Evidence map›Paper›PMID 26506596›Full record

ArticleOncotarget2015

A novel gammaretroviral shuttle vector insertional mutagenesis screen identifies SHARPIN as a breast cancer metastasis gene and prognostic biomarker.

Victor M Bii, Dustin T Rae, Grant D Trobridge

Abstract read
In one paragraph

Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing 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

16 citing papers in PubMed.

  1. Review
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  3. Article
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  5. Review
  6. Article
  7. Aberrant expression and high-frequency mutations ofExperimental and therapeutic medicine · 2019
    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

3 authors.

Victor M BiiWashington State University College of Pharmacy, WSU Spokane, Spokane, WA, USA.
Dustin T RaeWashington State University College of Pharmacy, WSU Spokane, Spokane, WA, USA.
Grant D TrobridgeWashington State University College of Pharmacy, WSU Spokane, Spokane, WA, USA.

Funding

Vector ProductionP01AI097100 · NIAID · SEATTLE CHILDREN'S HOSPITAL · PI BEARD, BRIAN C · 2012 to 2016
$11.9M
Improved Foamy Virus Vectors for AIDS Gene TherapyR01AI102672 · NIAID · WASHINGTON STATE UNIVERSITY · PI TROBRIDGE, GRANT D · 2013 to 2017
$1.8M
Mutagenesis Screen for Prostate CancerR15CA173598 · NCI · WASHINGTON STATE UNIVERSITY · PI TROBRIDGE, GRANT D · 2013 to 2013
$418k
NCI NIH HHS CA173598NCI NIH HHS R15 CA173598NIAID NIH HHS P01 AI097100NIAID NIH HHS R01 AI102672
6 · The paper itself

Abstract

Breast cancer (BC) is the second leading cause of malignancy among U.S. women. Metastasis results in a poor prognosis and increased mortality, but the molecular mechanisms by which metastatic tumors occur are not well understood. Identifying the genes that drive the metastatic process could provide targets for improved therapy and biomarkers to improve BC patient outcomes. Using a forward mutagenesis screen, BC cells mutagenized with a replication-incompetent gammaretroviral vector (γRV) were xenotransplanted into the mammary fat pad of immunodeficient mice. In this approach the vector provirus dysregulates nearby genes, providing a selective advantage to transduced cells to form metastases. Metastatic tumors were analyzed for proviral integration sites to identify nearby candidate metastasis genes. The γRV has a transgene cassette that allows for rescue in bacteria and rapid identification of vector integration sites. Using this approach, we identified the previously described metastasis gene WWTR1 (TAZ), and three other novel candidate metastasis genes including SHARPIN. SHARPIN was independently validated in vivo as a BC metastasis gene. Analysis of patient data showed that SHARPIN expression predicts metastasis-free survival after adjuvant therapy. Our approach has broad potential to identify genes involved in oncogenic processes for BC and other cancers. We show here it can identify both known (WWTR1) and novel (SHARPIN) BC metastasis genes.

Indexed as

Mutagenesis, InsertionalAnimalsBase SequenceBiomarkers, TumorBreast NeoplasmsCell Line, TumorGammaretrovirusGene Expression Regulation, NeoplasticGenetic VectorsHumansIntracellular Signaling Peptides and ProteinsKaplan-Meier EstimateMolecular Sequence DataNeoplasm MetastasisPrognosisRNA InterferenceBiomarkers, TumorIntracellular Signaling Peptides and ProteinsSHARPIN protein, humanTrans-ActivatorsTranscriptional Coactivator with PDZ-Binding Motif ProteinsTranscription FactorsUbiquitinsWWTR1 protein, humanbreast cancerChromosome Sectiongammaretroviral vector (γRV)insertional mutagenesis screenmetastasisprognostic biomarker

Identifiers

PMID26506596
PMCPMC4741842

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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.