Evidence map›Paper›PMID 30898113›Full record

ArticleBMC cancer2019

Genome-wide CRISPR screen reveals PSMA6 to be an essential gene in pancreatic cancer cells.

Jesse Bakke, William C Wright, Anthony E Zamora, Peter Oladimeji, Jeremy Chase Crawford, Christopher T Brewer, Robert J Autry, William E Evans, Paul G Thomas, Taosheng Chen

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.7field-weighted citation impact, top 15% 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

15 citing papers in PubMed, 27 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. CRISPR Cas9 in Pancreatic Cancer Research.Frontiers in cell and developmental biology · 2019
    Review
  15. Review
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

10 authors at 1 institution in 1 country.

Jesse BakkeDepartment of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN, USA. Bakke2JL@cmich.edu.ORCID http://orcid.org/0000-0003-0305-5165
William C WrightDepartment of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN, USA.
Anthony E ZamoraDepartment of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Peter OladimejiDepartment of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN, USA.
Jeremy Chase CrawfordDepartment of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Christopher T BrewerDepartment of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN, USA.
Robert J AutryIntegrated Biomedical Sciences Program, University of Tennessee Health Science Center, Memphis, TN, USA.
William E EvansDepartment of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA.
Paul G ThomasDepartment of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Taosheng ChenDepartment of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN, USA. Taosheng.Chen@stjude.org.
St. Jude Children's Research Hospital · US

Funding

Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI CHARLES ROBERTS · 1985 to 2026
$166.9M
Regulation of xenobiotic receptors PXR and CAR: implications in drug dispositionR35GM118041 · NIGMS · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Taosheng Chen · 2016 to 2026
$4.3M
National Institutes of Health P30-CA21765National Institutes of Health R35-GM118041NCI NIH HHS P30 CA021765NIGMS NIH HHS R35 GM118041
6 · The paper itself

Abstract

backgroundDespite its relatively low incidence, pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer deaths because of the aggressive growth/metastasis of the tumor, the lack of early symptoms, and the poor treatment options. Basic research to identify potential therapeutic targets for PDAC is greatly needed.

methodsWe used a negative-selection genome-wide CRISPR screen to identify essential genes in the PANC-1 human pancreatic carcinoma cell line. We validated the top hits with follow-up siRNA screens, using the HPNE, HPAF-II, AsPC-1, and Mia PaCa-2 cell lines.

resultsThe PSMA6 gene was an identified candidate hit after the CRISPR screen, siRNA validation screen, and siRNA deconvolution screen. Spheroid formation assays and flow cytometry analysis showed that PSMA6 is critical for survival in many pancreatic ductal carcinoma cell models. Lastly, as PSMA6 protein is a proteosomal subunit of the 20S core complex, we showed that bortezomib, a proteasome inhibitor, was especially toxic in PANC-1 cells.

conclusionsFurther study of PSMA6 and the proteasome subunit that it encodes, along with other hits identified in our CRISPR screens, may provide valuable insights into potential therapeutic targets for PDAC.

Indexed as

BortezomibCarcinoma, Pancreatic DuctalCell Line, TumorCell ProliferationCell SurvivalClustered Regularly Interspaced Short Palindromic RepeatsGenome, HumanGenomicsHumansOncogenesPancreasPancreatic NeoplasmsProteasome Endopeptidase ComplexProteasome InhibitorsRNA, Small InterferingSpheroids, CellularBortezomibProteasome Endopeptidase ComplexProteasome InhibitorsPSMA6 protein, humanRNA, Small InterferingCRISPR screenEssential genesPancreatic cancerPDACPSMA6

Identifiers

PMID30898113
PMCPMC6429770
OpenAlexW2939720881

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.