Evidence map›Paper›PMID 24642616›Full record

ArticleBritish journal of cancer2014

Restoration of PPP2CA expression reverses epithelial-to-mesenchymal transition and suppresses prostate tumour growth and metastasis in an orthotopic mouse model.

A Bhardwaj, S Singh, S K Srivastava, S Arora, S J Hyde, J Andrews, W E Grizzle, A P Singh

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

Article in British journal of cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed, 1 pooled it
6.3field-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

43 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.

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  11. Potential Role and Clinical Value of PPP2CA in Hepatocellular Carcinoma.Journal of clinical and translational hepatology · 2021
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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

8 authors at 3 institutions in 1 country.

A BhardwajDepartment of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA.
S SinghDepartment of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA.
S K SrivastavaDepartment of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA.
S AroraDepartment of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA.
S J HydeDepartment of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA.
J AndrewsDepartment of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA.
W E GrizzleDepartment of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
A P Singh1] Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA [2] Department of Biochemistry and Molecular Biology, College of Medicine, University of South Alabama, Mobile, AL 36688, USA.
University of South Alabama · USUSA Mitchell Cancer Institute · USUniversity of Alabama at Birmingham · US

Funding

Targeting tumor-stromal interaction for pancreatic cancer therapyR01CA175772 · NCI · UNIVERSITY OF SOUTH ALABAMA · PI SINGH, AJAY PRATAP · 2014 to 2018
$1.9M
NCI NIH HHS CA175772NCI NIH HHS R01 CA175772
6 · The paper itself

Abstract

backgroundEmergence of castration-resistance in prostate cancer (PCa) is invariably associated with aggressive and metastatic disease. Previously, we reported promotion of castration-resistance upon downregulation of PPP2CA (encoding catalytic subunit of protein phosphatase 2A (PP2A), α-isoform); however, its role in PCa growth and metastasis remained undetermined.

methodsPPP2CA was overexpressed/silenced in PCa cells by stable transfection. Gene expression was examined by reverse transcription polymerase chain reaction, immunoblot and immunofluorescence analyses, and transcriptional activity measured by luciferase-based promoter-reporter assay. Effect on PCa phenotype was studied in vitro and in orthotopic mouse model, and immunohistochemical/histological analyses performed to assess proliferation/apoptosis and confirm metastatic lesions.

resultsAn inverse association of PPP2CA expression was observed with epithelial-to-mesenchymal transition (EMT) and aggressive PCa phenotype. PPP2CA restoration resulted in decreased nuclear accumulation and transcriptional activity of β-catenin/NF-κB, and restitution of their activity abrogated PPP2CA-induced EMT reversal and suppression of PCa invasiveness. Akt mediated PPP2CA loss-induced nuclear accumulation of β-catenin/NF-κB through inactivation of Gsk3-β and IκB-α, respectively. Animal studies revealed a suppressive effect of PPP2CA expression on PCa growth and metastasis.

conclusionsOur findings suggest that PPP2CA downregulation serves as a molecular link between gain of castration-resistance and aggressive PCa phenotype, and its restoration could be an effective preventive/therapeutic approach against the advanced disease.

Indexed as

Molecular Targeted TherapyAnimalsDisease Models, AnimalEpithelial-Mesenchymal TransitionGene Expression Regulation, NeoplasticGene Knockdown TechniquesHumansMaleMiceNeoplasm MetastasisProstatic Neoplasms, Castration-ResistantProtein Phosphatase 2Signal TransductionPPP2CA protein, humanProtein Phosphatase 2

Identifiers

PMID24642616
PMCPMC3992501
OpenAlexW2065914207

What OpenQuestion holds

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LicenceCC BY-NC-SA
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Registered trials

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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.