Evidence map›Paper›PMID 24704824›Full record

ArticleOncogene2015

KAP regulates ROCK2 and Cdk2 in an RNA-activated glioblastoma invasion pathway.

H Li, X Jiang, Y Yu, W Huang, H Xing, N Y Agar, H W Yang, B Yang, R S Carroll, M D Johnson

Abstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.7field-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

19 citing papers in PubMed, 29 citations in OpenAlex.

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  16. Novel Insights into the Roles of Rho Kinase in Cancer.Archivum immunologiae et therapiae experimentalis · 2016
    Review
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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

10 authors at 3 institutions in 2 countries.

H Li1] Department of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA [2] Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
X JiangDepartment of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Y YuDepartment of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
W HuangDepartment of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
H XingDepartment of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
N Y AgarDepartment of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
H W YangDepartment of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
B YangDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
R S CarrollDepartment of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
M D Johnson1] Department of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA [2] Program in Neuro-Oncology, Dana Farber/Brigham and Women's Cancer Center, Boston, MA, USA.
Harvard University · USBrigham and Women's Hospital · USFirst Affiliated Hospital of Zhengzhou University · CN

Funding

MicroRNA Biogenesis and the Cancer ProteomeDP2OD002319 · OD · BRIGHAM AND WOMEN'S HOSPITAL · PI JOHNSON, MARK D · 2007 to 2007
$2.6M
Preventing Glioma Cancer Stem Cell Dispersal Using Cdc2 Kinase InhibitorsR01NS062219 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI JOHNSON, MARK D · 2010 to 2014
$1.8M
NIH HHS DP2OD002319NINDS NIH HHS R01 NS062219
6 · The paper itself

Abstract

Aberrant splicing of the cyclin-dependent kinase-associated phosphatase, KAP, promotes glioblastoma invasion in a Cdc2-dependent manner. However, the mechanism by which this occurs is unknown. Here we show that miR-26a, which is often amplified in glioblastoma, promotes invasion in phosphatase and tensin homolog (PTEN)-competent and PTEN-deficient glioblastoma cells by directly downregulating KAP expression. Mechanistically, we find that KAP binds and activates ROCK2. Thus, RNA-mediated downregulation of KAP leads to decreased ROCK2 activity and this, in turn, increases Rac1-mediated invasion. In addition, the decrease in KAP expression activates the cyclin-dependent kinase, Cdk2, and this directly promotes invasion by increasing retinoblastoma phosphorylation, E2F-dependent Cdc2 expression and Cdc2-mediated inactivation of the actomyosin inhibitor, caldesmon. Importantly, glioblastoma cell invasion mediated by this pathway can be antagonized by Cdk2/Cdc2 inhibitors in vitro and in vivo. Thus, two distinct RNA-based mechanisms activate this novel KAP/ROCK2/Cdk2-dependent invasion pathway in glioblastoma.

Indexed as

ActomyosinBrain NeoplasmsCalmodulin-Binding ProteinsCDC2 Protein KinaseCell Line, TumorCyclin-Dependent Kinase 2Cyclin-Dependent Kinase Inhibitor ProteinsCyclin-Dependent KinasesDual-Specificity PhosphatasesE2F Transcription FactorsEnzyme ActivationGlioblastomaHumansMicroRNAsNeoplasm InvasivenessPhosphorylationActomyosinCalmodulin-Binding ProteinsCDC2 Protein KinaseCDK1 protein, humanCDK2 protein, humanCDKN3 protein, humanCyclin-Dependent Kinase 2Cyclin-Dependent Kinase Inhibitor ProteinsCyclin-Dependent KinasesDual-Specificity PhosphatasesE2F Transcription FactorsMicroRNAsMIRN26 microRNA, humanPTEN PhosphohydrolasePTEN protein, humanrac1 GTP-Binding ProteinRAC1 protein, humanRetinoblastoma Proteinrho-Associated KinasesRNA, Small InterferingROCK2 protein, human

Identifiers

PMID24704824
OpenAlexW2044477890

What OpenQuestion holds

Textmetadata
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.