Akt in cerebral ischemiaP01NS010828 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI HYMAN, BRADLEY T. · 1989 to 2008
$1.4M
The Role of VEGF-stimulated Rhoa/ROCK2 Signaling in Blood Vessel FormationR15HL098931 · NHLBI · WORCESTER STATE COLLEGE · PI BRYAN, BRAD ALLEN · 2010 to 2010
$206k
NHLBI NIH HHS HL052233NHLBI NIH HHS HL098931NHLBI NIH HHS P01 HL048743NHLBI NIH HHS R01 HL052233NHLBI NIH HHS R01 HL070274NHLBI NIH HHS R01 HL080187NHLBI NIH HHS R15 HL098931NIDDK NIH HHS R01 DK062729NIDDK NIH HHS R01 DK085006NINDS NIH HHS P01 NS010828NINDS NIH HHS P50 NS010828NINDS NIH HHS R01 NS070001
6 · The paper itself

Abstract

The serine/threonine protein kinase paralogs ROCK1 & 2 have been implicated as essential modulators of angiogenesis; however their paralog-specific roles in endothelial function are unknown. shRNA knockdown of ROCK1 or 2 in endothelial cells resulted in a significant disruption of in vitro capillary network formation, cell polarization, and cell migration compared to cells harboring non-targeting control shRNA plasmids. Knockdowns led to alterations in cytoskeletal dynamics due to ROCK1 & 2-mediated reductions in actin isoform expression, and ROCK2-specific reduction in myosin phosphatase and cofilin phosphorylation. Knockdowns enhanced cell survival and led to ROCK1 & 2-mediated reduction in caspase 6 and 9 cleavage, and a ROCK2-specific reduction in caspase 3 cleavage. Microarray analysis of ROCK knockdown lines revealed overlapping and unique control of global transcription by the paralogs, and a reduction in the transcriptional regulation of just under 50% of VEGF responsive genes. Finally, paralog knockdown in xenograft angiosarcoma tumors resulted in a significant reduction in tumor formation. Our data reveals that ROCK1 & 2 exhibit overlapping and unique roles in normal and dysfunctional endothelial cells, that alterations in cytoskeletal dynamics are capable of overriding mitogen activated transcription, and that therapeutic targeting of ROCK signaling may have profound impacts for targeting angiogenesis.

Indexed as

AnimalsCell LineCell Line, TumorCell MovementCell SurvivalEndothelial CellsGene Expression RegulationGene Knockdown TechniquesHemangiosarcomaMelanomaMiceNeovascularization, Physiologicrho-Associated KinasesRNA, Small InterferingVascular Endothelial Growth Factor AXenograft Model Antitumor Assaysrho-Associated KinasesRNA, Small InterferingRock1 protein, mouseRock2 protein, mouseVascular Endothelial Growth Factor A

Identifiers

PMID22934846
PMCPMC3580831
OpenAlexW2121812509

What OpenQuestion holds

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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.