Evidence map›Paper›PMID 26304115›Full record

ArticleThe Journal of biological chemistry2015

The Alternative Splicing of Cytoplasmic Polyadenylation Element Binding Protein 2 Drives Anoikis Resistance and the Metastasis of Triple Negative Breast Cancer.

Ryan M Johnson, Ngoc T Vu, Brian P Griffin, Amanda E Gentry, Kellie J Archer, Charles E Chalfant, Margaret A Park

Abstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
–field-weighted citation impact
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

20 citing papers in PubMed.

  1. Review
  2. Article
  3. Skewing cPLAScience signaling · 2023
    Article
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  6. 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

7 authors.

Ryan M JohnsonFrom the Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond Virginia 23298.
Ngoc T VuFrom the Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond Virginia 23298, Vietnam Education Foundation, Arlington, Virginia 22201.
Brian P GriffinFrom the Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond Virginia 23298.
Amanda E GentryDepartment of Biostatistics, Virginia Commonwealth University, Richmond, Virginia 23298.
Kellie J ArcherDepartment of Biostatistics, Virginia Commonwealth University, Richmond, Virginia 23298, Virginia Commonwealth University Massey Cancer Center Biostatistics Shared Resource, Richmond, Virginia 23298, Center for the Study of Biological Complexity, Virginia Commonwealth University, Richmond, Virginia 23298.
Charles E ChalfantFrom the Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond Virginia 23298, Virginia Commonwealth University Massey Cancer Center Massey Cancer Center, Richmond, Virginia 23298, Research and Development, Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, Virginia 23224, Virginia Commonwealth University Institute of Molecular Medicine, Richmond Virginia, 23298, and Virginia Commonwealth University Johnson Center, Richmond, Virginia, 23298 cechalfant@vcu.edu.
Margaret A ParkFrom the Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond Virginia 23298, Virginia Commonwealth University Massey Cancer Center Massey Cancer Center, Richmond, Virginia 23298, mpark4@vcu.edu.

Funding

Virus Vector Shared ResourceP30CA016059 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI Keri R Maher · 1985 to 2026
$51.0M
Center for Clinical and Translational ResearchUL1TR000058 · NCATS · VIRGINIA COMMONWEALTH UNIVERSITY · PI MOELLER, FREDERICK GERARD · 2012 to 2015
$12.5M
The functional role of the cPLA2alpha/C1P interaction in sepsis resolutionR01HL125353 · NHLBI · VIRGINIA COMMONWEALTH UNIVERSITY · PI BROWN, RHODERICK E, CHALFANT, CHARLES E. · 2014 to 2018
$4.0M
Research Education in Statistical Genetics of Substance AbuseR25DA026119 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI NEALE, MICHAEL CHURTON · 2008 to 2018
$3.2M
Integration of Mixtures Toxicology, Toxicogenomics, and StatisticsT32ES007334 · NIEHS · VIRGINIA COMMONWEALTH UNIVERSITY · PI WHEELER, DAVID CHARLES · 2002 to 2018
$2.5M
Center for Clinical and Translational ResearchKL2TR000057 · NCATS · VIRGINIA COMMONWEALTH UNIVERSITY · PI MOELLER, FREDERICK GERARD · 2012 to 2014
$1.4M
Regulation of caspase 9 RNA splicing in NSCLC cancerR01CA154314 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI CHALFANT, CHARLES E. · 2011 to 2014
$1.2M
Informatic tools for predicting an ordinal response for high-dimensional dataR01LM011169 · NLM · VIRGINIA COMMONWEALTH UNIVERSITY · PI ARCHER, KELLIE J. · 2012 to 2015
$944k
The role of RNA splicing in non-small cell lung cancerI01BX001792 · VA · VA VETERANS ADMINISTRATION HOSPITAL · PI CHALFANT, CHARLES E. · 2013 to 2024
–
BLRD VA I01 BX001792NCATS NIH HHS 8KL2TR000057-03NCATS NIH HHS KL2 TR000057NCATS NIH HHS UL1 TR000058NCI NIH HHS 2P30 CA016059NCI NIH HHS CA154314NCI NIH HHS P30 CA016059NCI NIH HHS R01 CA154314NHLBI NIH HHS HL125353NHLBI NIH HHS R01 HL125353NIDA NIH HHS R25 DA026119NIEHS NIH HHS T32 ES007334NIEHS NIH HHS T32 ES07334NLM NIH HHS 1R01LM011169NLM NIH HHS R01 LM011169
6 · The paper itself

Abstract

Triple negative breast cancer (TNBC) represents an anomalous subset of breast cancer with a greatly reduced (30%) 5-year survival rate. The enhanced mortality and morbidity of TNBC arises from the high metastatic rate, which requires the acquisition of AnR, a process whereby anchorage-dependent cells become resistant to cell death induced by detachment. In this study TNBC cell lines were selected for AnR, and these cell lines demonstrated dramatic enhancement in the formation of lung metastases as compared with parental cells. Genetic analysis of the AnR subclones versus parental cells via next generation sequencing and analysis of global alternative RNA splicing identified that the mRNA splicing of cytoplasmic polyadenylation element binding 2 (CPEB2), a translational regulator, was altered in AnR TNBC cells. Specifically, increased inclusion of exon 4 into the mature mRNA to produce the CPEB2B isoform was observed in AnR cell lines. Molecular manipulations of CPEB2 splice variants demonstrated a key role for this RNA splicing event in the resistance of cells to anoikis. Specifically, down-regulation of the CPEB2B isoform using siRNA re-sensitized the AnR cell lines to detachment-induced cell death. The ectopic expression of CPEB2B in parental TNBC cell lines induced AnR and dramatically increased metastatic potential. Importantly, alterations in the alternative splicing of CPEB2 were also observed in human TNBC and additional subtypes of human breast cancer tumors linked to a high metastatic rate. Our findings demonstrate that the regulation of CPEB2 mRNA splicing is a key mechanism in AnR and a driving force in TNBC metastasis.

Indexed as

Alternative SplicingNeoplasm MetastasisAnimalsAnoikisCell Line, TumorFemaleHumansMiceMice, Inbred NODRNA-Binding ProteinsRNA, MessengerTriple Negative Breast NeoplasmsCPEB2 protein, humanRNA-Binding ProteinsRNA, Messengeralternative splicinganoikisbreast cancermetastasistranslation control

Identifiers

PMID26304115
PMCPMC4646214

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.