Evidence map›Paper›PMID 27358402›Full record

ArticleThe Journal of biological chemistry2016

PtdIns(3,4,5)P3-dependent Rac Exchanger 1 (PREX1) Rac-Guanine Nucleotide Exchange Factor (GEF) Activity Promotes Breast Cancer Cell Proliferation and Tumor Growth via Activation of Extracellular Signal-regulated Kinase 1/2 (ERK1/2) Signaling.

Heng-Jia Liu, Lisa M Ooms, Nuthasuda Srijakotre, Joey Man, Jessica Vieusseux, JoAnne E Waters, Yue Feng, Charles G Bailey, John E J Rasko, John T Price and 1 more

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

Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

21 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
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  10. Silencing Rac1 and Prex1 Inhibit Epithelial-Mesenchymal Transition in Human Gastric Cancer Cells Induced by Transforming Growth Factor-β1.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2023
    Article
  11. Phosphoinositides in New Spaces.Cold Spring Harbor perspectives in biology · 2023
    Review
  12. Article
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  14. PtdIns(3,4,5)PProceedings of the National Academy of Sciences of the United States of America · 2020
    Article
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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

11 authors at 4 institutions in 1 country.

Heng-Jia LiuFrom the Cancer Program, Monash Biomedicine Discovery Institute, and Department of Biochemistry and Molecular Biology, Monash University, Victoria 3800, Australia.
Lisa M OomsFrom the Cancer Program, Monash Biomedicine Discovery Institute, and Department of Biochemistry and Molecular Biology, Monash University, Victoria 3800, Australia.
Nuthasuda SrijakotreFrom the Cancer Program, Monash Biomedicine Discovery Institute, and Department of Biochemistry and Molecular Biology, Monash University, Victoria 3800, Australia.
Joey ManFrom the Cancer Program, Monash Biomedicine Discovery Institute, and Department of Biochemistry and Molecular Biology, Monash University, Victoria 3800, Australia.
Jessica VieusseuxFrom the Cancer Program, Monash Biomedicine Discovery Institute, and Department of Biochemistry and Molecular Biology, Monash University, Victoria 3800, Australia.
JoAnne E WatersFrom the Cancer Program, Monash Biomedicine Discovery Institute, and Department of Biochemistry and Molecular Biology, Monash University, Victoria 3800, Australia.
Yue Fengthe Centenary Institute of Cancer Medicine and Cell Biology, New South Wales 2050, Australia.
Charles G Baileythe Centenary Institute of Cancer Medicine and Cell Biology, New South Wales 2050, Australia, Sydney Medical School, University of Sydney, Sydney, New South Wales 2006, Australia.
John E J RaskoFrom the Cancer Program, Monash Biomedicine Discovery Institute, and Department of Biochemistry and Molecular Biology, Monash University, Victoria 3800, Australia, Sydney Medical School, University of Sydney, Sydney, New South Wales 2006, Australia, Cell and Molecular Therapies, Royal Prince Alfred Hospital, Camperdown, New South Wales 2050, Australia, and.
John T PriceFrom the Cancer Program, Monash Biomedicine Discovery Institute, and Department of Biochemistry and Molecular Biology, Monash University, Victoria 3800, Australia, the Centre for Chronic Disease, College of Health and Biomedicine, Victoria University, Victoria 8001, Australia.
Christina A MitchellFrom the Cancer Program, Monash Biomedicine Discovery Institute, and Department of Biochemistry and Molecular Biology, Monash University, Victoria 3800, Australia, christina.mitchell@monash.edu.
Monash University · AUCentenary Institute · AURoyal Prince Alfred Hospital · AUVictoria University · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

PtdIns(3,4,5)P3-dependent Rac exchanger 1 (PREX1) is a Rac-guanine nucleotide exchange factor (GEF) overexpressed in a significant proportion of human breast cancers that integrates signals from upstream ErbB2/3 and CXCR4 membrane surface receptors. However, the PREX1 domains that facilitate its oncogenic activity and downstream signaling are not completely understood. We identify that ERK1/2 MAPK acts downstream of PREX1 and contributes to PREX1-mediated anchorage-independent cell growth. PREX1 overexpression increased but its shRNA knockdown decreased ERK1/2 phosphorylation in response to EGF/IGF-1 stimulation, resulting in induction of the cell cycle regulators cyclin D1 and p21(WAF1/CIP1) PREX1-mediated ERK1/2 phosphorylation, anchorage-independent cell growth, and cell migration were suppressed by inhibition of MEK1/2/ERK1/2 signaling. PREX1 overexpression reduced staurosporine-induced apoptosis whereas its shRNA knockdown promoted apoptosis in response to staurosporine or the anti-estrogen drug tamoxifen. Expression of wild-type but not GEF-inactive PREX1 increased anchorage-independent cell growth. In addition, mouse xenograft studies revealed that expression of wild-type but not GEF-dead PREX1 resulted in the formation of larger tumors that displayed increased phosphorylation of ERK1/2 but not AKT. The impaired anchorage-independent cell growth, apoptosis, and ERK1/2 signaling observed in stable PREX1 knockdown cells was restored by expression of wild-type but not GEF-dead-PREX1. Therefore, PREX1-Rac-GEF activity is critical for PREX1-dependent anchorage-independent cell growth and xenograft tumor growth and may represent a possible therapeutic target for breast cancers that exhibit PREX1 overexpression.

Indexed as

Cell ProliferationGene Expression Regulation, NeoplasticMAP Kinase Signaling SystemAnimalsBreast NeoplasmsCyclin-Dependent Kinase Inhibitor p21FemaleGuanine Nucleotide Exchange FactorsHumansMAP Kinase Kinase 1MCF-7 CellsMiceMice, Inbred BALB CMice, NudeMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3CDKN1A protein, humanCyclin-Dependent Kinase Inhibitor p21Guanine Nucleotide Exchange FactorsMAPK1 protein, humanMAP Kinase Kinase 1Mitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3PREX1 protein, humanProto-Oncogene Proteins c-aktTamoxifenbreast cancercell migrationcell proliferationcell signalingERKguanine nucleotide exchange factor (GEF)

Identifiers

PMID27358402
PMCPMC5016125
OpenAlexW2507693146

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.