Evidence map›Paper›PMID 23382286›Full record

ArticleNeuro-oncology2013

PTEN suppresses SPARC-induced pMAPKAPK2 and inhibits SPARC-induced Ser78 HSP27 phosphorylation in glioma.

Ridwan Alam, Chad R Schultz, William A Golembieski, Laila M Poisson, Sandra A Rempel

Open access · bronzeAbstract read
In one paragraph

Article in Neuro-oncology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.3field-weighted citation impact, top 13% 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

17 citing papers in PubMed, 31 citations in OpenAlex.

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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

5 authors at 1 institution in 1 country.

Ridwan AlamBarbara Jane Levy Laboratory of Molecular Neuro-Oncology, Hermelin Brain Tumor Center, Department of Neurosurgery, Education and Research Bldg., Henry Ford Hospital, 2799 West Grand Blvd., Detroit, MI 48202, USA.
Chad R Schultz
William A Golembieski
Laila M Poisson
Sandra A Rempel
Henry Ford Hospital · US

Funding

THE ROLE OF SPARC IN GLIOMA INVASIONR01CA086997 · NCI · HENRY FORD HEALTH SYSTEM · PI REMPEL, SANDRA ANN · 2001 to 2007
$1.8M
HSP27: A modulator and therapeutic target of SPARC-induced glioma invasion.R01CA138401 · NCI · HENRY FORD HEALTH SYSTEM · PI REMPEL, SANDRA ANN · 2011 to 2015
$1.5M
NCI NIH HHS R01 CA138401NCI NIH HHS R01CA86997
6 · The paper itself

Abstract

backgroundSecreted protein acidic and rich in cysteine (SPARC) is overexpressed in astrocytomas (World Health Organization grades II-IV). We previously demonstrated that SPARC promotes glioma migration and invasion-in part, by activating the P38 mitogen-activated protein kinase (MAPK)-heat shock protein (HSP)27 signaling pathway. The commonly lost tumor suppressor phosphatase and tensin homolog (PTEN) suppresses SPARC-induced migration, which is accompanied by suppression of Shc-Ras-Raf-MEK-ERK1/2 and Akt signaling. As PTEN completely suppresses SPARC-induced migration, we proposed that PTEN must also interfere with SPARC-induced HSP27 signaling. Therefore, this study determined the effects of PTEN expression on SPARC-induced expression and phosphorylation of HSP27.

methodsControl and SPARC-expressing clones transfected with control- or PTEN-expression plasmids were plated on fibronectin-coated tissue culture plates for 3, 6, 24, and 48 h and then lysed. Equal amounts of protein were subjected to Western blot and densitometric analyses.

resultsThe results show that SPARC enhances phosphorylated (p)P38 MAPK, phosphorylated MAPK-activated protein kinase 2 (pMAPKAPK2), and serine (Ser)78 HSP27 phosphorylation relative to total HSP27. PTEN suppresses pAkt and pMAPKAPK2, suggesting that PTEN effects are downstream of pP38 MAPK. PTEN suppressed SPARC-induced sustained phosphorylation at Ser78 HSP27. As the level of total HSP27 differed based on the presence of SPARC or PTEN, the ratios of phosphorylation-specific to total HSP27 were examined. The data demonstrate that SPARC-induced phosphorylation at Ser78 remains elevated despite increasing levels of total HSP27. In contrast, PTEN inhibits SPARC-induced increases in Ser78 HSP27 phosphorylation relative to total HSP27.

conclusionThese data describe a novel mechanism whereby PTEN inhibits SPARC-induced migration through suppression and differential regulation of pAkt and the P38 MAPK-MAPKAPK2-HSP27 signaling pathway.

Indexed as

Blotting, WesternBrain NeoplasmsGliomaHSP27 Heat-Shock ProteinsHumansIntracellular Signaling Peptides and ProteinsMAP-Kinase-Activated Kinase 2Osteonectinp38 Mitogen-Activated Protein KinasesPhosphorylationProtein Serine-Threonine KinasesProto-Oncogene Proteins c-aktPTEN PhosphohydrolaseSerineSignal TransductionTumor Cells, CulturedHSP27 Heat-Shock ProteinsIntracellular Signaling Peptides and ProteinsMAP-Kinase-Activated Kinase 2Osteonectinp38 Mitogen-Activated Protein KinasesProtein Serine-Threonine KinasesProto-Oncogene Proteins c-aktPTEN PhosphohydrolasePTEN protein, humanSerineSPARC protein, humanTumor Suppressor Proteins

Identifiers

PMID23382286
PMCPMC3607267
OpenAlexW2097303895

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.